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Study of Binimetinib + Nivolumab Plus or Minus Ipilimumab in Patients With Previously Treated Microsatellite-stable (MSS) Metastatic Colorectal Cancer With RAS Mutation

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ClinicalTrials.gov Identifier: NCT03271047
Recruitment Status : Completed
First Posted : September 1, 2017
Results First Posted : November 2, 2021
Last Update Posted : January 4, 2022
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions MSS
RAS-mutant Colorectal Cancer
Interventions Drug: binimetinib
Drug: nivolumab
Drug: ipilimumab
Enrollment 75
Recruitment Details  
Pre-assignment Details This study included 2 phases: Phase 1b and Phase 2. The recommended dose for Phase 2 (RP2D) of binimetinib was determined in Phase 1b (dose finding phase).
Arm/Group Title Phase 1b: Nivolumab+Binimetinib Phase 1b: Nivolumab+Ipilimumab+Binimetinib Phase 2: Nivolumab+Binimetinib Phase 2: Nivolumab+Ipilimumab+Binimetinib
Hide Arm/Group Description Participants with previously treated microsatellite-stable (MSS) metastatic colorectal cancer with rat sarcoma virus (RAS) mutation received binimetinib at a starting dose of 45 milligrams (mg) tablet orally twice daily (BID) along with 480 mg intravenously (IV) dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 milligram per kilogram (mg/kg) IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
Period Title: Phase 1b: Dose Finding Period
Started 10 11 0 0
Completed 0 0 0 0
Not Completed 10 11 0 0
Reason Not Completed
Death             8             8             0             0
Lost to Follow-up             1             0             0             0
Withdrawal by Subject             0             2             0             0
Completed follow-up per protocol             1             1             0             0
Period Title: Randomized Phase 2 Period
Started 0 0 27 [1] 27 [1]
Completed 0 0 0 0
Not Completed 0 0 27 27
Reason Not Completed
Other             0             0             0             1
Death             0             0             20             21
Lost to Follow-up             0             0             2             1
Withdrawal by Subject             0             0             5             0
Completed follow-up per protocol             0             0             0             4
[1]
Participants randomized to Phase 2 of the study.
Arm/Group Title Phase 1b: Nivolumab+Binimetinib Phase 1b: Nivolumab+Ipilimumab+Binimetinib Phase 2: Nivolumab+Binimetinib Phase 2: Nivolumab+Ipilimumab+Binimetinib Total
Hide Arm/Group Description Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. Total of all reporting groups
Overall Number of Baseline Participants 10 11 27 27 75
Hide Baseline Analysis Population Description
Full Analysis Set (FAS) included all participants who received at least 1 dose of any study drug in Phase 1b and all participants randomized to study treatment in Phase 2.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 11 participants 27 participants 27 participants 75 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
5
  50.0%
9
  81.8%
19
  70.4%
20
  74.1%
53
  70.7%
>=65 years
5
  50.0%
2
  18.2%
8
  29.6%
7
  25.9%
22
  29.3%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 11 participants 27 participants 27 participants 75 participants
Female
2
  20.0%
4
  36.4%
11
  40.7%
10
  37.0%
27
  36.0%
Male
8
  80.0%
7
  63.6%
16
  59.3%
17
  63.0%
48
  64.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 11 participants 27 participants 27 participants 75 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
1
   3.7%
0
   0.0%
1
   1.3%
Not Hispanic or Latino
10
 100.0%
11
 100.0%
21
  77.8%
23
  85.2%
65
  86.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
5
  18.5%
4
  14.8%
9
  12.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 11 participants 27 participants 27 participants 75 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
1
   3.7%
0
   0.0%
1
   1.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
  10.0%
0
   0.0%
1
   3.7%
1
   3.7%
3
   4.0%
White
9
  90.0%
11
 100.0%
21
  77.8%
23
  85.2%
64
  85.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
4
  14.8%
3
  11.1%
7
   9.3%
1.Primary Outcome
Title Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLT)
Hide Description DLT:Adverse event(AE)/abnormal laboratory assessed unrelated-disease,disease progression,intercurrent illness/concomitant medication/therapies resulting inability tolerate 75% dose intensity in Cycle 1.Total bilirubin(TBL)grade(G)>=3 (>3.0*upper limit of normal[ULN)]);AST/ALT>5-8*ULN>5 days,>8*ULN,>3*ULN concurrent TBL>2*ULN;G>=3 serum creatinine,CK elevation,ECG QTcF prolonged,G3 troponin,electrolyte>72 hours,G3/4 amylase/lipase.G4 ANC,platelet count>7 days;G3/4 platelet count,other AE except lymphopenia.G>=3 retinopathy,other disorder>21 days;G2 uveitis/eye pain/blurred vision/decreased visual acuity;G4 other disorder.Decrease LVEF>10% G>=3 cardiac disorders.G3/4 hypertension.G3 fatigue>=7 days,hypersensitivity,infusion reaction,fever>=72 hours/hemodynamic compromise,endocrinopathy.G>=2 interstitial lung disease/pneumonitis;G3 bronchospasm.G3/4 rash,hand foot skin reaction,photosensitivity.G3 colitis;G3/4 diarrhea,nausea/vomiting.Neurologic G3.Other hematologic/nonhematolic G>=3 AE.
Time Frame Cycle 1: Day 1 up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Dose-Determining Set (DDS) included all participants in Phase 1b who experienced a DLT or receive at least 75% of the planned binimetinib dose intensity during Cycle 1.
Arm/Group Title Phase 1b: Nivolumab+Binimetinib Phase 1b: Nivolumab+Ipilimumab+Binimetinib
Hide Arm/Group Description:
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Overall Number of Participants Analyzed 9 11
Measure Type: Count of Participants
Unit of Measure: Participants
1
  11.1%
2
  18.2%
2.Primary Outcome
Title Phase 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
Hide Description ORR was defined as the percentage of participants who achieved a best overall response (BOR) of complete response (CR) or partial response (PR) as determined by investigator per RECIST v1.1. As per RECIST v1.1, CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (<)10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-progressive disease (PD). PD was defined as at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was considered progression.
Time Frame From start of the treatment until disease progression, death or initiation of new anticancer therapy, whichever occurred first (Phase 2: maximum up to 26 months approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized to study treatment in Phase 2.
Arm/Group Title Phase 2: Nivolumab+Binimetinib Phase 2: Nivolumab+Ipilimumab+Binimetinib
Hide Arm/Group Description:
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
Overall Number of Participants Analyzed 27 27
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
0.0 [1] 
(NA to NA)
7.4
(0.9 to 24.3)
[1]
Upper and lower limit of 95% confidence interval were not estimable, as there were no participants who had event in this reporting group.
3.Secondary Outcome
Title Phase 1b: Objective Response Rate (ORR) Per RECIST v1.1
Hide Description ORR was defined as the percentage of participants who achieved a BOR of CR or PR as determined by investigator per RECIST v1.1. As per RECIST v1.1, CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. PR was defined as at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the baseline sum of diameters. Non-target lesions must be non-PD. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Time Frame From start of the treatment until disease progression, death or initiation of new anticancer therapy, whichever occurred first (Phase 1b: maximum up to 9 months approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of any study treatment in Phase 1b.
Arm/Group Title Phase 1b: Nivolumab+Binimetinib Phase 1b: Nivolumab+Ipilimumab+Binimetinib
Hide Arm/Group Description:
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Overall Number of Participants Analyzed 10 11
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
0.0 [1] 
(NA to NA)
0.0 [1] 
(NA to NA)
[1]
Upper and lower limit of 95% confidence interval were not estimable, as there were no participants who had event in this reporting group.
4.Secondary Outcome
Title Duration of Response (DOR) as Per RECIST v1.1
Hide Description DOR was defined as the time between the date of the first documented confirmed response (PR or CR) and the date of the first documented progression or death due to any cause. As per RECIST v1.1: CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes short axis measures <10 mm. PR was defined as at least 30% decrease in sum of measures (tumor lesions- longest diameter and nodes- short axis) of target lesions, taking as reference baseline sum of diameters. PD was defined as at least 20% increase in sum of diameters of measured lesions taking as references smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion. Unequivocal progression of existing non-target lesions.
Time Frame From date of first documented CR/PR to date of first documented PD, death or initiation of new anticancer therapy, whichever occurred first (Phase 1b: maximum up to 9 months approximately, Phase 2: maximum up to 26 months approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who received at least 1 dose of any study drug in Phase 1b and all participants randomized to study treatment in Phase 2. Here, "Overall Number of Participants Analyzed" signifies number of participants who achieved an objective response. There were no participants who had event in Phase 1b and Nivolumab and Binimetinib group of Phase 2.
Arm/Group Title Phase 1b: Nivolumab+Binimetinib Phase 1b: Nivolumab+Ipilimumab+Binimetinib Phase 2: Nivolumab+Binimetinib Phase 2: Nivolumab+Ipilimumab+Binimetinib
Hide Arm/Group Description:
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
Overall Number of Participants Analyzed 0 0 0 2
Median (95% Confidence Interval)
Unit of Measure: Months
11.4
(7.5 to 15.2)
5.Secondary Outcome
Title Percentage of Participants With Complete Response as Per RECIST v1.1
Hide Description Complete response as per RECIST v1.1 was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm.
Time Frame From start of the treatment until disease progression, death or initiation of new anticancer therapy, whichever occurred first (Phase 1b: maximum up to 9 months approximately and Phase 2: maximum up to 26 months approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who received at least 1 dose of any study drug in Phase 1b and all participants randomized to study treatment in Phase 2.
Arm/Group Title Phase 1b: Nivolumab+Binimetinib Phase 1b: Nivolumab+Ipilimumab+Binimetinib Phase 2: Nivolumab+Binimetinib Phase 2: Nivolumab+Ipilimumab+Binimetinib
Hide Arm/Group Description:
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
Overall Number of Participants Analyzed 10 11 27 27
Measure Type: Number
Unit of Measure: Percentage of participants
0 0 0 0
6.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAE) Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03
Hide Description AE: any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE: AE resulting in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs: events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy minus 1 day, whichever occurred first. TEAE graded by CTCAE grade 4.03: Grade 3: severe/medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care activities of daily living (ADL); Grade 4: life-threatening consequence, urgent intervention indicated. In this outcome measure, number of participants with 'all grades' and 'Grade 3/4' were reported.
Time Frame From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (Phase 1b: maximum up to 9 months approximately and Phase 2: maximum up to 26 months approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety set included of all participants who received at least 1 dose of study drug.
Arm/Group Title Phase 1b: Nivolumab+Binimetinib Phase 1b: Nivolumab+Ipilimumab+Binimetinib Phase 2: Nivolumab+Binimetinib Phase 2: Nivolumab+Ipilimumab+Binimetinib
Hide Arm/Group Description:
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
Overall Number of Participants Analyzed 10 11 27 27
Measure Type: Count of Participants
Unit of Measure: Participants
Treatment emergent AEs- All grades
10
 100.0%
11
 100.0%
27
 100.0%
27
 100.0%
Treatment emergent SAEs- All grades
5
  50.0%
6
  54.5%
12
  44.4%
11
  40.7%
Treatment emergent AEs- Grade 3/4
6
  60.0%
8
  72.7%
19
  70.4%
21
  77.8%
Treatment emergent SAEs- Grade 3/4
5
  50.0%
6
  54.5%
11
  40.7%
10
  37.0%
7.Secondary Outcome
Title Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03: Hematology and Coagulation
Hide Description Hematological parameters included: Hemoglobin graded high, Hemoglobin graded low, Platelets count graded low, White Blood Cell (WBC) graded high, WBC graded low, Neutrophils graded low, Lymphocytes graded high, Lymphocytes graded low. Coagulation parameters included: International Normalized Ratio (INR) graded high, Activated Partial Thromboplastin Time (aPTT) graded high. Test abnormalities were graded by CTCAE v4.03 as Grade 1=mild; Grade 2=moderate; Grade 3/Grade 4=severe/life-threatening. A grade 0 was assigned for all non-missing values not graded as 1 or higher. If value was graded >=1 but falls within the normal range, the grade was reset to 0. Categories with at least 1 non-zero data values are reported.
Time Frame Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately)
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Hide Analysis Population Description
Safety set included of all participants who received at least 1 dose of study drug. Here "Number Analyzed" signifies number of participants evaluable for specified rows.
Arm/Group Title Phase 1b: Nivolumab+Binimetinib Phase 1b: Nivolumab+Ipilimumab+Binimetinib Phase 2: Nivolumab+Binimetinib Phase 2: Nivolumab+Ipilimumab+Binimetinib
Hide Arm/Group Description:
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
Overall Number of Participants Analyzed 10 11 27 27
Measure Type: Count of Participants
Unit of Measure: Participants
Hemoglobin- CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 7 participants 6 participants 13 participants 16 participants
3
  42.9%
3
  50.0%
4
  30.8%
5
  31.3%
Hemoglobin- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 7 participants 6 participants 13 participants 16 participants
2
  28.6%
2
  33.3%
6
  46.2%
10
  62.5%
Hemoglobin- CTCAE Graded Low: Grade 0 (at baseline) to Grade 2 (at post baseline) Number Analyzed 7 participants 6 participants 13 participants 16 participants
2
  28.6%
1
  16.7%
2
  15.4%
1
   6.3%
Hemoglobin- CTCAE Graded Low: Grade 0 (at baseline) to Grade 3 (at post baseline) Number Analyzed 7 participants 6 participants 13 participants 16 participants
0
   0.0%
0
   0.0%
1
   7.7%
0
   0.0%
Hemoglobin- CTCAE Graded Low: Grade 1 (at baseline) to Grade 0 (at post baseline) Number Analyzed 3 participants 5 participants 10 participants 6 participants
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
Hemoglobin- CTCAE Graded Low: Grade 1 (at baseline) to Grade 1 (at post baseline) Number Analyzed 3 participants 5 participants 10 participants 6 participants
1
  33.3%
4
  80.0%
4
  40.0%
4
  66.7%
Hemoglobin- CTCAE Graded Low: Grade 1 (at baseline) to Grade 2 (at post baseline) Number Analyzed 3 participants 5 participants 10 participants 6 participants
2
  66.7%
0
   0.0%
3
  30.0%
1
  16.7%
Hemoglobin- CTCAE Graded Low: Grade 1 (at baseline) to Grade 3 (at post baseline) Number Analyzed 3 participants 5 participants 10 participants 6 participants
0
   0.0%
1
  20.0%
1
  10.0%
1
  16.7%
Hemoglobin- CTCAE Graded Low: Grade 1 (at baseline) to Missing (at post baseline) Number Analyzed 3 participants 5 participants 10 participants 6 participants
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
Hemoglobin- CTCAE Graded Low: Grade 2 (at baseline) to Grade 2 (at post baseline) Number Analyzed 0 participants 0 participants 4 participants 5 participants
3
  75.0%
5
 100.0%
Hemoglobin- CTCAE Graded Low: Grade 2 (at baseline) to Grade 3 (at post baseline) Number Analyzed 0 participants 0 participants 4 participants 5 participants
1
  25.0%
0
   0.0%
Hemoglobin- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 27 participants
10
 100.0%
11
 100.0%
26
  96.3%
26
  96.3%
Hemoglobin- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 27 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.7%
Hemoglobin- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) Number Analyzed 10 participants 10 participants 27 participants 27 participants
0
   0.0%
0
   0.0%
1
   3.7%
0
   0.0%
Lymphocytes - CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 7 participants 9 participants 21 participants 22 participants
6
  85.7%
7
  77.8%
11
  52.4%
11
  50.0%
Lymphocytes- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 7 participants 9 participants 21 participants 22 participants
0
   0.0%
0
   0.0%
2
   9.5%
4
  18.2%
Lymphocytes- CTCAE Graded Low: Grade 0 (at baseline) to Grade 2 (at post baseline) Number Analyzed 7 participants 9 participants 21 participants 22 participants
0
   0.0%
2
  22.2%
4
  19.0%
6
  27.3%
Lymphocytes- CTCAE Graded Low: Grade 0 (at baseline) to Grade 3 (at post baseline) Number Analyzed 7 participants 9 participants 21 participants 22 participants
1
  14.3%
0
   0.0%
3
  14.3%
1
   4.5%
Lymphocytes- CTCAE Graded Low: Grade 0 (at baseline) to Missing (at post baseline) Number Analyzed 7 participants 9 participants 21 participants 22 participants
0
   0.0%
0
   0.0%
1
   4.8%
0
   0.0%
Lymphocytes- CTCAE Graded Low: Grade 1 (at baseline) to Grade 0 (at post baseline) Number Analyzed 0 participants 1 participants 2 participants 1 participants
0
   0.0%
0
   0.0%
1
 100.0%
Lymphocytes- CTCAE Graded Low: Grade 1 (at baseline) to Grade 2 (at post baseline) Number Analyzed 0 participants 1 participants 2 participants 1 participants
1
 100.0%
1
  50.0%
0
   0.0%
Lymphocytes- CTCAE Graded Low: Grade 1 (at baseline) to Grade 3 (at post baseline) Number Analyzed 0 participants 1 participants 2 participants 1 participants
0
   0.0%
1
  50.0%
0
   0.0%
Lymphocytes- CTCAE Graded Low: Grade 2 (at baseline) to Grade 0 (at post baseline) Number Analyzed 2 participants 0 participants 3 participants 4 participants
0
   0.0%
1
  33.3%
0
   0.0%
Lymphocytes- CTCAE Graded Low: Grade 2 (at baseline) to Grade 2 (at post baseline) Number Analyzed 2 participants 0 participants 3 participants 4 participants
1
  50.0%
1
  33.3%
2
  50.0%
Lymphocytes- CTCAE Graded Low: Grade 2 (at baseline) to Grade 3 (at post baseline) Number Analyzed 2 participants 0 participants 3 participants 4 participants
1
  50.0%
1
  33.3%
2
  50.0%
Lymphocytes- CTCAE Graded Low: Grade 3 (at baseline) to Grade 0 (at post baseline) Number Analyzed 1 participants 1 participants 1 participants 0 participants
0
   0.0%
0
   0.0%
1
 100.0%
Lymphocytes- CTCAE Graded Low: Grade 3 (at baseline) to Grade 2 (at post baseline) Number Analyzed 1 participants 1 participants 1 participants 0 participants
0
   0.0%
1
 100.0%
0
   0.0%
Lymphocytes- CTCAE Graded Low: Grade 3 (at baseline) to Grade 3 (at post baseline) Number Analyzed 1 participants 1 participants 1 participants 0 participants
1
 100.0%
0
   0.0%
0
   0.0%
Lymphocytes- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 27 participants
9
  90.0%
11
 100.0%
25
  92.6%
26
  96.3%
Lymphocytes- CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 27 participants
1
  10.0%
0
   0.0%
1
   3.7%
1
   3.7%
Lymphocytes- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 27 participants
0
   0.0%
0
   0.0%
1
   3.7%
0
   0.0%
Neutrophils- CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 10 participants 11 participants 25 participants 27 participants
9
  90.0%
11
 100.0%
23
  92.0%
26
  96.3%
Neutrophils- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 10 participants 11 participants 25 participants 27 participants
0
   0.0%
0
   0.0%
1
   4.0%
1
   3.7%
Neutrophils- CTCAE Graded Low: Grade 0 (at baseline) to Grade 2 (at post baseline) Number Analyzed 10 participants 11 participants 25 participants 27 participants
1
  10.0%
0
   0.0%
0
   0.0%
0
   0.0%
Neutrophils- CTCAE Graded Low: Grade 0 (at baseline) to Missing (at post baseline) Number Analyzed 10 participants 11 participants 25 participants 27 participants
0
   0.0%
0
   0.0%
1
   4.0%
0
   0.0%
Neutrophils- CTCAE Graded Low: Grade 1 (at baseline) to Grade 0 (at post baseline) Number Analyzed 0 participants 0 participants 2 participants 0 participants
1
  50.0%
Neutrophils- CTCAE Graded Low: Grade 1 (at baseline) to Grade 3 (at post baseline) Number Analyzed 0 participants 0 participants 2 participants 0 participants
1
  50.0%
Platelets- CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 10 participants 10 participants 26 participants 26 participants
8
  80.0%
9
  90.0%
21
  80.8%
22
  84.6%
Platelets- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 10 participants 10 participants 26 participants 26 participants
2
  20.0%
1
  10.0%
3
  11.5%
4
  15.4%
Platelets- CTCAE Graded Low: Grade 0 (at baseline) to Missing (at post baseline) Number Analyzed 10 participants 10 participants 26 participants 26 participants
0
   0.0%
0
   0.0%
2
   7.7%
0
   0.0%
Platelets- CTCAE Graded Low: Grade 1 (at baseline) to Grade 0 (at post baseline) Number Analyzed 0 participants 1 participants 1 participants 1 participants
1
 100.0%
0
   0.0%
0
   0.0%
Platelets- CTCAE Graded Low: Grade 1 (at baseline) to Grade 1 (at post baseline) Number Analyzed 0 participants 1 participants 1 participants 1 participants
0
   0.0%
1
 100.0%
1
 100.0%
WBC- CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 10 participants 11 participants 26 participants 26 participants
9
  90.0%
11
 100.0%
21
  80.8%
24
  92.3%
WBC- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 10 participants 11 participants 26 participants 26 participants
0
   0.0%
0
   0.0%
2
   7.7%
0
   0.0%
WBC- CTCAE Graded Low: Grade 0 (at baseline) to Grade 2 (at post baseline) Number Analyzed 10 participants 11 participants 26 participants 26 participants
1
  10.0%
0
   0.0%
1
   3.8%
2
   7.7%
WBC- CTCAE Graded Low: Grade 0 (at baseline) to Grade 4 (at post baseline) Number Analyzed 10 participants 11 participants 26 participants 26 participants
0
   0.0%
0
   0.0%
1
   3.8%
0
   0.0%
WBC- CTCAE Graded Low: Grade 0 (at baseline) to Missing (at post baseline) Number Analyzed 10 participants 11 participants 26 participants 26 participants
0
   0.0%
0
   0.0%
1
   3.8%
0
   0.0%
WBC- CTCAE Graded Low: Grade 1 (at baseline) to Grade 1 (at post baseline) Number Analyzed 0 participants 0 participants 1 participants 1 participants
1
 100.0%
0
   0.0%
WBC- CTCAE Graded Low: Grade 1 (at baseline) to Grade 2 (at post baseline) Number Analyzed 0 participants 0 participants 1 participants 1 participants
0
   0.0%
1
 100.0%
WBC- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 27 participants
10
 100.0%
11
 100.0%
26
  96.3%
27
 100.0%
WBC- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 27 participants
0
   0.0%
0
   0.0%
1
   3.7%
0
   0.0%
aPTT- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 10 participants 10 participants 24 participants 24 participants
6
  60.0%
8
  80.0%
16
  66.7%
17
  70.8%
aPTT- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 10 participants 10 participants 24 participants 24 participants
3
  30.0%
2
  20.0%
6
  25.0%
6
  25.0%
aPTT- CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) Number Analyzed 10 participants 10 participants 24 participants 24 participants
1
  10.0%
0
   0.0%
2
   8.3%
1
   4.2%
aPTT- CTCAE Graded High: Grade 1 (at baseline) to Grade 0 (at post baseline) Number Analyzed 0 participants 1 participants 3 participants 2 participants
0
   0.0%
0
   0.0%
1
  50.0%
aPTT- CTCAE Graded High: Grade 1 (at baseline) to Grade 1 (at post baseline) Number Analyzed 0 participants 1 participants 3 participants 2 participants
1
 100.0%
1
  33.3%
1
  50.0%
aPTT- CTCAE Graded High: Grade 1 (at baseline) to Grade 3 (at post baseline) Number Analyzed 0 participants 1 participants 3 participants 2 participants
0
   0.0%
1
  33.3%
0
   0.0%
aPTT- CTCAE Graded High: Grade 1 (at baseline) to Missing (at post baseline) Number Analyzed 0 participants 1 participants 3 participants 2 participants
0
   0.0%
1
  33.3%
0
   0.0%
aPTT- CTCAE Graded High: Missing (at baseline) to Grade 0 (at post baseline) Number Analyzed 0 participants 0 participants 0 participants 1 participants
1
 100.0%
INR- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 9 participants 8 participants 20 participants 17 participants
5
  55.6%
6
  75.0%
16
  80.0%
13
  76.5%
INR- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 9 participants 8 participants 20 participants 17 participants
4
  44.4%
2
  25.0%
4
  20.0%
4
  23.5%
INR- CTCAE Graded High: Grade 1 (at baseline) to Grade 0 (at post baseline) Number Analyzed 1 participants 2 participants 7 participants 9 participants
0
   0.0%
1
  50.0%
1
  14.3%
1
  11.1%
INR- CTCAE Graded High: Grade 1 (at baseline) to Grade 1 (at post baseline) Number Analyzed 1 participants 2 participants 7 participants 9 participants
1
 100.0%
1
  50.0%
5
  71.4%
8
  88.9%
INR- CTCAE Graded High: Grade 1 (at baseline) to Missing (at post baseline) Number Analyzed 1 participants 2 participants 7 participants 9 participants
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
INR- CTCAE Graded High: Grade 2 (at baseline) to Grade 2 (at post baseline) Number Analyzed 0 participants 1 participants 0 participants 0 participants
1
 100.0%
INR- CTCAE Graded High: Missing (at baseline) to Grade 0 (at post baseline) Number Analyzed 0 participants 0 participants 0 participants 1 participants
1
 100.0%
8.Secondary Outcome
Title Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on Normal Range: Hematology and Coagulation
Hide Description Hematology parameters: Basophils, Eosinophils, Hematocrit, Monocytes, Red blood cells (RBC). Coagulation parameters: Prothrombin Time. Laboratory values were as per laboratory normal ranges. Values above range were reported as high and values below range as low. Laboratory parameters were graded based on laboratory normal ranges as low, normal, high and missing are reported in this outcome measure. Categories with at least 1 non-zero data values are reported.
Time Frame Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set included of all participants who received at least 1 dose of study drug. Here "Number Analyzed" signifies number of participants evaluable for specified rows.
Arm/Group Title Phase 1b: Nivolumab+Binimetinib Phase 1b: Nivolumab+Ipilimumab+Binimetinib Phase 2: Nivolumab+Binimetinib Phase 2: Nivolumab+Ipilimumab+Binimetinib
Hide Arm/Group Description:
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
Overall Number of Participants Analyzed 10 11 27 27
Measure Type: Count of Participants
Unit of Measure: Participants
Basophils: Normal (at baseline) to Low (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 27 participants
0
   0.0%
0
   0.0%
1
   3.7%
0
   0.0%
Basophils: Normal (at baseline) to Normal (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 27 participants
10
 100.0%
11
 100.0%
25
  92.6%
27
 100.0%
Basophils: Normal (at baseline) to Missing (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 27 participants
0
   0.0%
0
   0.0%
1
   3.7%
0
   0.0%
Eosinophils: Normal (at baseline) to Low (at post baseline) Number Analyzed 9 participants 11 participants 27 participants 27 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.7%
Eosinophils: Normal (at baseline) to Normal (at post baseline) Number Analyzed 9 participants 11 participants 27 participants 27 participants
7
  77.8%
11
 100.0%
25
  92.6%
20
  74.1%
Eosinophils: Normal (at baseline) to High (at post baseline) Number Analyzed 9 participants 11 participants 27 participants 27 participants
2
  22.2%
0
   0.0%
1
   3.7%
6
  22.2%
Eosinophils: Normal (at baseline) to Missing (at post baseline) Number Analyzed 9 participants 11 participants 27 participants 27 participants
0
   0.0%
0
   0.0%
1
   3.7%
0
   0.0%
Eosinophils: High (at baseline) to Normal (at post baseline) Number Analyzed 1 participants 0 participants 0 participants 0 participants
1
 100.0%
Hematocrit: Low (at baseline) to Low (at post baseline) Number Analyzed 2 participants 2 participants 10 participants 9 participants
2
 100.0%
1
  50.0%
8
  80.0%
9
 100.0%
Hematocrit: Low (at baseline) to Normal (at post baseline) Number Analyzed 2 participants 2 participants 10 participants 9 participants
0
   0.0%
1
  50.0%
1
  10.0%
0
   0.0%
Hematocrit: Low (at baseline) to Missing (at post baseline) Number Analyzed 2 participants 2 participants 10 participants 9 participants
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
Hematocrit: Normal (at baseline) to Low (at post baseline) Number Analyzed 8 participants 9 participants 17 participants 18 participants
5
  62.5%
4
  44.4%
13
  76.5%
12
  66.7%
Hematocrit: Normal (at baseline) to Normal (at post baseline) Number Analyzed 8 participants 9 participants 17 participants 18 participants
3
  37.5%
4
  44.4%
4
  23.5%
6
  33.3%
Hematocrit: Normal (at baseline) to High & Low (at post baseline) Number Analyzed 8 participants 9 participants 17 participants 18 participants
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
Monocytes: Normal (at baseline) to Low (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 26 participants
1
  10.0%
0
   0.0%
1
   3.7%
0
   0.0%
Monocytes: Normal (at baseline) to Normal (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 26 participants
9
  90.0%
7
  63.6%
19
  70.4%
20
  76.9%
Monocytes: Normal (at baseline) to High (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 26 participants
0
   0.0%
4
  36.4%
6
  22.2%
6
  23.1%
Monocytes: Normal (at baseline) to Missing (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 26 participants
0
   0.0%
0
   0.0%
1
   3.7%
0
   0.0%
Monocytes: High (at baseline) to Normal (at post baseline) Number Analyzed 0 participants 0 participants 0 participants 1 participants
1
 100.0%
RBC: Low (at baseline) to Low (at post baseline) Number Analyzed 1 participants 2 participants 14 participants 7 participants
1
 100.0%
1
  50.0%
13
  92.9%
6
  85.7%
RBC: Low (at baseline) to Normal (at post baseline) Number Analyzed 1 participants 2 participants 14 participants 7 participants
0
   0.0%
1
  50.0%
1
   7.1%
1
  14.3%
RBC: Normal (at baseline) to Low (at post baseline) Number Analyzed 8 participants 9 participants 13 participants 19 participants
6
  75.0%
5
  55.6%
8
  61.5%
10
  52.6%
RBC: Normal (at baseline) to Normal (at post baseline) Number Analyzed 8 participants 9 participants 13 participants 19 participants
2
  25.0%
4
  44.4%
3
  23.1%
9
  47.4%
RBC: Normal (at baseline) to High (at post baseline) Number Analyzed 8 participants 9 participants 13 participants 19 participants
0
   0.0%
0
   0.0%
1
   7.7%
0
   0.0%
RBC: Normal (at baseline) to Missing (at post baseline) Number Analyzed 8 participants 9 participants 13 participants 19 participants
0
   0.0%
0
   0.0%
1
   7.7%
0
   0.0%
RBC: High (at baseline) to Low (at post baseline) Number Analyzed 1 participants 0 participants 0 participants 1 participants
0
   0.0%
1
 100.0%
RBC: High (at baseline) to Normal (at post baseline) Number Analyzed 1 participants 0 participants 0 participants 1 participants
1
 100.0%
0
   0.0%
Prothrombin Time: Normal (at baseline) to Normal (at post baseline) Number Analyzed 7 participants 7 participants 19 participants 17 participants
3
  42.9%
3
  42.9%
8
  42.1%
8
  47.1%
Prothrombin Time: Normal (at baseline) to High (at post baseline) Number Analyzed 7 participants 7 participants 19 participants 17 participants
4
  57.1%
4
  57.1%
11
  57.9%
9
  52.9%
Prothrombin Time: High (at baseline) to Normal (at post baseline) Number Analyzed 3 participants 4 participants 8 participants 9 participants
0
   0.0%
1
  25.0%
0
   0.0%
0
   0.0%
Prothrombin Time: High (at baseline) to High (at post baseline) Number Analyzed 3 participants 4 participants 8 participants 9 participants
3
 100.0%
3
  75.0%
7
  87.5%
9
 100.0%
Prothrombin Time: High (at baseline) to Missing (at post baseline) Number Analyzed 3 participants 4 participants 8 participants 9 participants
0
   0.0%
0
   0.0%
1
  12.5%
0
   0.0%
Prothrombin Time: Missing (at baseline) to High (at post baseline) Number Analyzed 0 participants 0 participants 0 participants 1 participants
1
 100.0%
9.Secondary Outcome
Title Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on CTCAE v4.03: Chemistry
Hide Description Abnormalities: Albumin graded low, Alkaline phosphatase (ALP) graded high, Alanine aminotransferase (ALT) graded high, Aspartate aminotransferase (AST) graded high, Bilirubin graded high, Amylase graded high, Creatinine graded high, Corrected calcium graded high, Creatine Kinase (CK) graded high, Glucose graded high, Glucose graded low, Lipase graded high, Magnesium graded high, Magnesium graded low, Potassium graded high, Potassium graded low, Sodium graded high and Sodium graded low. Test abnormalities were graded by CTCAE v4.03 as Grade 1=mild; Grade 2=moderate; Grade 3/Grade 4=severe/life-threatening. A grade 0 was assigned for all non-missing values not graded as 1 or higher. If value was graded >=1 but falls within the normal range, the grade was reset to 0. Categories with at least 1 non-zero data values are reported.
Time Frame Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set included of all participants who received at least 1 dose of study drug. Here "Number Analyzed" signifies number of participants evaluable for specified rows.
Arm/Group Title Phase 1b: Nivolumab+Binimetinib Phase 1b: Nivolumab+Ipilimumab+Binimetinib Phase 2: Nivolumab+Binimetinib Phase 2: Nivolumab+Ipilimumab+Binimetinib
Hide Arm/Group Description:
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
Overall Number of Participants Analyzed 10 11 27 27
Measure Type: Count of Participants
Unit of Measure: Participants
ALT- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 8 participants 10 participants 20 participants 21 participants
5
  62.5%
5
  50.0%
12
  60.0%
12
  57.1%
ALT- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 8 participants 10 participants 20 participants 21 participants
3
  37.5%
5
  50.0%
7
  35.0%
5
  23.8%
ALT- CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) Number Analyzed 8 participants 10 participants 20 participants 21 participants
0
   0.0%
0
   0.0%
1
   5.0%
1
   4.8%
ALT- CTCAE Graded High: Grade 0 (at baseline) to Grade 3 (at post baseline) Number Analyzed 8 participants 10 participants 20 participants 21 participants
0
   0.0%
0
   0.0%
0
   0.0%
3
  14.3%
ALT- CTCAE Graded High: Grade 1 (at baseline) to Grade 0 (at post baseline) Number Analyzed 1 participants 1 participants 5 participants 5 participants
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
ALT- CTCAE Graded High: Grade 1 (at baseline) to Grade 1 (at post baseline) Number Analyzed 1 participants 1 participants 5 participants 5 participants
1
 100.0%
1
 100.0%
3
  60.0%
2
  40.0%
ALT- CTCAE Graded High: Grade 1 (at baseline) to Grade 2 (at post baseline) Number Analyzed 1 participants 1 participants 5 participants 5 participants
0
   0.0%
0
   0.0%
1
  20.0%
2
  40.0%
ALT- CTCAE Graded High: Grade 1 (at baseline) to Grade 3 (at post baseline) Number Analyzed 1 participants 1 participants 5 participants 5 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
  20.0%
ALT- CTCAE Graded High: Grade 2 (at baseline) to Grade 2 (at post baseline) Number Analyzed 1 participants 0 participants 1 participants 1 participants
1
 100.0%
1
 100.0%
0
   0.0%
ALT- CTCAE Graded High: Grade 2 (at baseline) to Grade 3 (at post baseline) Number Analyzed 1 participants 0 participants 1 participants 1 participants
0
   0.0%
0
   0.0%
1
 100.0%
ALT- CTCAE Graded High: Grade 3 (at baseline) to Missing (at post baseline) Number Analyzed 0 participants 0 participants 1 participants 0 participants
1
 100.0%
AST- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 8 participants 7 participants 21 participants 22 participants
3
  37.5%
2
  28.6%
8
  38.1%
5
  22.7%
AST- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 8 participants 7 participants 21 participants 22 participants
5
  62.5%
4
  57.1%
11
  52.4%
13
  59.1%
AST- CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) Number Analyzed 8 participants 7 participants 21 participants 22 participants
0
   0.0%
1
  14.3%
2
   9.5%
2
   9.1%
AST- CTCAE Graded High: Grade 0 (at baseline) to Grade 3 (at post baseline) Number Analyzed 8 participants 7 participants 21 participants 22 participants
0
   0.0%
0
   0.0%
0
   0.0%
2
   9.1%
AST- CTCAE Graded High: Grade 1 (at baseline) to Grade 1 (at post baseline) Number Analyzed 2 participants 4 participants 5 participants 5 participants
2
 100.0%
4
 100.0%
3
  60.0%
1
  20.0%
AST- CTCAE Graded High: Grade 1 (at baseline) to Grade 2 (at post baseline) Number Analyzed 2 participants 4 participants 5 participants 5 participants
0
   0.0%
0
   0.0%
1
  20.0%
3
  60.0%
AST- CTCAE Graded High: Grade 1 (at baseline) to Grade 3 (at post baseline) Number Analyzed 2 participants 4 participants 5 participants 5 participants
0
   0.0%
0
   0.0%
1
  20.0%
1
  20.0%
AST- CTCAE Graded High: Grade 2 (at baseline) to Missing (at post baseline) Number Analyzed 0 participants 0 participants 1 participants 0 participants
1
 100.0%
Albumin- CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 10 participants 8 participants 25 participants 26 participants
4
  40.0%
2
  25.0%
8
  32.0%
8
  30.8%
Albumin- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 10 participants 8 participants 25 participants 26 participants
3
  30.0%
2
  25.0%
9
  36.0%
11
  42.3%
Albumin- CTCAE Graded Low: Grade 0 (at baseline) to Grade 2 (at post baseline) Number Analyzed 10 participants 8 participants 25 participants 26 participants
3
  30.0%
4
  50.0%
7
  28.0%
6
  23.1%
Albumin- CTCAE Graded Low: Grade 0 (at baseline) to Grade 3 (at post baseline) Number Analyzed 10 participants 8 participants 25 participants 26 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.8%
Albumin- CTCAE Graded Low: Grade 0 (at baseline) to Missing (at post baseline) Number Analyzed 10 participants 8 participants 25 participants 26 participants
0
   0.0%
0
   0.0%
1
   4.0%
0
   0.0%
Albumin- CTCAE Graded Low: Grade 1 (at baseline) to Grade 1 (at post baseline) Number Analyzed 0 participants 2 participants 2 participants 1 participants
0
   0.0%
0
   0.0%
1
 100.0%
Albumin- CTCAE Graded Low: Grade 1 (at baseline) to Grade 2 (at post baseline) Number Analyzed 0 participants 2 participants 2 participants 1 participants
2
 100.0%
2
 100.0%
0
   0.0%
Albumin- CTCAE Graded Low: Grade 2 (at baseline) to Grade 2 (at post baseline) Number Analyzed 0 participants 1 participants 0 participants 0 participants
1
 100.0%
Alkaline phosphatase- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 5 participants 4 participants 15 participants 12 participants
2
  40.0%
2
  50.0%
7
  46.7%
6
  50.0%
Alkaline phosphatase- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 5 participants 4 participants 15 participants 12 participants
3
  60.0%
1
  25.0%
8
  53.3%
5
  41.7%
Alkaline phosphatase- CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) Number Analyzed 5 participants 4 participants 15 participants 12 participants
0
   0.0%
1
  25.0%
0
   0.0%
1
   8.3%
Alkaline phosphatase- CTCAE Graded High: Grade 1 (at baseline) to Grade 1 (at post baseline) Number Analyzed 4 participants 4 participants 9 participants 11 participants
1
  25.0%
0
   0.0%
5
  55.6%
7
  63.6%
Alkaline phosphatase- CTCAE Graded High: Grade 1 (at baseline) to Grade 2 (at post baseline) Number Analyzed 4 participants 4 participants 9 participants 11 participants
2
  50.0%
4
 100.0%
3
  33.3%
3
  27.3%
Alkaline phosphatase- CTCAE Graded High: Grade 1 (at baseline) to Grade 3 (at post baseline) Number Analyzed 4 participants 4 participants 9 participants 11 participants
1
  25.0%
0
   0.0%
1
  11.1%
1
   9.1%
Alkaline phosphatase- CTCAE Graded High: Grade 2 (at baseline) to Grade 2 (at post baseline) Number Analyzed 1 participants 1 participants 2 participants 2 participants
0
   0.0%
1
 100.0%
0
   0.0%
0
   0.0%
Alkaline phosphatase- CTCAE Graded High: Grade 2 (at baseline) to Grade 3 (at post baseline) Number Analyzed 1 participants 1 participants 2 participants 2 participants
1
 100.0%
0
   0.0%
2
 100.0%
2
 100.0%
Alkaline phosphatase- CTCAE Graded High: Grade 3 (at baseline) to Grade 3 (at post baseline) Number Analyzed 0 participants 2 participants 1 participants 2 participants
2
 100.0%
0
   0.0%
2
 100.0%
Alkaline phosphatase- CTCAE Graded High: Grade 3 (at baseline) to Missing (at post baseline) Number Analyzed 0 participants 2 participants 1 participants 2 participants
0
0
   0.0%
1
 100.0%
0
   0.0%
Amylase- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 9 participants 11 participants 27 participants 26 participants
8
  88.9%
7
  63.6%
18
  66.7%
20
  76.9%
Amylase- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 9 participants 11 participants 27 participants 26 participants
1
  11.1%
2
  18.2%
5
  18.5%
2
   7.7%
Amylase- CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) Number Analyzed 9 participants 11 participants 27 participants 26 participants
0
   0.0%
0
   0.0%
1
   3.7%
2
   7.7%
Amylase- CTCAE Graded High: Grade 0 (at baseline) to Grade 3 (at post baseline) Number Analyzed 9 participants 11 participants 27 participants 26 participants
0
   0.0%
1
   9.1%
2
   7.4%
2
   7.7%
Amylase- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) Number Analyzed 9 participants 11 participants 27 participants 26 participants
0
   0.0%
1
   9.1%
1
   3.7%
0
   0.0%
Amylase- CTCAE Graded High: Grade 1 (at baseline) to Grade 2 (at post baseline) Number Analyzed 1 participants 0 participants 0 participants 0 participants
1
 100.0%
Amylase- CTCAE Graded High: Grade 2 (at baseline) to Grade 4 (at post baseline) Number Analyzed 0 participants 0 participants 0 participants 1 participants
1
 100.0%
Bilirubin- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 10 participants 10 participants 26 participants 27 participants
10
 100.0%
9
  90.0%
25
  96.2%
24
  88.9%
Bilirubin- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 10 participants 10 participants 26 participants 27 participants
0
   0.0%
0
   0.0%
1
   3.8%
2
   7.4%
Bilirubin- CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) Number Analyzed 10 participants 10 participants 26 participants 27 participants
0
   0.0%
1
  10.0%
0
   0.0%
1
   3.7%
Bilirubin- CTCAE Graded High: Grade 1 (at baseline) to Grade 2 (at post baseline) Number Analyzed 0 participants 1 participants 0 participants 0 participants
1
 100.0%
Bilirubin- CTCAE Graded High: Grade 4 (at baseline) to Missing (at post baseline) Number Analyzed 0 participants 0 participants 1 participants 0 participants
1
 100.0%
Corrected Calcium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 26 participants
7
  70.0%
11
 100.0%
24
  88.9%
25
  96.2%
Corrected Calcium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 26 participants
3
  30.0%
0
   0.0%
2
   7.4%
1
   3.8%
Corrected Calcium- CTCAE Graded Low: Grade 0 (at baseline) to Missing (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 26 participants
0
   0.0%
0
   0.0%
1
   3.7%
0
   0.0%
Corrected Calcium- CTCAE Graded Low: Grade 1 (at baseline) to Grade 0 (at post baseline) Number Analyzed 0 participants 0 participants 0 participants 1 participants
1
 100.0%
Corrected Calcium- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 26 participants
10
 100.0%
11
 100.0%
25
  92.6%
25
  96.2%
Corrected Calcium- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 26 participants
0
   0.0%
0
   0.0%
1
   3.7%
1
   3.8%
Corrected Calcium- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 26 participants
0
   0.0%
0
   0.0%
1
   3.7%
0
   0.0%
Corrected Calcium- CTCAE Graded High: Grade 1 (at baseline) to Grade 0 (at post baseline) Number Analyzed 0 participants 0 participants 0 participants 1 participants
1
 100.0%
Creatine kinase- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 9 participants 10 participants 27 participants 23 participants
1
  11.1%
3
  30.0%
3
  11.1%
7
  30.4%
Creatine kinase- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 9 participants 10 participants 27 participants 23 participants
3
  33.3%
4
  40.0%
11
  40.7%
7
  30.4%
Creatine kinase- CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) Number Analyzed 9 participants 10 participants 27 participants 23 participants
4
  44.4%
2
  20.0%
6
  22.2%
8
  34.8%
Creatine kinase- CTCAE Graded High: Grade 0 (at baseline) to Grade 3 (at post baseline) Number Analyzed 9 participants 10 participants 27 participants 23 participants
1
  11.1%
1
  10.0%
5
  18.5%
1
   4.3%
Creatine kinase- CTCAE Graded High: Grade 0 (at baseline) to Grade 4 (at post baseline) Number Analyzed 9 participants 10 participants 27 participants 23 participants
0
   0.0%
0
   0.0%
1
   3.7%
0
   0.0%
Creatine kinase- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) Number Analyzed 9 participants 10 participants 27 participants 23 participants
0
   0.0%
0
   0.0%
1
   3.7%
0
   0.0%
Creatine kinase- CTCAE Graded High: Grade 1 (at baseline) to Grade 2 (at post baseline) Number Analyzed 1 participants 1 participants 0 participants 3 participants
0
   0.0%
1
 100.0%
1
  33.3%
Creatine kinase- CTCAE Graded High: Grade 1 (at baseline) to Grade 3 (at post baseline) Number Analyzed 1 participants 1 participants 0 participants 3 participants
1
 100.0%
0
   0.0%
1
  33.3%
Creatine kinase- CTCAE Graded High: Grade 1 (at baseline) to Grade 4 (at post baseline) Number Analyzed 1 participants 1 participants 0 participants 3 participants
0
   0.0%
0
   0.0%
1
  33.3%
Creatine kinase - CTCAE Graded High: Missing (at baseline) to Grade 1 (at post baseline) Number Analyzed 0 participants 0 participants 0 participants 1 participants
1
 100.0%
Creatinine- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 27 participants
1
  10.0%
2
  18.2%
6
  22.2%
7
  25.9%
Creatinine- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 27 participants
7
  70.0%
7
  63.6%
14
  51.9%
18
  66.7%
Creatinine- CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 27 participants
2
  20.0%
2
  18.2%
5
  18.5%
2
   7.4%
Creatinine- CTCAE Graded High: Grade 0 (at baseline) to Grade 4 (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 27 participants
0
   0.0%
0
   0.0%
1
   3.7%
0
   0.0%
Creatinine- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 27 participants
0
   0.0%
0
   0.0%
1
   3.7%
0
   0.0%
Glucose- CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 10 participants 11 participants 26 participants 26 participants
10
 100.0%
10
  90.9%
23
  88.5%
26
 100.0%
Glucose- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 10 participants 11 participants 26 participants 26 participants
0
   0.0%
1
   9.1%
1
   3.8%
0
   0.0%
Glucose- CTCAE Graded Low: Grade 0 (at baseline) to Grade 2 (at post baseline) Number Analyzed 10 participants 11 participants 26 participants 26 participants
0
   0.0%
0
   0.0%
1
   3.8%
0
   0.0%
Glucose- CTCAE Graded Low: Grade 0 (at baseline) to Missing (at post baseline) Number Analyzed 10 participants 11 participants 26 participants 26 participants
0
   0.0%
0
   0.0%
1
   3.8%
0
   0.0%
Glucose- CTCAE Graded Low: Grade 1 (at baseline) to Grade 0 (at post baseline) Number Analyzed 0 participants 0 participants 1 participants 1 participants
0
   0.0%
1
 100.0%
Glucose- CTCAE Graded Low: Grade 1 (at baseline) to Grade 1 (at post baseline) Number Analyzed 0 participants 0 participants 1 participants 1 participants
1
 100.0%
0
   0.0%
Glucose- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 9 participants 10 participants 24 participants 21 participants
7
  77.8%
6
  60.0%
18
  75.0%
14
  66.7%
Glucose- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 9 participants 10 participants 24 participants 21 participants
0
   0.0%
1
  10.0%
1
   4.2%
1
   4.8%
Glucose - CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) Number Analyzed 9 participants 10 participants 24 participants 21 participants
1
  11.1%
1
  10.0%
0
   0.0%
1
   4.8%
Glucose- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) Number Analyzed 9 participants 10 participants 24 participants 21 participants
1
  11.1%
2
  20.0%
5
  20.8%
5
  23.8%
Glucose- CTCAE Graded High: Grade 1 (at baseline) to Grade 0 (at post baseline) Number Analyzed 0 participants 0 participants 1 participants 1 participants
1
 100.0%
0
   0.0%
Glucose - CTCAE Graded High: Grade 1 (at baseline) to Grade 2 (at post baseline) Number Analyzed 0 participants 0 participants 1 participants 1 participants
0
   0.0%
1
 100.0%
Glucose- CTCAE Graded High: Grade 3 (at baseline) to Grade 2 (at post baseline) Number Analyzed 0 participants 0 participants 1 participants 2 participants
1
 100.0%
0
   0.0%
Glucose- CTCAE Graded High: Grade 3 (at baseline) to Grade 3 (at post baseline) Number Analyzed 0 participants 0 participants 1 participants 2 participants
0
   0.0%
1
  50.0%
Glucose- CTCAE Graded High: Grade 3 (at baseline) to Missing (at post baseline) Number Analyzed 0 participants 0 participants 1 participants 2 participants
0
   0.0%
1
  50.0%
Glucose- CTCAE Graded High: Missing (at baseline) to Grade 0 (at post baseline) Number Analyzed 1 participants 1 participants 1 participants 3 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
Glucose- CTCAE Graded High: Missing (at baseline) to Grade 3 (at post baseline) Number Analyzed 1 participants 1 participants 1 participants 3 participants
0
   0.0%
0
   0.0%
1
 100.0%
0
   0.0%
Glucose- CTCAE Graded High: Missing (at baseline) to Missing (at post baseline) Number Analyzed 1 participants 1 participants 1 participants 3 participants
1
 100.0%
1
 100.0%
0
   0.0%
2
  66.7%
Lipase- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 9 participants 10 participants 25 participants 23 participants
5
  55.6%
6
  60.0%
17
  68.0%
15
  65.2%
Lipase- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 9 participants 10 participants 25 participants 23 participants
2
  22.2%
2
  20.0%
2
   8.0%
4
  17.4%
Lipase- CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) Number Analyzed 9 participants 10 participants 25 participants 23 participants
1
  11.1%
1
  10.0%
1
   4.0%
0
   0.0%
Lipase- CTCAE Graded High: Grade 0 (at baseline) to Grade 3 (at post baseline) Number Analyzed 9 participants 10 participants 25 participants 23 participants
1
  11.1%
0
   0.0%
4
  16.0%
3
  13.0%
Lipase- CTCAE Graded High: Grade 0 (at baseline) to Grade 4 (at post baseline) Number Analyzed 9 participants 10 participants 25 participants 23 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.3%
Lipase- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) Number Analyzed 9 participants 10 participants 25 participants 23 participants
0
   0.0%
1
  10.0%
1
   4.0%
0
   0.0%
Lipase- CTCAE Graded High: Grade 1 (at baseline) to Grade 0 (at post baseline) Number Analyzed 1 participants 1 participants 2 participants 3 participants
1
 100.0%
0
   0.0%
1
  50.0%
0
   0.0%
Lipase- CTCAE Graded High: Grade 1 (at baseline) to Grade 1 (at post baseline) Number Analyzed 1 participants 1 participants 2 participants 3 participants
0
   0.0%
1
 100.0%
1
  50.0%
2
  66.7%
Lipase- CTCAE Graded High: Grade 1 (at baseline) to Grade 3 (at post baseline) Number Analyzed 1 participants 1 participants 2 participants 3 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
Lipase- CTCAE Graded High: Grade 4 (at baseline) to Grade 4 (at post baseline) Number Analyzed 0 participants 0 participants 0 participants 1 participants
1
 100.0%
Magnesium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 9 participants 11 participants 26 participants 27 participants
8
  88.9%
10
  90.9%
22
  84.6%
24
  88.9%
Magnesium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 9 participants 11 participants 26 participants 27 participants
1
  11.1%
1
   9.1%
3
  11.5%
2
   7.4%
Magnesium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 2 (at post baseline) Number Analyzed 9 participants 11 participants 26 participants 27 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.7%
Magnesium- CTCAE Graded Low: Grade 0 (at baseline) to Missing (at post baseline) Number Analyzed 9 participants 11 participants 26 participants 27 participants
0
   0.0%
0
   0.0%
1
   3.8%
0
   0.0%
Magnesium- CTCAE Graded Low: Grade 1 (at baseline) to Grade 2 (at post baseline) Number Analyzed 1 participants 0 participants 0 participants 0 participants
1
 100.0%
Magnesium- CTCAE Graded Low: Grade 2 (at baseline) to Grade 3 (at post baseline) Number Analyzed 0 participants 0 participants 1 participants 0 participants
1
 100.0%
Magnesium- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 27 participants
10
 100.0%
11
 100.0%
26
  96.3%
27
 100.0%
Magnesium- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 27 participants
0
   0.0%
0
   0.0%
1
   3.7%
0
   0.0%
Potassium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 10 participants 11 participants 26 participants 27 participants
7
  70.0%
9
  81.8%
20
  76.9%
23
  85.2%
Potassium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 10 participants 11 participants 26 participants 27 participants
3
  30.0%
2
  18.2%
3
  11.5%
4
  14.8%
Potassium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 3 (at post baseline) Number Analyzed 10 participants 11 participants 26 participants 27 participants
0
   0.0%
0
   0.0%
1
   3.8%
0
   0.0%
Potassium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 4 (at post baseline) Number Analyzed 10 participants 11 participants 26 participants 27 participants
0
   0.0%
0
   0.0%
1
   3.8%
0
   0.0%
Potassium- CTCAE Graded Low: Grade 0 (at baseline) to Missing (at post baseline) Number Analyzed 10 participants 11 participants 26 participants 27 participants
0
   0.0%
0
   0.0%
1
   3.8%
0
   0.0%
Potassium- CTCAE Graded Low: Grade 3 (at baseline) to Grade 3 (at post baseline) Number Analyzed 0 participants 0 participants 1 participants 0 participants
1
 100.0%
Potassium- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 10 participants 11 participants 26 participants 27 participants
9
  90.0%
10
  90.9%
23
  88.5%
23
  85.2%
Potassium- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 10 participants 11 participants 26 participants 27 participants
1
  10.0%
1
   9.1%
2
   7.7%
4
  14.8%
Potassium- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) Number Analyzed 10 participants 11 participants 26 participants 27 participants
0
   0.0%
0
   0.0%
1
   3.8%
0
   0.0%
Potassium- CTCAE Graded High: Grade 1 (at baseline) to Grade 0 (at post baseline) Number Analyzed 0 participants 0 participants 1 participants 0 participants
1
 100.0%
Sodium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 10 participants 10 participants 25 participants 27 participants
9
  90.0%
7
  70.0%
19
  76.0%
23
  85.2%
Sodium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 10 participants 10 participants 25 participants 27 participants
1
  10.0%
3
  30.0%
3
  12.0%
1
   3.7%
Sodium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 3 (at post baseline) Number Analyzed 10 participants 10 participants 25 participants 27 participants
0
   0.0%
0
   0.0%
1
   4.0%
2
   7.4%
Sodium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 4 (at post baseline) Number Analyzed 10 participants 10 participants 25 participants 27 participants
0
   0.0%
0
   0.0%
2
   8.0%
1
   3.7%
Sodium- CTCAE Graded Low: Grade 1 (at baseline) to Grade 1 (at post baseline) Number Analyzed 0 participants 0 participants 2 participants 0 participants
1
  50.0%
Sodium- CTCAE Graded Low: Grade 1 (at baseline) to Missing (at post baseline) Number Analyzed 0 participants 0 participants 2 participants 0 participants
1
  50.0%
Sodium- CTCAE Graded Low: Grade 3 (at baseline) to Grade 3 (at post baseline) Number Analyzed 0 participants 1 participants 0 participants 0 participants
1
 100.0%
Sodium- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 27 participants
10
 100.0%
11
 100.0%
23
  85.2%
22
  81.5%
Sodium- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 27 participants
0
   0.0%
0
   0.0%
3
  11.1%
5
  18.5%
Sodium- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) Number Analyzed 10 participants 11 participants 27 participants 27 participants
0
   0.0%
0
   0.0%
1
   3.7%
0
   0.0%
10.Secondary Outcome
Title Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on Normal Range: Chemistry and Thyroid Function
Hide Description Chemistry laboratory parameters: Blood urea nitrogen (BUN), Total protein, Chloride, Cancer antigen 19-9 (CA 19-9), Brain natriuretic peptide (BNP), Bicarbonate, Direct bilirubin, Carcinoembryonic antigen (CEA), Lactate dehydrogenase (LDH), Uric acid, Troponin I. Thyroid panel laboratory parameters: Thyroid-stimulating hormone (TSH), Free triiodothyronine (T3), Free thyroxine (T4). Laboratory values were as per laboratory normal ranges. Values above range were reported as high and values below range as low. Shift in chemistry and thyroid panel severity from baseline grade low, normal, high and missing to the post baseline grades as low, normal, high and missing are reported in this outcome measure. Categories with at least 1 non-zero data values are reported.
Time Frame Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set included of all participants who received at least 1 dose of study drug. Here "Number Analyzed" signifies number of participants evaluable for specified rows.
Arm/Group Title Phase 1b: Nivolumab+Binimetinib Phase 1b: Nivolumab+Ipilimumab+Binimetinib Phase 2: Nivolumab+Binimetinib Phase 2: Nivolumab+Ipilimumab+Binimetinib
Hide Arm/Group Description:
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
Overall Number of Participants Analyzed 10 11 27 27
Measure Type: Count of Participants
Unit of Measure: Participants
BNP: Normal (at baseline) to Normal (at post baseline) Number Analyzed 9 participants 9 participants 27 participants 25 participants
8
  88.9%
6
  66.7%
24
  88.9%
22
  88.0%
BNP: Normal (at baseline) to High (at post baseline) Number Analyzed 9 participants 9 participants 27 participants 25 participants
1
  11.1%
3
  33.3%
2
   7.4%
3
  12.0%
BNP: Normal (at baseline) to Missing (at post baseline) Number Analyzed 9 participants 9 participants 27 participants 25 participants
0
   0.0%
0
   0.0%
1
   3.7%
0
   0.0%
BNP: High (at baseline) to Normal (at post baseline) Number Analyzed 1 participants 2 participants 0 participants 2 participants
0
   0.0%
2
 100.0%
0
   0.0%
BNP: High (at baseline) to High (at post baseline) Number Analyzed 1 participants 2 participants 0 participants 2 participants
1
 100.0%
0
   0.0%
2
 100.0%
BUN: Normal (at baseline) to Normal (at post baseline) Number Analyzed 7 participants 9 participants 25 participants 21 participants
4
  57.1%
3
  33.3%
15
  60.0%
14
  66.7%
BUN (mmol/L): Normal (at baseline) to High (at post baseline) Number Analyzed 7 participants 9 participants 25 participants 21 participants
3
  42.9%
5
  55.6%
9
  36.0%
7
  33.3%
BUN: Normal (at baseline) to Missing (at post baseline) Number Analyzed 7 participants 9 participants 25 participants 21 participants
0
   0.0%
1
  11.1%
1
   4.0%
0
   0.0%
BUN: High (at baseline) to Normal (at post baseline) Number Analyzed 3 participants 2 participants 2 participants 6 participants
0
   0.0%
0
   0.0%
2
 100.0%
3
  50.0%
BUN: High (at baseline) to High (at post baseline) Number Analyzed 3 participants 2 participants 2 participants 6 participants
3
 100.0%
2
 100.0%
0
   0.0%
3
  50.0%
Bicarbonate: Low (at baseline) to Normal (at post baseline) Number Analyzed 0 participants 2 participants 1 participants 3 participants
1
  50.0%
0
   0.0%
3
 100.0%
Bicarbonate: Low (at baseline) to High (at post baseline) Number Analyzed 0 participants 2 participants 1 participants 3 participants
1
  50.0%
1
 100.0%
0
   0.0%
Bicarbonate: Normal (at baseline) to Low (at post baseline) Number Analyzed 10 participants 9 participants 26 participants 24 participants
2
  20.0%
1
  11.1%
6
  23.1%
9
  37.5%
Bicarbonate: Normal (at baseline) to Normal (at post baseline) Number Analyzed 10 participants 9 participants 26 participants 24 participants
7
  70.0%
6
  66.7%
18
  69.2%
11
  45.8%
Bicarbonate: Normal (at baseline) to High (at post baseline) Number Analyzed 10 participants 9 participants 26 participants 24 participants
1
  10.0%
2
  22.2%
1
   3.8%
3
  12.5%
Bicarbonate: Normal (at baseline) to High and Low (at post baseline) Number Analyzed 10 participants 9 participants 26 participants 24 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.2%
Bicarbonate: Normal (at baseline) to Missing (at post baseline) Number Analyzed 10 participants 9 participants 26 participants 24 participants
0
   0.0%
0
   0.0%
1
   3.8%
0
   0.0%
CA 19-9: Normal (at baseline) to Normal (at post baseline) Number Analyzed 3 participants 4 participants 8 participants 9 participants
3
 100.0%
3
  75.0%
6
  75.0%
7
  77.8%
CA 19-9: Normal (at baseline) to High (at post baseline) Number Analyzed 3 participants 4 participants 8 participants 9 participants
0
   0.0%
0
   0.0%
2
  25.0%
1
  11.1%
CA 19-9: Normal (at baseline) to Missing (at post baseline) Number Analyzed 3 participants 4 participants 8 participants 9 participants
0
   0.0%
1
  25.0%
0
   0.0%
1
  11.1%
CA 19-9: High (at baseline) to Normal (at post baseline) Number Analyzed 7 participants 7 participants 19 participants 18 participants
0
   0.0%
0
   0.0%
1
   5.3%
1
   5.6%
CA 19-9: High (at baseline) to High (at post baseline) Number Analyzed 7 participants 7 participants 19 participants 18 participants
7
 100.0%
6
  85.7%
16
  84.2%
16
  88.9%
CA 19-9: High (at baseline) to Missing (at post baseline) Number Analyzed 7 participants 7 participants 19 participants 18 participants
0
   0.0%
1
  14.3%
2
  10.5%
1
   5.6%
CEA: Normal (at baseline) to Normal (at post baseline) Number Analyzed 1 participants 0 participants 3 participants 6 participants
1
 100.0%
1
  33.3%
3
  50.0%
CEA: Normal (at baseline) to High (at post baseline) Number Analyzed 1 participants 0 participants 3 participants 6 participants
0
   0.0%
2
  66.7%
2
  33.3%
CEA: Normal (at baseline) to Missing (at post baseline) Number Analyzed 1 participants 0 participants 3 participants 6 participants
0
   0.0%
0
   0.0%
1
  16.7%
CEA: High (at baseline) to Normal (at post baseline) Number Analyzed 9 participants 11 participants 24 participants 21 participants
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
CEA: High (at baseline) to High (at post baseline) Number Analyzed 9 participants 11 participants 24 participants 21 participants
9
 100.0%
9
  81.8%
20
  83.3%
20
  95.2%
CEA: High (at baseline) to Missing (at post baseline) Number Analyzed 9 participants 11 participants 24 participants 21 participants
0
   0.0%
2
  18.2%
3
  12.5%
1
   4.8%
Chloride: Low (at baseline) to Low (at post baseline) Number Analyzed 0 participants 1 participants 2 participants 1 participants
1
 100.0%
1
  50.0%
1
 100.0%
Chloride: Low (at baseline) to Missing (at post baseline) Number Analyzed 0 participants 1 participants 2 participants 1 participants
0
   0.0%
1
  50.0%
0
   0.0%
Chloride: Normal (at baseline) to Low (at post baseline) Number Analyzed 10 participants 10 participants 25 participants 26 participants
2
  20.0%
2
  20.0%
8
  32.0%
3
  11.5%
Chloride: Normal (at baseline) to Normal (at post baseline) Number Analyzed 10 participants 10 participants 25 participants 26 participants
8
  80.0%
7
  70.0%
15
  60.0%
22
  84.6%
Chloride: Normal (at baseline) to High (at post baseline) Number Analyzed 10 participants 10 participants 25 participants 26 participants
0
   0.0%
0
   0.0%
2
   8.0%
1
   3.8%
Chloride: Normal (at baseline) to High & Low (at post baseline) Number Analyzed 10 participants 10 participants 25 participants 26 participants
0
   0.0%
1
  10.0%
0
   0.0%
0
   0.0%
Free T3: Low (at baseline) to Low (at post baseline) Number Analyzed 0 participants 0 participants 1 participants 2 participants
0
   0.0%
1
  50.0%
Free T3: Low (at baseline) to Missing (at post baseline) Number Analyzed 0 participants 0 participants 1 participants 2 participants
1
 100.0%
1
  50.0%
Free T3: Normal (at baseline) to Low (at post baseline) Number Analyzed 10 participants 11 participants 26 participants 23 participants
3
  30.0%
5
  45.5%
8
  30.8%
7
  30.4%
Free T3: Normal (at baseline) to Normal (at post baseline) Number Analyzed 10 participants 11 participants 26 participants 23 participants
7
  70.0%
5
  45.5%
15
  57.7%
15
  65.2%
Free T3: Normal (at baseline) to High and Low (at post baseline) Number Analyzed 10 participants 11 participants 26 participants 23 participants
0
   0.0%
0
   0.0%
1
   3.8%
0
   0.0%
Free T3: Normal (at baseline) to Missing (at post baseline) Number Analyzed 10 participants 11 participants 26 participants 23 participants
0
   0.0%
1
   9.1%
2
   7.7%
1
   4.3%
Free T3: High (at baseline) to High (at post baseline) Number Analyzed 0 participants 0 participants 0 participants 2 participants
2
 100.0%
Free T4: Low (at baseline) to Low (at post baseline) Number Analyzed 0 participants 1 participants 0 participants 1 participants
0
   0.0%
1
 100.0%
Free T4: Low (at baseline) to Normal (at post baseline) Number Analyzed 0 participants 1 participants 0 participants 1 participants
1
 100.0%
0
   0.0%
Free T4: Normal (at baseline) to Low (at post baseline) Number Analyzed 10 participants 10 participants 26 participants 24 participants
0
   0.0%
1
  10.0%
2
   7.7%
3
  12.5%
Free T4: Normal (at baseline) to Normal (at post baseline) Number Analyzed 10 participants 10 participants 26 participants 24 participants
10
 100.0%
8
  80.0%
17
  65.4%
17
  70.8%
Free T4: Normal (at baseline) to High (at post baseline) Number Analyzed 10 participants 10 participants 26 participants 24 participants
0
   0.0%
0
   0.0%
3
  11.5%
1
   4.2%
Free T4: Normal (at baseline) to High and Low (at post baseline) Number Analyzed 10 participants 10 participants 26 participants 24 participants
0
   0.0%
0
   0.0%
1
   3.8%
1
   4.2%
Free T4: Normal (at baseline) to Missing (at post baseline) Number Analyzed 10 participants 10 participants 26 participants 24 participants
0
   0.0%
1
  10.0%
3
  11.5%
2
   8.3%
Free T4: High (at baseline) to Low (at post baseline) Number Analyzed 0 participants 0 participants 1 participants 2 participants
0
   0.0%
1
  50.0%
Free T4: High (at baseline) to Normal (at post baseline) Number Analyzed 0 participants 0 participants 1 participants 2 participants
1
 100.0%
1
  50.0%
LDH: Low (at baseline) to Low (at post baseline) Number Analyzed 1 participants 0 participants 0 participants 0 participants
1
 100.0%
LDH: Normal (at baseline) to Normal (at post baseline) Number Analyzed 6 participants 5 participants 20 participants 15 participants
1
  16.7%
1
  20.0%
6
  30.0%
5
  33.3%
LDH: Normal (at baseline) to High (at post baseline) Number Analyzed 6 participants 5 participants 20 participants 15 participants
5
  83.3%
4
  80.0%
14
  70.0%
10
  66.7%
LDH: High (at baseline) to Normal (at post baseline) Number Analyzed 3 participants 6 participants 7 participants 12 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
   8.3%
LDH: High (at baseline) to High (at post baseline) Number Analyzed 3 participants 6 participants 7 participants 12 participants
3
 100.0%
6
 100.0%
6
  85.7%
11
  91.7%
LDH: High (at baseline) to Missing (at post baseline) Number Analyzed 3 participants 6 participants 7 participants 12 participants
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
Protein: Low (at baseline) to Low (at post baseline) Number Analyzed 0 participants 1 participants 0 participants 0 participants
1
 100.0%
Protein: Normal (at baseline) to Low (at post baseline) Number Analyzed 10 participants 10 participants 27 participants 27 participants
5
  50.0%
6
  60.0%
11
  40.7%
11
  40.7%
Protein: Normal (at baseline) to Normal (at post baseline) Number Analyzed 10 participants 10 participants 27 participants 27 participants
5
  50.0%
4
  40.0%
12
  44.4%
14
  51.9%
Protein: Normal (at baseline) to High (at post baseline) Number Analyzed 10 participants 10 participants 27 participants 27 participants
0
   0.0%
0
   0.0%
0
   0.0%
2
   7.4%
Protein: Normal (at baseline) to High and Low (at post baseline) Number Analyzed 10 participants 10 participants 27 participants 27 participants
0
   0.0%
0
   0.0%
3
  11.1%
0
   0.0%
Protein: Normal (at baseline) to Missing (at post baseline) Number Analyzed 10 participants 10 participants 27 participants 27 participants
0
   0.0%
0
   0.0%
1
   3.7%
0
   0.0%
TSH: Low (at baseline) to Low (at post baseline) Number Analyzed 0 participants 0 participants 0 participants 1 participants
1
 100.0%
TSH: Normal (at baseline) to Low (at post baseline) Number Analyzed 9 participants 7 participants 24 participants 26 participants
0
   0.0%
0
   0.0%
2
   8.3%
3
  11.5%
TSH: Normal (at baseline) to Normal (at post baseline) Number Analyzed 9 participants 7 participants 24 participants 26 participants
8
  88.9%
7
 100.0%
14
  58.3%
20
  76.9%
TSH: Normal (at baseline) to High (at post baseline) Number Analyzed 9 participants 7 participants 24 participants 26 participants
1
  11.1%
0
   0.0%
3
  12.5%
1
   3.8%
TSH: Normal (at baseline) to High and Low (at post baseline) Number Analyzed 9 participants 7 participants 24 participants 26 participants
0
   0.0%
0
   0.0%
2
   8.3%
0
   0.0%
TSH: Normal (at baseline) to Missing (at post baseline) Number Analyzed 9 participants 7 participants 24 participants 26 participants
0
   0.0%
0
   0.0%
3
  12.5%
2
   7.7%
TSH: High (at baseline) to Normal (at post baseline) Number Analyzed 1 participants 4 participants 3 participants 0 participants
0
   0.0%
2
  50.0%
2
  66.7%
TSH: High (at baseline) to High (at post baseline) Number Analyzed 1 participants 4 participants 3 participants 0 participants
1
 100.0%
1
  25.0%
1
  33.3%
TSH: High (at baseline) to Missing (at post baseline) Number Analyzed 1 participants 4 participants 3 participants 0 participants
0
   0.0%
1
  25.0%
0
   0.0%
Troponin I: Normal (at baseline) to Normal (at post baseline) Number Analyzed 0 participants 2 participants 26 participants 26 participants
2
 100.0%
11
  42.3%
10
  38.5%
Troponin I: Normal (at baseline) to High (at post baseline) Number Analyzed 0 participants 2 participants 26 participants 26 participants
0
   0.0%
1
   3.8%
2
   7.7%
Troponin I: Normal (at baseline) to Missing (at post baseline) Number Analyzed 0 participants 2 participants 26 participants 26 participants
0
   0.0%
14
  53.8%
14
  53.8%
Troponin I: Missing (at baseline) to Normal (at post baseline) Number Analyzed 5 participants 3 participants 0 participants 1 participants
4
  80.0%
3
 100.0%
1
 100.0%
Troponin I: Missing (at baseline) to High (at post baseline) Number Analyzed 5 participants 3 participants 0 participants 1 participants
1
  20.0%
0
   0.0%
0
   0.0%
Uric acid: Low (at baseline) to Low (at post baseline) Number Analyzed 0 participants 1 participants 1 participants 3 participants
0
   0.0%
0
   0.0%
2
  66.7%
Uric acid: Low (at baseline) to Normal (at post baseline) Number Analyzed 0 participants 1 participants 1 participants 3 participants
1
 100.0%
0
   0.0%
1
  33.3%
Uric acid: Low (at baseline) to Missing (at post baseline) Number Analyzed 0 participants 1 participants 1 participants 3 participants
0
   0.0%
1
 100.0%
0
   0.0%
Uric acid: Normal (at baseline) to Low (at post baseline) Number Analyzed 9 participants 9 participants 23 participants 21 participants
1
  11.1%
2
  22.2%
4
  17.4%
4
  19.0%
Uric acid: Normal (at baseline) to Normal (at post baseline) Number Analyzed 9 participants 9 participants 23 participants 21 participants
8
  88.9%
5
  55.6%
15
  65.2%
16
  76.2%
Uric acid: Normal (at baseline) to High (at post baseline) Number Analyzed 9 participants 9 participants 23 participants 21 participants
0
   0.0%
2
  22.2%
4
  17.4%
1
   4.8%
Uric acid: High (at baseline) to Normal (at post baseline) Number Analyzed 1 participants 1 participants 3 participants 3 participants
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
Uric acid: High (at baseline) to High (at post baseline) Number Analyzed 1 participants 1 participants 3 participants 3 participants
1
 100.0%
1
 100.0%
2
  66.7%
3
 100.0%
11.Secondary Outcome
Title Number of Participants With Abnormal Hepatic Laboratory Values
Hide Description Criteria for abnormal hepatic laboratory parameters: Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT): >3* upper limit of normal (ULN), >5*ULN, >8*ULN, >10*ULN, >20*ULN; Total bilirubin (TBL) >1.5*ULN, >2*ULN; Alkaline phosphatase (ALP) >2*ULN, >3*ULN. Categories with at least 1 non-zero data values are reported.
Time Frame Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set included of all participants who received at least 1 dose of study drug. Here "Number Analyzed" signifies number of participants evaluable for specified rows.
Arm/Group Title Phase 1b: Nivolumab+Binimetinib Phase 1b: Nivolumab+Ipilimumab+Binimetinib Phase 2: Nivolumab+Binimetinib Phase 2: Nivolumab+Ipilimumab+Binimetinib
Hide Arm/Group Description:
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
Overall Number of Participants Analyzed 10 11 27 27
Measure Type: Count of Participants
Unit of Measure: Participants
ALT: >3 ULN Number Analyzed 9 participants 11 participants 25 participants 26 participants
0
   0.0%
0
   0.0%
2
   8.0%
7
  26.9%
ALT: >5 ULN Number Analyzed 10 participants 11 participants 26 participants 27 participants
0
   0.0%
0
   0.0%
0
   0.0%
5
  18.5%
ALT: >8 ULN Number Analyzed 10 participants 11 participants 26 participants 27 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.7%
AST: >3 ULN Number Analyzed 10 participants 11 participants 26 participants 27 participants
0
   0.0%
1
   9.1%
4
  15.4%
8
  29.6%
AST: >5 ULN Number Analyzed 10 participants 11 participants 26 participants 27 participants
0
   0.0%
0
   0.0%
1
   3.8%
3
  11.1%
AST: >8 ULN Number Analyzed 10 participants 11 participants 26 participants 27 participants
0
   0.0%
0
   0.0%
1
   3.8%
1
   3.7%
ALT or AST: >3 ULN Number Analyzed 9 participants 11 participants 25 participants 26 participants
0
   0.0%
1
   9.1%
3
  12.0%
7
  26.9%
ALT or AST: >5 ULN Number Analyzed 10 participants 11 participants 26 participants 27 participants
0
   0.0%
0
   0.0%
1
   3.8%
4
  14.8%
ALT or AST: >8 ULN Number Analyzed 10 participants 11 participants 26 participants 27 participants
0
   0.0%
0
   0.0%
1
   3.8%
1
   3.7%
Total bilirubin: >1.5 ULN Number Analyzed 9 participants 11 participants 26 participants 26 participants
0
   0.0%
2
  18.2%
0
   0.0%
1
   3.8%
Alkaline phosphatase: >2 ULN Number Analyzed 8 participants 6 participants 22 participants 22 participants
3
  37.5%
3
  50.0%
4
  18.2%
8
  36.4%
Alkaline phosphatase: >3 ULN Number Analyzed 10 participants 8 participants 24 participants 24 participants
4
  40.0%
4
  50.0%
2
   8.3%
4
  16.7%
12.Secondary Outcome
Title Concentration Versus Time Summary of Plasma Concentration of Binimetinib
Hide Description [Not Specified]
Time Frame 1.5 hours post dose of binimetinib on Day 1, 15 of Cycle 1; pre dose of binimetinib on Day 15 of Cycle 1, 2, 3, 4, 5
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic analysis set included of all participants who received at least 1 dose of binimetinib and have at least one evaluable bioanalytical result. Here "Number Analyzed" signifies number of participants evaluable for specified rows.
Arm/Group Title Phase 1b: Nivolumab+Binimetinib Phase 1b: Nivolumab+Ipilimumab+Binimetinib Phase 2: Nivolumab+Binimetinib Phase 2: Nivolumab+Ipilimumab+Binimetinib
Hide Arm/Group Description:
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
Overall Number of Participants Analyzed 10 11 26 27
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram per milliliter
Cycle 1 Day 1: 1.5 Hours post dose Number Analyzed 10 participants 11 participants 21 participants 23 participants
228
(152.2%)
163
(129.6%)
261
(90.9%)
217
(134.5%)
Cycle 1 Day 15: pre dose Number Analyzed 4 participants 5 participants 12 participants 8 participants
135
(60.9%)
125
(103.9%)
77.0
(141.2%)
81.8
(143.6%)
Cycle 1 Day 15: 1.5 Hours post dose Number Analyzed 4 participants 8 participants 15 participants 18 participants
542
(57.6%)
414
(24.5%)
294
(84.4%)
324
(83.3%)
Cycle 2 Day 15: pre dose Number Analyzed 4 participants 2 participants 7 participants 7 participants
108
(52.9%)
NA [1] 
(NA%)
88.5
(111.3%)
120
(77.7%)
Cycle 3 Day 15: pre dose Number Analyzed 3 participants 2 participants 1 participants 3 participants
140
(42.0%)
NA [2] 
(NA%)
NA [2] 
(NA%)
89.2
(183.4%)
Cycle 4 Day 15: pre dose Number Analyzed 2 participants 1 participants 1 participants 1 participants
NA [2] 
(NA%)
NA [2] 
(NA%)
NA [2] 
(NA%)
NA [2] 
(NA%)
Cycle 5 Day 15: pre dose Number Analyzed 1 participants 0 participants 1 participants 1 participants
NA [2] 
(NA%)
NA [2] 
(NA%)
NA [2] 
(NA%)
[1]
Geometric mean and geometric coefficient of variation were not estimable as concentration was below the limit of quantification (LOQ).
[2]
Geometric mean and geometric coefficient of variation were not estimable as concentration was below LOQ.
Time Frame All-Cause Mortality: From start of the treatment up to 150 days after last dose (Phase 1b: maximum up to 13 months approximately and Phase 2: maximum up to 30 months approximately); TEAEs (including serious and other AEs): From start of the treatment up to 30 days after last dose (Phase 1b: maximum up to 9 months approximately and Phase 2: maximum up to 26 months approximately)
Adverse Event Reporting Description Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety set was evaluated. Both TEAE and treatment related AEs were monitored.
 
Arm/Group Title Phase 1b: Nivolumab+Binimetinib Phase 1b: Nivolumab+Ipilimumab+Binimetinib Phase 2: Nivolumab+Binimetinib Phase 2: Nivolumab+Ipilimumab+Binimetinib
Hide Arm/Group Description Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days.
All-Cause Mortality
Phase 1b: Nivolumab+Binimetinib Phase 1b: Nivolumab+Ipilimumab+Binimetinib Phase 2: Nivolumab+Binimetinib Phase 2: Nivolumab+Ipilimumab+Binimetinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/10 (80.00%)   8/11 (72.73%)   20/27 (74.07%)   21/27 (77.78%) 
Hide Serious Adverse Events
Phase 1b: Nivolumab+Binimetinib Phase 1b: Nivolumab+Ipilimumab+Binimetinib Phase 2: Nivolumab+Binimetinib Phase 2: Nivolumab+Ipilimumab+Binimetinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/10 (50.00%)   6/11 (54.55%)   12/27 (44.44%)   11/27 (40.74%) 
Cardiac disorders         
Myocarditis * 1  0/10 (0.00%)  1/11 (9.09%)  1/27 (3.70%)  0/27 (0.00%) 
Pericardial effusion * 1  0/10 (0.00%)  0/11 (0.00%)  2/27 (7.41%)  0/27 (0.00%) 
Acute coronary syndrome * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Cardiac failure * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
Endocrine disorders         
Hypophysitis * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  1/27 (3.70%) 
Gastrointestinal disorders         
Intestinal obstruction * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  1/27 (3.70%) 
Abdominal pain * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  1/27 (3.70%) 
Colitis * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Constipation * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
Diarrhoea * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
Ileus * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  1/27 (3.70%) 
Nausea * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
Pancreatitis * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  1/27 (3.70%) 
Small intestinal obstruction * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Vomiting * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
General disorders         
Pyrexia * 1  1/10 (10.00%)  0/11 (0.00%)  1/27 (3.70%)  1/27 (3.70%) 
Asthenia * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
Localised oedema * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  1/27 (3.70%) 
Pain * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
Hepatobiliary disorders         
Hepatitis * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  1/27 (3.70%) 
Infections and infestations         
Pneumonia * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  2/27 (7.41%) 
Abdominal infection * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  1/27 (3.70%) 
Bacterial sepsis * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Candida infection * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  1/27 (3.70%) 
Cellulitis * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  1/27 (3.70%) 
Empyema * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  1/27 (3.70%) 
Infected seroma * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
Klebsiella bacteraemia * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
Lung infection * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
Periorbital cellulitis * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  1/27 (3.70%) 
Pneumocystis jirovecii pneumonia * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Pneumonia bacterial * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Injury, poisoning and procedural complications         
Fall * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  1/27 (3.70%) 
Hip fracture * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Infusion related reaction * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
Investigations         
Aspartate aminotransferase increased * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
Blood creatine phosphokinase increased * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
Transaminases increased * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  1/27 (3.70%) 
Metabolism and nutrition disorders         
Decreased appetite * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
Hyponatraemia * 1  0/10 (0.00%)  1/11 (9.09%)  1/27 (3.70%)  0/27 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back pain * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  1/27 (3.70%) 
Myositis * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
Pain in extremity * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Tumour associated fever * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Nervous system disorders         
Ataxia * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
Renal and urinary disorders         
Nephritis * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
Renal colic * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Pleural effusion * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  2/27 (7.41%) 
Pneumonitis * 1  0/10 (0.00%)  2/11 (18.18%)  0/27 (0.00%)  0/27 (0.00%) 
Hypoxia * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Pleurisy * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Pulmonary oedema * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
Skin and subcutaneous tissue disorders         
Dermatitis acneiform * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Skin reaction * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Vascular disorders         
Superior vena cava syndrome * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
1
Term from vocabulary, MedDRA v21.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase 1b: Nivolumab+Binimetinib Phase 1b: Nivolumab+Ipilimumab+Binimetinib Phase 2: Nivolumab+Binimetinib Phase 2: Nivolumab+Ipilimumab+Binimetinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   10/10 (100.00%)   11/11 (100.00%)   27/27 (100.00%)   27/27 (100.00%) 
Blood and lymphatic system disorders         
Anaemia * 1  0/10 (0.00%)  1/11 (9.09%)  7/27 (25.93%)  4/27 (14.81%) 
Leukopenia * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Thrombocytopenia * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Cardiac disorders         
Cardiac failure * 1  0/10 (0.00%)  0/11 (0.00%)  2/27 (7.41%)  1/27 (3.70%) 
Ventricular hypokinesia * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Endocrine disorders         
Hypothyroidism * 1  1/10 (10.00%)  1/11 (9.09%)  0/27 (0.00%)  1/27 (3.70%) 
Eye disorders         
Visual impairment * 1  2/10 (20.00%)  1/11 (9.09%)  0/27 (0.00%)  3/27 (11.11%) 
Periorbital oedema * 1  1/10 (10.00%)  0/11 (0.00%)  3/27 (11.11%)  1/27 (3.70%) 
Vision blurred * 1  1/10 (10.00%)  1/11 (9.09%)  1/27 (3.70%)  1/27 (3.70%) 
Eyelid oedema * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  2/27 (7.41%) 
Subretinal fluid * 1  0/10 (0.00%)  0/11 (0.00%)  2/27 (7.41%)  1/27 (3.70%) 
Macular oedema * 1  0/10 (0.00%)  0/11 (0.00%)  2/27 (7.41%)  0/27 (0.00%) 
Photopsia * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  1/27 (3.70%) 
Retinopathy * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  2/27 (7.41%) 
Dry age-related macular degeneration * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Eye oedema * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Vitreous detachment * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Gastrointestinal disorders         
Diarrhoea * 1  6/10 (60.00%)  4/11 (36.36%)  13/27 (48.15%)  15/27 (55.56%) 
Nausea * 1  5/10 (50.00%)  2/11 (18.18%)  12/27 (44.44%)  11/27 (40.74%) 
Vomiting * 1  2/10 (20.00%)  8/11 (72.73%)  7/27 (25.93%)  10/27 (37.04%) 
Constipation * 1  2/10 (20.00%)  3/11 (27.27%)  9/27 (33.33%)  6/27 (22.22%) 
Abdominal pain * 1  1/10 (10.00%)  0/11 (0.00%)  5/27 (18.52%)  5/27 (18.52%) 
Dry mouth * 1  0/10 (0.00%)  1/11 (9.09%)  3/27 (11.11%)  5/27 (18.52%) 
Stomatitis * 1  1/10 (10.00%)  2/11 (18.18%)  3/27 (11.11%)  3/27 (11.11%) 
Abdominal distension * 1  0/10 (0.00%)  1/11 (9.09%)  3/27 (11.11%)  3/27 (11.11%) 
Dyspepsia * 1  1/10 (10.00%)  1/11 (9.09%)  1/27 (3.70%)  3/27 (11.11%) 
Gastrooesophageal reflux disease * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  5/27 (18.52%) 
Ascites * 1  0/10 (0.00%)  0/11 (0.00%)  4/27 (14.81%)  0/27 (0.00%) 
Abdominal discomfort * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  2/27 (7.41%) 
Abdominal pain upper * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  2/27 (7.41%) 
Abdominal pain lower * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  2/27 (7.41%) 
Haemorrhoids * 1  0/10 (0.00%)  1/11 (9.09%)  1/27 (3.70%)  0/27 (0.00%) 
Pancreatitis * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  2/27 (7.41%) 
Proctalgia * 1  0/10 (0.00%)  0/11 (0.00%)  2/27 (7.41%)  0/27 (0.00%) 
Colitis * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Glossitis * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Lower gastrointestinal haemorrhage * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Mesenteric arterial occlusion * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Small intestinal obstruction * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
General disorders         
Fatigue * 1  4/10 (40.00%)  6/11 (54.55%)  11/27 (40.74%)  11/27 (40.74%) 
Oedema peripheral * 1  5/10 (50.00%)  5/11 (45.45%)  8/27 (29.63%)  11/27 (40.74%) 
Pyrexia * 1  3/10 (30.00%)  3/11 (27.27%)  8/27 (29.63%)  14/27 (51.85%) 
Asthenia * 1  3/10 (30.00%)  1/11 (9.09%)  7/27 (25.93%)  9/27 (33.33%) 
Chills * 1  1/10 (10.00%)  1/11 (9.09%)  4/27 (14.81%)  4/27 (14.81%) 
Face oedema * 1  0/10 (0.00%)  1/11 (9.09%)  4/27 (14.81%)  1/27 (3.70%) 
Localised oedema * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  3/27 (11.11%) 
Influenza like illness * 1  0/10 (0.00%)  2/11 (18.18%)  1/27 (3.70%)  0/27 (0.00%) 
Infections and infestations         
Paronychia * 1  1/10 (10.00%)  1/11 (9.09%)  3/27 (11.11%)  3/27 (11.11%) 
Rash pustular * 1  1/10 (10.00%)  1/11 (9.09%)  2/27 (7.41%)  3/27 (11.11%) 
Urinary tract infection * 1  0/10 (0.00%)  1/11 (9.09%)  2/27 (7.41%)  0/27 (0.00%) 
Bronchitis * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  1/27 (3.70%) 
Folliculitis * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  2/27 (7.41%) 
Oral herpes * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  1/27 (3.70%) 
Conjunctivitis * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Pneumonia * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Staphylococcal bacteraemia * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Injury, poisoning and procedural complications         
Abdominal injury * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  2/27 (7.41%) 
Fall * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  1/27 (3.70%) 
Skin abrasion * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  1/27 (3.70%) 
Laceration * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Scratch * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Investigations         
Blood creatine phosphokinase increased * 1  5/10 (50.00%)  3/11 (27.27%)  14/27 (51.85%)  13/27 (48.15%) 
Aspartate aminotransferase increased * 1  0/10 (0.00%)  3/11 (27.27%)  2/27 (7.41%)  9/27 (33.33%) 
Alanine aminotransferase increased * 1  0/10 (0.00%)  2/11 (18.18%)  2/27 (7.41%)  8/27 (29.63%) 
Ejection fraction decreased * 1  1/10 (10.00%)  0/11 (0.00%)  4/27 (14.81%)  7/27 (25.93%) 
Blood alkaline phosphatase increased * 1  1/10 (10.00%)  0/11 (0.00%)  1/27 (3.70%)  5/27 (18.52%) 
Amylase increased * 1  0/10 (0.00%)  0/11 (0.00%)  3/27 (11.11%)  3/27 (11.11%) 
Blood bilirubin increased * 1  0/10 (0.00%)  0/11 (0.00%)  2/27 (7.41%)  2/27 (7.41%) 
Lipase increased * 1  0/10 (0.00%)  0/11 (0.00%)  2/27 (7.41%)  2/27 (7.41%) 
Gamma-glutamyltransferase increased * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  2/27 (7.41%) 
Troponin T increased * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  3/27 (11.11%) 
Weight decreased * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  2/27 (7.41%) 
Platelet count decreased * 1  0/10 (0.00%)  0/11 (0.00%)  2/27 (7.41%)  0/27 (0.00%) 
Troponin I increased * 1  1/10 (10.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
Electrocardiogram abnormal * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Intraocular pressure increased * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Prothrombin time prolonged * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Metabolism and nutrition disorders         
Decreased appetite * 1  2/10 (20.00%)  3/11 (27.27%)  13/27 (48.15%)  6/27 (22.22%) 
Hypokalaemia * 1  2/10 (20.00%)  1/11 (9.09%)  3/27 (11.11%)  2/27 (7.41%) 
Hypomagnesaemia * 1  1/10 (10.00%)  0/11 (0.00%)  1/27 (3.70%)  2/27 (7.41%) 
Dehydration * 1  1/10 (10.00%)  1/11 (9.09%)  0/27 (0.00%)  1/27 (3.70%) 
Hyperglycaemia * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  2/27 (7.41%) 
Hypoalbuminaemia * 1  0/10 (0.00%)  0/11 (0.00%)  2/27 (7.41%)  1/27 (3.70%) 
Hyponatraemia * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  2/27 (7.41%) 
Hypophosphataemia * 1  0/10 (0.00%)  0/11 (0.00%)  2/27 (7.41%)  1/27 (3.70%) 
Hypocalcaemia * 1  0/10 (0.00%)  1/11 (9.09%)  1/27 (3.70%)  0/27 (0.00%) 
Hyperuricaemia * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back pain * 1  0/10 (0.00%)  0/11 (0.00%)  5/27 (18.52%)  4/27 (14.81%) 
Myalgia * 1  0/10 (0.00%)  2/11 (18.18%)  3/27 (11.11%)  1/27 (3.70%) 
Arthralgia * 1  1/10 (10.00%)  0/11 (0.00%)  1/27 (3.70%)  2/27 (7.41%) 
Neck pain * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  2/27 (7.41%) 
Muscular weakness * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  1/27 (3.70%) 
Pain in extremity * 1  1/10 (10.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
Musculoskeletal chest pain * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Tumour associated fever * 1  1/10 (10.00%)  0/11 (0.00%)  2/27 (7.41%)  0/27 (0.00%) 
Basal cell carcinoma * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Cancer pain * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Nervous system disorders         
Dysgeusia * 1  1/10 (10.00%)  2/11 (18.18%)  1/27 (3.70%)  2/27 (7.41%) 
Dizziness * 1  0/10 (0.00%)  2/11 (18.18%)  2/27 (7.41%)  0/27 (0.00%) 
Neuropathy peripheral * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  2/27 (7.41%) 
Headache * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  2/27 (7.41%) 
Syncope * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Psychiatric disorders         
Depression * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  2/27 (7.41%) 
Confusional state * 1  0/10 (0.00%)  2/11 (18.18%)  0/27 (0.00%)  0/27 (0.00%) 
Insomnia * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Renal and urinary disorders         
Haematuria * 1  1/10 (10.00%)  0/11 (0.00%)  2/27 (7.41%)  0/27 (0.00%) 
Proteinuria * 1  0/10 (0.00%)  0/11 (0.00%)  1/27 (3.70%)  2/27 (7.41%) 
Chromaturia * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  2/27 (7.41%) 
Renal colic * 1  0/10 (0.00%)  1/11 (9.09%)  1/27 (3.70%)  0/27 (0.00%) 
Reproductive system and breast disorders         
Benign prostatic hyperplasia * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Pruritus genital * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Scrotal oedema * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Cough * 1  2/10 (20.00%)  3/11 (27.27%)  6/27 (22.22%)  6/27 (22.22%) 
Dyspnoea * 1  0/10 (0.00%)  4/11 (36.36%)  4/27 (14.81%)  4/27 (14.81%) 
Pneumonitis * 1  0/10 (0.00%)  2/11 (18.18%)  1/27 (3.70%)  1/27 (3.70%) 
Dysphonia * 1  0/10 (0.00%)  0/11 (0.00%)  3/27 (11.11%)  0/27 (0.00%) 
Epistaxis * 1  1/10 (10.00%)  0/11 (0.00%)  1/27 (3.70%)  1/27 (3.70%) 
Productive cough * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  2/27 (7.41%) 
Rales * 1  0/10 (0.00%)  2/11 (18.18%)  1/27 (3.70%)  0/27 (0.00%) 
Wheezing * 1  0/10 (0.00%)  0/11 (0.00%)  2/27 (7.41%)  0/27 (0.00%) 
Dyspnoea exertional * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Nasal congestion * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Skin and subcutaneous tissue disorders         
Dermatitis acneiform * 1  7/10 (70.00%)  6/11 (54.55%)  13/27 (48.15%)  12/27 (44.44%) 
Rash * 1  3/10 (30.00%)  1/11 (9.09%)  8/27 (29.63%)  14/27 (51.85%) 
Pruritus * 1  0/10 (0.00%)  3/11 (27.27%)  5/27 (18.52%)  7/27 (25.93%) 
Dry skin * 1  1/10 (10.00%)  2/11 (18.18%)  2/27 (7.41%)  5/27 (18.52%) 
Rash maculo-papular * 1  1/10 (10.00%)  1/11 (9.09%)  3/27 (11.11%)  0/27 (0.00%) 
Alopecia * 1  0/10 (0.00%)  0/11 (0.00%)  2/27 (7.41%)  2/27 (7.41%) 
Erythema * 1  1/10 (10.00%)  1/11 (9.09%)  0/27 (0.00%)  2/27 (7.41%) 
Pruritus generalised * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  2/27 (7.41%) 
Rash macular * 1  0/10 (0.00%)  0/11 (0.00%)  2/27 (7.41%)  1/27 (3.70%) 
Rash papular * 1  0/10 (0.00%)  1/11 (9.09%)  1/27 (3.70%)  1/27 (3.70%) 
Rash pruritic * 1  2/10 (20.00%)  0/11 (0.00%)  1/27 (3.70%)  0/27 (0.00%) 
Acne * 1  0/10 (0.00%)  0/11 (0.00%)  0/27 (0.00%)  2/27 (7.41%) 
Dermatitis * 1  1/10 (10.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Hyperhidrosis * 1  0/10 (0.00%)  0/11 (0.00%)  2/27 (7.41%)  0/27 (0.00%) 
Dermatitis exfoliative generalised * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Ecchymosis * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Exfoliative rash * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Petechiae * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Rash erythematous * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Skin fissures * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Skin hyperpigmentation * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Skin lesion * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Skin reaction * 1  0/10 (0.00%)  1/11 (9.09%)  0/27 (0.00%)  0/27 (0.00%) 
Urticaria * 1  1/10 (10.00%)  0/11 (0.00%)  0/27 (0.00%)  0/27 (0.00%) 
Vascular disorders         
Hypertension * 1  0/10 (0.00%)  1/11 (9.09%)  3/27 (11.11%)  4/27 (14.81%) 
Hypotension * 1  1/10 (10.00%)  0/11 (0.00%)  1/27 (3.70%)  1/27 (3.70%) 
1
Term from vocabulary, MedDRA v21.0
*
Indicates events were collected by non-systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03271047    
Other Study ID Numbers: ARRAY-162-202
C4211004 ( Other Identifier: Alias Study Number )
2017-003464-12 ( EudraCT Number )
First Submitted: August 31, 2017
First Posted: September 1, 2017
Results First Submitted: October 4, 2021
Results First Posted: November 2, 2021
Last Update Posted: January 4, 2022