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Trial record 1 of 1 for:    NCT02584634
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Study to Evaluate Safety, Efficacy, Pharmacokinetics And Pharmacodynamics Of Avelumab In Combination With Either Crizotinib Or PF-06463922 In Patients With NSCLC. (Javelin Lung 101)

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ClinicalTrials.gov Identifier: NCT02584634
Recruitment Status : Terminated (The study was terminated since there was no need for further safety or efficacy data to be collected. The participants having benefit from the Investigational treatments have been moved to a continuation study (NCT05059522))
First Posted : October 22, 2015
Results First Posted : February 9, 2022
Last Update Posted : July 7, 2023
Sponsor:
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
Condition Non-Small Cell Lung Cancer
Interventions Drug: Avelumab
Drug: PF-06463922
Drug: Crizotinib
Enrollment 43
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Group A: Avelumab + Crizotinib Group B: Avelumab + Lorlatinib
Hide Arm/Group Description Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule. Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Period Title: Overall Study
Started 12 31
Completed 0 0
Not Completed 12 31
Reason Not Completed
Adverse Event             3             5
Death             0             1
Lost to Follow-up             0             1
Physician Decision             1             2
Progressive disease             7             15
Withdrawal by Subject             1             1
Other             0             6
Arm/Group Title Group A: Avelumab + Crizotinib Group B: Avelumab + Lorlatinib Total
Hide Arm/Group Description Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule. Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule. Total of all reporting groups
Overall Number of Baseline Participants 12 31 43
Hide Baseline Analysis Population Description
The baseline analysis population included all participants who received at least one dose of study drug. Participants were classified according to the study treatment actually received. If a participant received more than one treatment the participant was classified according to the first treatment received.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 31 participants 43 participants
58.67  (10.43) 53.32  (11.59) 54.81  (11.41)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 12 participants 31 participants 43 participants
<65 years 9 25 7
65-<75 years 2 5 2
75-<85 years 1 1 2
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 31 participants 43 participants
Female
6
  50.0%
19
  61.3%
25
  58.1%
Male
6
  50.0%
12
  38.7%
18
  41.9%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 12 participants 31 participants 43 participants
American Indian or Alaska Native 0 1 1
Asian 8 17 25
White 4 13 17
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 12 participants 31 participants 43 participants
Hispanic or Latino 0 1 1
Not Hispanic or Latino 11 30 41
Not Reported 1 0 1
Age Range  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 12 participants 31 participants 43 participants
59.5
(43 to 76)
54
(30 to 77)
55
(30 to 77)
1.Primary Outcome
Title Number of Participants With Dose-limiting Toxicities (DLTs): Phase 1b
Hide Description Any of the following adverse events (AEs) occurring during the primary DLT observation period that are attributable to one, the other, or both study drugs were classified as DLTs: Grade 4 (life-threatening) neutropenia if >7 days in duration; febrile neutropenia; Grade >=3 (severe or life threatening) neutropenic infection; Grade >=3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia >7 days; Grade 4 anemia; any Grade >=3 toxicity, except for any of the following: transient (<=6 hours) Grade 3 (severe) flu like symptoms or fever; transient (<=24 hours) Grade 3 fatigue, local reactions, or headache that resolved to Grade <=1 (no AE or mild AE); Grade 3 nausea and/or vomiting, diarrhea or skin toxicity that resolved to Grade <=1 within 7 days; any Grade >=3 amylase or lipase abnormality; tumor flare phenomenon; single laboratory values out of normal range that were not related to treatment, did not have any clinical correlate, and resolve to Grade <=1 within 7 days.
Time Frame First 2 cycles (1 cycle = 14 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants enrolled in Phase 1b who were in the safety analysis set (all participants who received at least one dose of study drug), and either experienced DLT during the first 2 cycles (1 cycle = 14 days), or completed the observation period for the first 2 cycles of treatment.
Arm/Group Title Group A: Avelumab + Crizotinib Group B: Avelumab + Lorlatinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 12 28
Measure Type: Count of Participants
Unit of Measure: Participants
5
  41.7%
2
   7.1%
2.Primary Outcome
Title Percentage of Participants With Objective Response (OR): Phase 2
Hide Description OR is defined as complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 from start date (the date of first dose of study treatment) until disease progression or death due to any cause. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met. Per RECIST v1.1: CR is defined as the disappearance of all target or non-target lesions; any pathological lymph nodes (whether target or non target) must have reduction in short axis to <10 mm and all lymph nodes must be non-pathological in size (<10 mm short axis). PR is defined as a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Time Frame Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received at least one dose of study drug. Participants were classified according to the study treatment actually received. If a participant received more than one treatment the participant was classified according to the first treatment received.
Arm/Group Title Group A: Avelumab + Crizotinib Group B: Avelumab + Lorlatinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 12 31
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
25.0
(5.5 to 57.2)
51.6
(33.1 to 69.8)
3.Primary Outcome
Title Percentage of Participants With CR for Group B: Phase 2
Hide Description Per RECIST v1.1: CR is defined as the disappearance of all target or non-target lesions; any pathological lymph nodes (whether target or non target) must have reduction in short axis to <10 mm and all lymph nodes must be non-pathological in size (<10 mm short axis).
Time Frame Baseline up to 60 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received at least one dose of study drug in Group B. Participants were classified according to the study treatment actually received. If a participant received more than one treatment the participant was classified according to the first treatment received. Results for Group A are not reported for this outcome measure according to the protocol.
Arm/Group Title Group B: Avelumab + Lorlatinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 31
Measure Type: Number
Unit of Measure: Percentage of participants
3.2
4.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Hide Description TEAEs are those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event is during the on-treatment period. Treatment-related AEs was any untoward medical occurrence attributed to study drug in a participant who received study drug. Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03: Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment; Grade 4 (Life-threatening) events caused participant to be in imminent danger of death; Grade 5 (Death) events=death related to an AE. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in participant hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time Frame Baseline up to 30 days after last dose of study treatment or the day before start day of new anti-cancer therapy (maximum of 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received at least one dose of study drug. Participants were classified according to the study treatment actually received. If a participant received more than one study treatment, the participant were classified according to the first treatment received.
Arm/Group Title Group A: Avelumab + Crizotinib Group B: Avelumab + Lorlatinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 12 31
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with TEAEs Number Analyzed 12 participants 31 participants
12
 100.0%
30
  96.8%
Participants with Grade >= 3 TEAEs Number Analyzed 12 participants 31 participants
7
  58.3%
23
  74.2%
Participants with treatment-related TEAEs Number Analyzed 12 participants 31 participants
12
 100.0%
28
  90.3%
Participants with Grade >= 3 treatment-related TEAEs Number Analyzed 12 participants 31 participants
6
  50.0%
16
  51.6%
Participants with SAEs Number Analyzed 12 participants 31 participants
5
  41.7%
21
  67.7%
Participants with treatment-related SAEs Number Analyzed 12 participants 31 participants
2
  16.7%
6
  19.4%
Participants with TEAEs leading to discontinuation of avelumab Number Analyzed 12 participants 31 participants
3
  25.0%
10
  32.3%
Participants with TEAEs leading to discontinuation of crizotinib Number Analyzed 12 participants 0 participants
6
  50.0%
Participants with TEAEs leading to discontinuation of lorlatinib Number Analyzed 0 participants 31 participants
2
   6.5%
Participants with TEAEs leading to discontinuation of any study drug Number Analyzed 12 participants 31 participants
6
  50.0%
10
  32.3%
Participants with TEAEs leading to discontinuation of all study drugs Number Analyzed 12 participants 31 participants
3
  25.0%
1
   3.2%
Participants with treatment-related TEAEs leading to discontinuation of avelumab Number Analyzed 12 participants 31 participants
2
  16.7%
9
  29.0%
Participants with treatment-related TEAEs leading to discontinuation of crizotinib Number Analyzed 12 participants 0 participants
5
  41.7%
Participants with treatment-related TEAEs leading to discontinuation of lorlatinib Number Analyzed 0 participants 31 participants
2
   6.5%
Participants with TEAEs leading to death Number Analyzed 12 participants 31 participants
1
   8.3%
4
  12.9%
Participants with treatment-related TEAEs leading to death Number Analyzed 12 participants 31 participants
0
   0.0%
1
   3.2%
Participants with infusion-related reactions Number Analyzed 12 participants 31 participants
5
  41.7%
9
  29.0%
5.Secondary Outcome
Title Number of Participants With Baseline Laboratory Abnormalities Grade <=2 and Post-Baseline Laboratory Abnormalities of Grades 3 or 4 Per NCI CTCAE v4.03
Hide Description The laboratory results were graded according to the NCI CTCAE v4.03 severity grade. Grade 1=mild AE. Grade 2=moderate AE. Grade 3=severe AE. Grade 4=life-threatening consequences; urgent intervention indicated. Shift tables were provided to examine the distribution of laboratory toxicities. The following parameters had met the criteria of CTCAE grade shift change from Grade <=2 at baseline to Grade 3 or 4 post baseline: anemia, lymphocyte count decreased, lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, alanine aminotransferase increased, aspartate aminotransferase increased, blood bilirubin increased, cholesterol high, Creatine phosphokinase (CPK) increased, Gamma glutamyl transferase (GGT) increased, hypercalcemia, hyperglycemia, hypermagnesemia, hypertriglyceridemia, hypoalbuminemia, hyponatremia, lipase increased, serum amylase increased. Baseline is defined as the last assessment prior to the date/time of the first dose of study treatment.
Time Frame Screening up to end of treatment/withdrawal (maximum of 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received at least one dose of study drug and who could be evaluated for CTCAE criteria for each parameter in each treatment group. Participants were classified according to the study treatment actually received. If a participant received more than one study treatment, the participant was classified according to the first treatment received.
Arm/Group Title Group A: Avelumab + Crizotinib Group B: Avelumab + Lorlatinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 12 31
Measure Type: Count of Participants
Unit of Measure: Participants
Anemia Number Analyzed 12 participants 31 participants
0
   0.0%
3
   9.7%
Lymphocyte count decreased Number Analyzed 12 participants 31 participants
1
   8.3%
2
   6.5%
Lymphocyte count increased Number Analyzed 12 participants 31 participants
0
   0.0%
2
   6.5%
Neutrophil count decreased Number Analyzed 12 participants 31 participants
1
   8.3%
0
   0.0%
White blood cell decreased Number Analyzed 12 participants 31 participants
1
   8.3%
0
   0.0%
Alanine aminotransferase increased Number Analyzed 12 participants 31 participants
3
  25.0%
0
   0.0%
Aspartate aminotransferase increased Number Analyzed 12 participants 31 participants
2
  16.7%
1
   3.2%
Blood bilirubin increased Number Analyzed 12 participants 31 participants
0
   0.0%
1
   3.2%
Cholesterol high Number Analyzed 12 participants 31 participants
0
   0.0%
5
  16.1%
CPK increased Number Analyzed 10 participants 31 participants
0
   0.0%
2
   6.5%
GGT increased Number Analyzed 12 participants 31 participants
1
   8.3%
5
  16.1%
Hypercalcemia Number Analyzed 12 participants 31 participants
0
   0.0%
2
   6.5%
Hyperglycemia Number Analyzed 12 participants 31 participants
1
   8.3%
1
   3.2%
Hypermagnesemia Number Analyzed 12 participants 31 participants
0
   0.0%
1
   3.2%
Hypertriglyceridemia Number Analyzed 12 participants 31 participants
0
   0.0%
7
  22.6%
Hypoalbuminemia Number Analyzed 12 participants 31 participants
0
   0.0%
1
   3.2%
Hyponatremia Number Analyzed 12 participants 31 participants
1
   8.3%
3
   9.7%
Lipase increased Number Analyzed 12 participants 31 participants
1
   8.3%
5
  16.1%
Serum amylase increased Number Analyzed 12 participants 31 participants
0
   0.0%
1
   3.2%
Hemoglobin increased Number Analyzed 12 participants 31 participants
0
   0.0%
0
   0.0%
Platelet count decreased Number Analyzed 12 participants 31 participants
0
   0.0%
0
   0.0%
Alkaline phosphatase increased Number Analyzed 12 participants 31 participants
0
   0.0%
0
   0.0%
Creatinine increased Number Analyzed 12 participants 31 participants
0
   0.0%
0
   0.0%
Hyperkalemia Number Analyzed 12 participants 31 participants
0
   0.0%
0
   0.0%
Hypernatremia Number Analyzed 12 participants 31 participants
0
   0.0%
0
   0.0%
Hypocalcemia Number Analyzed 12 participants 31 participants
0
   0.0%
0
   0.0%
Hypoglycemia Number Analyzed 12 participants 31 participants
0
   0.0%
0
   0.0%
Hypokalemia Number Analyzed 12 participants 31 participants
0
   0.0%
0
   0.0%
Hypomagnesemia Number Analyzed 12 participants 31 participants
0
   0.0%
0
   0.0%
Hypophosphatemia Number Analyzed 12 participants 31 participants
0
   0.0%
0
   0.0%
6.Secondary Outcome
Title Number of Participants With Vital Signs Meeting Pre-defined Criteria
Hide Description Pre-defined criteria in vital signs: pulse rate <50 beats per minute, pulse rate >120 bpm, sitting diastolic blood pressure (DBP) increase and decrease in change from baseline of >= 20 millimeter of mercury (mmHg), sitting systolic blood pressure(SBP) < 90 mmHg, increase and decrease in change from baseline of >= 30mmHg. Baseline is defined as the last assessment prior to the date/time of the first dose of study treatment.
Time Frame Screening up to end of treatment/withdrawal (maximum of 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received at least one dose of study drug. Participants were classified according to the study treatment actually received. If a participant received more than one study treatment, the participant was classified according to the first treatment received.
Arm/Group Title Group A: Avelumab + Crizotinib Group B: Avelumab + Lorlatinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 12 31
Measure Type: Count of Participants
Unit of Measure: Participants
Pulse rate <50 bpm
2
  16.7%
0
   0.0%
Pulse rate >120 bpm
0
   0.0%
4
  12.9%
Sitting DBP change >= 20 mmHg increase
2
  16.7%
13
  41.9%
Sitting DBP change >= 20 mmHg decrease
5
  41.7%
8
  25.8%
Sitting SBP <90 mmHg
1
   8.3%
4
  12.9%
Sitting SBP change >= 30 mmHg increase
1
   8.3%
11
  35.5%
Sitting SBP change >= 30 mmHg decrease
3
  25.0%
2
   6.5%
7.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description DC is defined as objective response (CR or PR) or stable disease (SD) per RECIST v.1.1 from the date of first dose of study treatment until disease progression or death due to any cause. The DCR is the proportion of patients with DC. Per RECIST v1.1: CR is defined as the disappearance of all target or non-target lesions; any pathological lymph nodes (whether target or non target) must have reduction in short axis to <10 mm. PR is defined as a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD is defined as a >=20% increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions.
Time Frame Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received at least one dose of study drug. Participants were classified according to the study treatment actually received. If a participant received more than one treatment the participant was classified according to the first treatment received.
Arm/Group Title Group A: Avelumab + Crizotinib Group B: Avelumab + Lorlatinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 12 31
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
58.3
(27.7 to 84.8)
71.0
(52.0 to 85.8)
8.Secondary Outcome
Title Duration of Response (DR)
Hide Description DR: time from first documented occurrence of response (PR or CR) until date of first documented PD or death due to underlying cancer. Per RECIST 1.1: CR: disappearance of all non-nodal target lesions and of all non-target lesions; any pathological lymph nodes assigned as target lesions/non-target lesions have a reduction in short axis to <10 mm. PR: at least a >=30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters. PD: at least a >=20% increase in sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. Appearance of new lesions. Participants with no PD and were still alive by 02 Feb 2020, were censored at last adequate tumor assessment. Kaplan-Meier method was used for DR analysis.
Time Frame Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received at least one dose of study drug and who had confirmed complete response or partial response. Participants were classified according to the study treatment actually received. If a participant received more than one treatment the participant was classified according to the first treatment received.
Arm/Group Title Group A: Avelumab + Crizotinib Group B: Avelumab + Lorlatinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 3 16
Median (95% Confidence Interval)
Unit of Measure: Month
3.7
(3.7 to 4.6)
14.7 [1] 
(3.7 to NA)
[1]
The upper bound of the 95% confidence interval was not estimable due to limited number of events.
9.Secondary Outcome
Title Time to Tumor Response (TTR)
Hide Description TTR is defined, for participants with an objective response (CR or PR), as the time from the start date (the date of first dose of treatment) to the first documentation of objective response (CR or PR) which is subsequently confirmed. Per RECIST v1.1: CR: disappearance of all non-nodal target lesions and of all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions/ non-target lesions must have a reduction in short axis to <10 mm. PR: at least a 30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters.
Time Frame Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received at least one dose of study drug and who had confirmed complete response or partial response. Participants were classified according to the study treatment actually received. If a participant received more than one treatment the participant was classified according to the first treatment received.
Arm/Group Title Group A: Avelumab + Crizotinib Group B: Avelumab + Lorlatinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 3 16
Median (Full Range)
Unit of Measure: Months
1.4
(1.4 to 6.9)
1.8
(1.3 to 3.7)
10.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description PFS is defined as the time from start date (the date of first dose of treatment) to the date of the first documentation of PD per RECIST v1.1 or death due to any cause, whichever occurs first. Per RECIST v1.1: PD: a >=20% increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years)
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Hide Analysis Population Description
The analysis population included all participants who received at least one dose of study drug. Participants were classified according to the study treatment actually received. If a participant received more than one treatment the participant was classified according to the first treatment received.
Arm/Group Title Group A: Avelumab + Crizotinib Group B: Avelumab + Lorlatinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 12 31
Median (95% Confidence Interval)
Unit of Measure: Months
3.7
(1.5 to 5.5)
6.4
(3.7 to 9.2)
11.Secondary Outcome
Title Kaplan-Meier Estimates of Overall Survival (OS)
Hide Description OS is defined as the time from start date (the date of first dose of treatment) to the date of death due to any cause.
Time Frame Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received at least one dose of study drug. Participants were classified according to the study treatment actually received. If a participant received more than one treatment the participant was classified according to the first treatment received.
Arm/Group Title Group A: Avelumab + Crizotinib Group B: Avelumab + Lorlatinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 12 31
Median (95% Confidence Interval)
Unit of Measure: Months
16.4
(5.4 to 27.6)
32.9 [1] 
(10.7 to NA)
[1]
The upper bound of the 95% confidence interval was not estimable due to limited number of events.
12.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of Crizotinib in The Presence of Avelumab
Hide Description Cmax of crizotinib in the presence of avelumab was observed directly from data.
Time Frame Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included participants who received at least one dose of study drug and who had at least one of the pharmacokinetic (PK) parameters of interest for crizotinib in Group A. Group B was not evaluable for this outcome measure.
Arm/Group Title Group A: Avelumab + Crizotinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms per millilitre (ng/mL)
281
(74%)
13.Secondary Outcome
Title Time to Cmax (Tmax) of Crizotinib in The Presence of Avelumab
Hide Description Tmax of crizotinib in the presence of avelumab was observed directly from data as time of first occurrence.
Time Frame Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included participants who received at least one dose of study drug and who had at least one of the PK parameters of interest for crizotinib in Group A. Group B was not evaluable for this outcome measure.
Arm/Group Title Group A: Avelumab + Crizotinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 10
Median (Full Range)
Unit of Measure: Hours
2.03
(0.00 to 8.08)
14.Secondary Outcome
Title Area Under The Plasma Concentration-Time Curve During The Dosing Interval Time Course (AUCtau) of Crizotinib in The Presence of Avelumab
Hide Description AUCtau of crizotinib in the presence of avelumab was calculated by Linear/Log trapezoidal method. Dose interval is defined as after single dose from time zero to the next dose (after single dose and at steady state).
Time Frame Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included participants who received at least one dose of study drug and who had at least one of the PK parameters of interest for crizotinib in Group A. Group B was not evaluable for this outcome measure.
Arm/Group Title Group A: Avelumab + Crizotinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms*hours per millilitre (ng*h/mL)
2755
(82%)
15.Secondary Outcome
Title Apparent Plasma Clearance (CL/F) of Crizotinib in The Presence of Avelumab
Hide Description Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time Frame Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included participants who received at least one dose of study drug and who had at least one of the PK parameters of interest for crizotinib in Group A. Group B was not evaluable for this outcome measure.
Arm/Group Title Group A: Avelumab + Crizotinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liter per hour (L/h)
90.76
(82%)
16.Secondary Outcome
Title Cmax of Crizotinib Metabolite PF-06260182 in The Presence of Avelumab
Hide Description Cmax of crizotinib metabolite PF-06260182 in the presence of avelumab was observed directly from data.
Time Frame Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included participants who received at least one dose of study drug and who had at least one of the PK parameters of interest for crizotinib in Group A. Group B was not evaluable for this outcome measure.
Arm/Group Title Group A: Avelumab + Crizotinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
84.11
(91%)
17.Secondary Outcome
Title Tmax of Crizotinib Metabolite PF-06260182 in The Presence of Avelumab
Hide Description Tmax of crizotinib metabolite PF-06260182 in the presence of avelumab was observed directly from data as time of first occurrence.
Time Frame Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included participants who received at least one dose of study drug and who had at least one of the PK parameters of interest for crizotinib in Group A. Group B was not evaluable for this outcome measure.
Arm/Group Title Group A: Avelumab + Crizotinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 10
Median (Full Range)
Unit of Measure: Hours
3.02
(0.00 to 8.08)
18.Secondary Outcome
Title AUCtau of Crizotinib Metabolite PF-06260182 in The Presence of Avelumab
Hide Description AUCtau of crizotinib metabolite PF-06260182 in the presence of avelumab was calculated by Linear/Log trapezoidal method. Dose interval: single dose from time zero to the next dose (after single dose and at steady state).
Time Frame Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included participants who received at least one dose of study drug and who had at least one of the PK parameters of interest for crizotinib in Group A. Group B was not evaluable for this outcome measure.
Arm/Group Title Group A: Avelumab + Crizotinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
789.1
(116%)
19.Secondary Outcome
Title Metabolite to Parent Ratio for AUCtau (MRAUCtau) of PF-06260182 in The Presence of Avelumab
Hide Description MRAUCtau of metabolite PF-06260182 in the presence of avelumab was calculated (MRAUCtau=Metabolite AUCtau/parent AUCtau). Parent=crizotinib, metabolite=PF-06260182
Time Frame Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included participants who received at least one dose of study drug and who had at least one of the PK parameters of interest for crizotinib in Group A. Group B was not evaluable for this outcome measure.
Arm/Group Title Group A: Avelumab + Crizotinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio
0.2779
(33%)
20.Secondary Outcome
Title Metabolite to Parent Ratio for Cmax (MRCmax) of PF-06260182 in The Presence of Avelumab
Hide Description MRCmax of metabolite PF-06260182 in the presence of avelumab was calculated (MRCmax=Metabolite Cmax/parent Cmax). Parent=crizotinib, metabolite=PF-06260182
Time Frame Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included participants who received at least one dose of study drug and who had at least one of the PK parameters of interest for crizotinib in Group A. Group B was not evaluable for this outcome measure.
Arm/Group Title Group A: Avelumab + Crizotinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio
0.2902
(25%)
21.Secondary Outcome
Title Cmax of Lorlatinib in The Presence of Avelumab
Hide Description Cmax of lorlatinib in the presence of avelumab was observed directly from data.
Time Frame Pre-dose, 1, 2, 4, 6, 8, and 24 hours (prior to Day 2 lorlatinib dose) post dose on Day 1 of Cycle 2
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included participants who received at least one dose of study drug and who had at least one of the PK parameters of interest for lorlatinib in Group B. Group A is not evaluable for this outcome measure.
Arm/Group Title Group B: Avelumab + Lorlatinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
596.9
(33%)
22.Secondary Outcome
Title Tmax of Lorlatinib in The Presence of Avelumab
Hide Description Tmax of lorlatinib in the presence of avelumab was observed directly from data.
Time Frame Pre-dose, 1, 2, 4, 6, 8, and 24 hours (prior to Day 2 lorlatinib dose) post dose on Day 1 of Cycle 2
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included participants who received at least one dose of study drug and who had at least one of the PK parameters of interest for lorlatinib in Group B. Group A is not evaluable for this outcome measure.
Arm/Group Title Group B: Avelumab + Lorlatinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 26
Median (Full Range)
Unit of Measure: Hours
1.23
(0.933 to 4.33)
23.Secondary Outcome
Title AUCtau of Lorlatinib in The Presence of Avelumab
Hide Description AUCtau of lorlatinib in the presence of avelumab was calculated by Linear/Log trapezoidal method. Dose interval: single dose from time zero to the next dose (after single dose and at steady state).
Time Frame Pre-dose, 1, 2, 4, 6, 8, and 24 hours (prior to Day 2 lorlatinib dose) post dose on Day 1 of Cycle 2
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included participants who received at least one dose of study drug and who had at least one of the PK parameters of interest for lorlatinib in Group B. Group A is not evaluable for this outcome measure.
Arm/Group Title Group B: Avelumab + Lorlatinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 19
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
5807
(42%)
24.Secondary Outcome
Title Area Under The Plasma Concentration Time Curve From Time of Dosing to The Last Collection Time Point (AUClast) of Lorlatinib in The Presence of Avelumab
Hide Description AUClast of lorlatinib in the presence of avelumab.
Time Frame Pre-dose, 1, 2, 4, 6, 8, and 24 hours (prior to Day 2 lorlatinib dose) post dose on Day 1 of Cycle 2
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included participants who received at least one dose of study drug and who had at least one of the PK parameters of interest for lorlatinib in Group B. Group A is not evaluable for this outcome measure.
Arm/Group Title Group B: Avelumab + Lorlatinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
4872
(52%)
25.Secondary Outcome
Title CL/F of Lorlatinib in The Presence of Avelumab
Hide Description Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time Frame Pre-dose, 1, 2, 4, 6, 8, and 24 hours (prior to Day 2 lorlatinib dose) post dose on Day 1 of Cycle 2
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included participants who received at least one dose of study drug and who had at least one of the PK parameters of interest for lorlatinib in Group B. Group A is not evaluable for this outcome measure.
Arm/Group Title Group B: Avelumab + Lorlatinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 19
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/h
16.97
(44%)
26.Secondary Outcome
Title Cmax of Avelumab in The Presence of Crizotinib (Group A) or Lorlatinib (Group B) After Single Dose of Avelumab
Hide Description Cmax of avelumab in the presence of crizotinib was observed directly from the data in Group A. Cmax of avelumab in the presence of lorlatinib was observed directly from the data in Group B.
Time Frame Pre-dose, 1, and 168 hours post dose of avelumab on Cycle 1 Day 1.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included participants who received at least one dose of study drug and who had at least one post-dose concentration measurement above the lower limit of quantification for avelumab.
Arm/Group Title Group A: Avelumab + Crizotinib Group B: Avelumab + Lorlatinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 8 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: micrograms/milliliter (ug/mL)
193.2
(14%)
195.7
(28%)
27.Secondary Outcome
Title Cmax of Avelumab in The Presence of Crizotinib (Group A) or Lorlatinib (Group B) After Multiple Doses of Avelumab
Hide Description Cmax of avelumab in the presence of crizotinib was observed directly from the data in Group A. Cmax of avelumab in the presence of lorlatinib was observed directly from the data in Group B.
Time Frame Pre-dose, 1, and 168 hours post dose of avelumab on Cycle 2 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included participants who received at least one dose of study drug and who had at least one post-dose concentration measurement above the lower limit of quantification for avelumab.
Arm/Group Title Group A: Avelumab + Crizotinib Group B: Avelumab + Lorlatinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 8 17
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ug/mL
174.5
(35%)
169.4
(68%)
28.Secondary Outcome
Title Trough Serum Concentration (Ctrough) of Avelumab in The Presence of Crizotinib (Group A) Following Multiple Doses of Avelumab
Hide Description Ctrough is defined as predose concentration following multiple doses. Ctrough of avelumab in the presence of crizotinib was observed directly from the data in Group A.
Time Frame Pre-dose on Day 1 of Cycles 2-5, 11, 17, 23, 29, 35, and 47.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included participants who received at least one dose of study drug and who had least one observation. Number of Participants Analyzed represents the total number of participants in the analysis population for this outcome measure. Number Analyzed represents the number of participants with concentration measurement above lower limit of quantification at each visit. Group B was not evaluable for this outcome measure.
Arm/Group Title Group A: Avelumab + Crizotinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ug/mL
Cycle 2 Day 1 Number Analyzed 7 participants
11.76
(68%)
Cycle 3 Day 1 Number Analyzed 6 participants
16.26
(53%)
Cycle 4 Day 1 Number Analyzed 7 participants
16.71
(34%)
Cycle 5 Day 1 Number Analyzed 5 participants
14.21
(46%)
Cycle 11 Day 1 Number Analyzed 2 participants
26.64
(4%)
Cycle 17 Day 1 Number Analyzed 2 participants
30.59
(9%)
Cycle 23 Day 1 Number Analyzed 2 participants
30.63
(15%)
Cycle 29 Day 1 Number Analyzed 2 participants
30.72
(55%)
Cycle 35 Day 1 Number Analyzed 2 participants
37.31
(27%)
Cycle 47 Day 1 Number Analyzed 2 participants
40.91
(15%)
29.Secondary Outcome
Title Trough Serum Concentration (Ctrough) of Avelumab in The Presence of Lorlatinib (Group B) Following Multiple Doses of Avelumab
Hide Description Ctrough is defined as predose concentration following multiple doses. Ctrough of avelumab in the presence of lorlatinib was observed directly from the data in Group B.
Time Frame Pre-dose on Day 1 of Cycles 2-5, 11, 17, 23, 29, 35, 41, and 47.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included participants who received at least one dose of study drug and who had least one observation. Number of Participants Analyzed represents the total number of participants in the analysis population for this outcome measure. Number Analyzed represents the number of participants with concentration measurement above lower limit of quantification at each visit. Group A was not evaluable for this outcome measure.
Arm/Group Title Group B: Avelumab + Lorlatinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 25
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ug/mL
Cycle 2 Day 1 Number Analyzed 22 participants
16.86
(88%)
Cycle 3 Day 1 Number Analyzed 19 participants
16.99
(116%)
Cycle 4 Day 1 Number Analyzed 21 participants
23.71
(80%)
Cycle 5 Day 1 Number Analyzed 16 participants
26.74
(68%)
Cycle 11 Day 1 Number Analyzed 15 participants
31.31
(71%)
Cycle 17 Day 1 Number Analyzed 13 participants
32.69
(60%)
Cycle 23 Day 1 Number Analyzed 11 participants
33.20
(56%)
Cycle 29 Day 1 Number Analyzed 10 participants
25.77
(66%)
Cycle 35 Day 1 Number Analyzed 10 participants
31.27
(47%)
Cycle 41 Day 1 Number Analyzed 7 participants
30.81
(59%)
Cycle 47 Day 1 Number Analyzed 8 participants
39.63
(64%)
30.Secondary Outcome
Title Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status
Hide Description ADA never-positive was defined as no positive ADA results at any time point. ADA ever-positive was defined as at least one positive ADA result at any time point. Baseline is defined as the last assessment on or prior to the date/time of the first dose of avelumab.
Time Frame Day 1 of Cycles 1-5, then every 12 weeks thereafter, end of treatment/withdrawal, and 30 days after last avelumab dose (up to a maximum of 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was a subset of the safety analysis set (all participants who received at least one dose of study drug) and included participants who had at least one ADA sample collected for avelumab.
Arm/Group Title Group A: Avelumab + Crizotinib Group B: Avelumab + Lorlatinib All Participants
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Including all the participants from Group A and Group B.
Overall Number of Participants Analyzed 12 31 43
Measure Type: Count of Participants
Unit of Measure: Participants
ADA never-positive
9
  75.0%
25
  80.6%
34
  79.1%
ADA ever-positive
3
  25.0%
6
  19.4%
9
  20.9%
31.Secondary Outcome
Title Number of Participants With Positive Programmed Death Ligand-1 (PD-L1) Biomarker Expression
Hide Description PD-L1 protein expression is determined by using Combined Positive Score (CPS), which is the percentage of viable tumor and tumor-infiltrated immune cells (restricted to lymphocytes and macrophages) within or directly associated with tumor cell strands showing partial or complete membrane staining using the SP263 antibody. Positive is defined as CPS>=1% and negative is defined as CPS <1%.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was a subset of the safety analysis set (all participants who received at least one dose of study drug) and included participants who had at least one biomarker parameter of PD-L1 from the corresponding assay sample with at least one baseline biomarker measurement.
Arm/Group Title Group A: Avelumab + Crizotinib Group B: Avelumab + Lorlatinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 9 24
Measure Type: Count of Participants
Unit of Measure: Participants
Positive
7
  77.8%
20
  83.3%
Negative
2
  22.2%
4
  16.7%
32.Secondary Outcome
Title Number of Participants With Positive Tumor Infiltrating CD8+ Lymphocytes
Hide Description Tumor infiltrating CD8+ lymphocytes is defined as the number of CD8+ cells per unit area and the percent of counted cells. Positive is defined as >=1% and negative is defined as <1%.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was a subset of the safety analysis set (all participants who received at least one dose of study drug) and included participants who had at least one biomarker parameter of tumor infiltrating CD8+ lymphocytes from the corresponding assay sample with at least one baseline biomarker measurement.
Arm/Group Title Group A: Avelumab + Crizotinib Group B: Avelumab + Lorlatinib
Hide Arm/Group Description:
Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule.
Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
Overall Number of Participants Analyzed 10 22
Measure Type: Count of Participants
Unit of Measure: Participants
Positive
6
  60.0%
4
  18.2%
Negative
4
  40.0%
18
  81.8%
Time Frame Baseline up to 30 days post lost dose of study treatment with a maximum of 5 years
Adverse Event Reporting Description The same event may appear as both an AE and an SAE. An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
 
Arm/Group Title Group A: Avelumab + Crizotinib Group B: Avelumab + Lorlatinib
Hide Arm/Group Description Participants with locally advanced or metastatic Anaplastic Lymphoma Kinase (ALK)-negative non-small cell lung cancer (NSCLC) received avelumab 10 mg/kg as a 1-hour intravenous (IV) infusion once every 2 weeks (Day 1 of each cycle) and crizotinib 250 mg (starting dose) orally twice a day (BID) on a continuous daily dosing schedule. Participants with locally advanced or metastatic ALK-positive NSCLC received avelumab 10 mg/kg as a 1-hour IV infusion once every 2 weeks (Day 1 of each cycle) and lorlatinib 100 mg (starting dose) orally once a day (QD) on a continuous daily dosing schedule.
All-Cause Mortality
Group A: Avelumab + Crizotinib Group B: Avelumab + Lorlatinib
Affected / at Risk (%) Affected / at Risk (%)
Total   10/12 (83.33%)   15/31 (48.39%) 
Hide Serious Adverse Events
Group A: Avelumab + Crizotinib Group B: Avelumab + Lorlatinib
Affected / at Risk (%) Affected / at Risk (%)
Total   5/12 (41.67%)   21/31 (67.74%) 
Blood and lymphatic system disorders     
Febrile neutropenia * 1  1/12 (8.33%)  0/31 (0.00%) 
Cardiac disorders     
Cardiac tamponade * 1  0/12 (0.00%)  1/31 (3.23%) 
Pericardial effusion * 1  0/12 (0.00%)  1/31 (3.23%) 
Gastrointestinal disorders     
Abdominal pain * 1  0/12 (0.00%)  1/31 (3.23%) 
General disorders     
Chest pain * 1  0/12 (0.00%)  1/31 (3.23%) 
Disease progression * 1  1/12 (8.33%)  0/31 (0.00%) 
Pyrexia * 1  0/12 (0.00%)  1/31 (3.23%) 
Sudden death * 1  0/12 (0.00%)  1/31 (3.23%) 
Hepatobiliary disorders     
Immune-mediated hepatitis * 1  1/12 (8.33%)  0/31 (0.00%) 
Infections and infestations     
Cellulitis * 1  0/12 (0.00%)  1/31 (3.23%) 
Clostridium difficile infection * 1  0/12 (0.00%)  1/31 (3.23%) 
Pneumonia * 1  0/12 (0.00%)  3/31 (9.68%) 
Postoperative wound infection * 1  0/12 (0.00%)  1/31 (3.23%) 
Sepsis * 1  0/12 (0.00%)  1/31 (3.23%) 
Tonsillitis * 1  0/12 (0.00%)  1/31 (3.23%) 
Injury, poisoning and procedural complications     
Femoral neck fracture * 1  0/12 (0.00%)  1/31 (3.23%) 
Femur fracture * 1  0/12 (0.00%)  1/31 (3.23%) 
Road traffic accident * 1  0/12 (0.00%)  1/31 (3.23%) 
Investigations     
Aspartate aminotransferase increased * 1  0/12 (0.00%)  1/31 (3.23%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Non-small cell lung cancer * 1  0/12 (0.00%)  1/31 (3.23%) 
Tongue neoplasm malignant stage unspecified * 1  0/12 (0.00%)  1/31 (3.23%) 
Nervous system disorders     
Central nervous system vasculitis * 1  0/12 (0.00%)  1/31 (3.23%) 
Cerebral haemorrhage * 1  0/12 (0.00%)  1/31 (3.23%) 
Cerebral infarction * 1  0/12 (0.00%)  1/31 (3.23%) 
Seizure * 1  0/12 (0.00%)  1/31 (3.23%) 
Psychiatric disorders     
Confusional state * 1  0/12 (0.00%)  2/31 (6.45%) 
Delirium * 1  0/12 (0.00%)  1/31 (3.23%) 
Renal and urinary disorders     
Nephrolithiasis * 1  0/12 (0.00%)  1/31 (3.23%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 1  0/12 (0.00%)  1/31 (3.23%) 
Pneumonitis * 1  1/12 (8.33%)  2/31 (6.45%) 
Pneumothorax * 1  1/12 (8.33%)  0/31 (0.00%) 
Pulmonary embolism * 1  0/12 (0.00%)  2/31 (6.45%) 
Skin and subcutaneous tissue disorders     
Rash * 1  1/12 (8.33%)  0/31 (0.00%) 
Vascular disorders     
Deep vein thrombosis * 1  0/12 (0.00%)  1/31 (3.23%) 
Superior vena cava occlusion * 1  0/12 (0.00%)  1/31 (3.23%) 
1
Term from vocabulary, MedDRA v25.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Group A: Avelumab + Crizotinib Group B: Avelumab + Lorlatinib
Affected / at Risk (%) Affected / at Risk (%)
Total   12/12 (100.00%)   28/31 (90.32%) 
Blood and lymphatic system disorders     
Anaemia * 1  3/12 (25.00%)  6/31 (19.35%) 
Thrombocytopenia * 1  1/12 (8.33%)  0/31 (0.00%) 
Cardiac disorders     
Atrioventricular block first degree * 1  0/12 (0.00%)  2/31 (6.45%) 
Pericardial effusion * 1  1/12 (8.33%)  1/31 (3.23%) 
Ear and labyrinth disorders     
Tinnitus * 1  1/12 (8.33%)  1/31 (3.23%) 
Endocrine disorders     
Hypothyroidism * 1  0/12 (0.00%)  8/31 (25.81%) 
Eye disorders     
Dry eye * 1  1/12 (8.33%)  1/31 (3.23%) 
Keratitis * 1  1/12 (8.33%)  0/31 (0.00%) 
Gastrointestinal disorders     
Abdominal discomfort * 1  1/12 (8.33%)  2/31 (6.45%) 
Abdominal pain * 1  1/12 (8.33%)  5/31 (16.13%) 
Constipation * 1  2/12 (16.67%)  7/31 (22.58%) 
Diarrhoea * 1  3/12 (25.00%)  7/31 (22.58%) 
Dry mouth * 1  1/12 (8.33%)  0/31 (0.00%) 
Gastrooesophageal reflux disease * 1  0/12 (0.00%)  2/31 (6.45%) 
Nausea * 1  7/12 (58.33%)  5/31 (16.13%) 
Oesophageal pain * 1  1/12 (8.33%)  0/31 (0.00%) 
Stomatitis * 1  1/12 (8.33%)  3/31 (9.68%) 
Vomiting * 1  6/12 (50.00%)  6/31 (19.35%) 
Abdominal distension * 1  0/12 (0.00%)  2/31 (6.45%) 
Proctalgia * 1  0/12 (0.00%)  2/31 (6.45%) 
General disorders     
Asthenia * 1  2/12 (16.67%)  3/31 (9.68%) 
Chest pain * 1  0/12 (0.00%)  4/31 (12.90%) 
Chills * 1  3/12 (25.00%)  2/31 (6.45%) 
Fatigue * 1  1/12 (8.33%)  4/31 (12.90%) 
Hypothermia * 1  1/12 (8.33%)  0/31 (0.00%) 
Localised oedema * 1  0/12 (0.00%)  2/31 (6.45%) 
Mucosal inflammation * 1  2/12 (16.67%)  0/31 (0.00%) 
Oedema * 1  1/12 (8.33%)  1/31 (3.23%) 
Oedema peripheral * 1  1/12 (8.33%)  12/31 (38.71%) 
Peripheral swelling * 1  0/12 (0.00%)  2/31 (6.45%) 
Pyrexia * 1  3/12 (25.00%)  5/31 (16.13%) 
Swelling face * 1  1/12 (8.33%)  1/31 (3.23%) 
Hepatobiliary disorders     
Immune-mediated hepatitis * 1  1/12 (8.33%)  0/31 (0.00%) 
Infections and infestations     
Cellulitis * 1  1/12 (8.33%)  3/31 (9.68%) 
Conjunctivitis * 1  0/12 (0.00%)  2/31 (6.45%) 
Cystitis * 1  0/12 (0.00%)  2/31 (6.45%) 
Gastroenteritis * 1  1/12 (8.33%)  1/31 (3.23%) 
Lower respiratory tract infection * 1  0/12 (0.00%)  2/31 (6.45%) 
Nasopharyngitis * 1  0/12 (0.00%)  3/31 (9.68%) 
Rhinitis * 1  0/12 (0.00%)  2/31 (6.45%) 
Tooth abscess * 1  0/12 (0.00%)  2/31 (6.45%) 
Upper respiratory tract infection * 1  1/12 (8.33%)  5/31 (16.13%) 
Urinary tract infection * 1  0/12 (0.00%)  3/31 (9.68%) 
Injury, poisoning and procedural complications     
Infusion related reaction * 1  2/12 (16.67%)  6/31 (19.35%) 
Procedural pain * 1  1/12 (8.33%)  2/31 (6.45%) 
Fall * 1  0/12 (0.00%)  2/31 (6.45%) 
Investigations     
Alanine aminotransferase increased * 1  4/12 (33.33%)  9/31 (29.03%) 
Amylase increased * 1  1/12 (8.33%)  3/31 (9.68%) 
Aspartate aminotransferase increased * 1  3/12 (25.00%)  7/31 (22.58%) 
Blood alkaline phosphatase increased * 1  1/12 (8.33%)  2/31 (6.45%) 
Blood cholesterol increased * 1  0/12 (0.00%)  19/31 (61.29%) 
Blood creatine phosphokinase increased * 1  1/12 (8.33%)  4/31 (12.90%) 
Blood creatinine increased * 1  2/12 (16.67%)  0/31 (0.00%) 
Blood lactate dehydrogenase increased * 1  1/12 (8.33%)  0/31 (0.00%) 
Electrocardiogram QT prolonged * 1  1/12 (8.33%)  0/31 (0.00%) 
Gamma-glutamyltransferase increased * 1  1/12 (8.33%)  3/31 (9.68%) 
Hypophonesis * 1  1/12 (8.33%)  0/31 (0.00%) 
Lipase increased * 1  1/12 (8.33%)  5/31 (16.13%) 
Neutrophil count decreased * 1  1/12 (8.33%)  0/31 (0.00%) 
Weight decreased * 1  1/12 (8.33%)  1/31 (3.23%) 
Weight increased * 1  0/12 (0.00%)  8/31 (25.81%) 
White blood cell count decreased * 1  1/12 (8.33%)  0/31 (0.00%) 
Blood triglycerides increased * 1  0/12 (0.00%)  2/31 (6.45%) 
Metabolism and nutrition disorders     
Acidosis * 1  1/12 (8.33%)  0/31 (0.00%) 
Decreased appetite * 1  5/12 (41.67%)  2/31 (6.45%) 
Hypercholesterolaemia * 1  0/12 (0.00%)  6/31 (19.35%) 
Hyperglycaemia * 1  0/12 (0.00%)  2/31 (6.45%) 
Hypertriglyceridaemia * 1  0/12 (0.00%)  18/31 (58.06%) 
Hypoalbuminaemia * 1  1/12 (8.33%)  2/31 (6.45%) 
Hypocalcaemia * 1  1/12 (8.33%)  1/31 (3.23%) 
Hypoglycaemia * 1  1/12 (8.33%)  1/31 (3.23%) 
Hypokalaemia * 1  0/12 (0.00%)  2/31 (6.45%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  0/12 (0.00%)  13/31 (41.94%) 
Back pain * 1  0/12 (0.00%)  4/31 (12.90%) 
Groin pain * 1  0/12 (0.00%)  2/31 (6.45%) 
Joint swelling * 1  0/12 (0.00%)  2/31 (6.45%) 
Muscle spasms * 1  0/12 (0.00%)  4/31 (12.90%) 
Muscular weakness * 1  0/12 (0.00%)  3/31 (9.68%) 
Musculoskeletal pain * 1  0/12 (0.00%)  2/31 (6.45%) 
Myalgia * 1  3/12 (25.00%)  6/31 (19.35%) 
Pain in extremity * 1  0/12 (0.00%)  4/31 (12.90%) 
Nervous system disorders     
Carpal tunnel syndrome * 1  0/12 (0.00%)  2/31 (6.45%) 
Dizziness * 1  1/12 (8.33%)  4/31 (12.90%) 
Dysgeusia * 1  0/12 (0.00%)  2/31 (6.45%) 
Headache * 1  1/12 (8.33%)  4/31 (12.90%) 
Hemiparesis * 1  1/12 (8.33%)  1/31 (3.23%) 
Lethargy * 1  0/12 (0.00%)  3/31 (9.68%) 
Memory impairment * 1  0/12 (0.00%)  3/31 (9.68%) 
Migraine * 1  1/12 (8.33%)  0/31 (0.00%) 
Neuropathy peripheral * 1  0/12 (0.00%)  7/31 (22.58%) 
Paraesthesia * 1  0/12 (0.00%)  2/31 (6.45%) 
Peripheral sensory neuropathy * 1  0/12 (0.00%)  5/31 (16.13%) 
Somnolence * 1  1/12 (8.33%)  1/31 (3.23%) 
Hyperaesthesia * 1  0/12 (0.00%)  2/31 (6.45%) 
Psychiatric disorders     
Confusional state * 1  0/12 (0.00%)  2/31 (6.45%) 
Hallucination * 1  0/12 (0.00%)  2/31 (6.45%) 
Hallucination, visual * 1  0/12 (0.00%)  2/31 (6.45%) 
Insomnia * 1  0/12 (0.00%)  6/31 (19.35%) 
Restlessness * 1  0/12 (0.00%)  2/31 (6.45%) 
Renal and urinary disorders     
Haematuria * 1  0/12 (0.00%)  2/31 (6.45%) 
Nephropathy toxic * 1  1/12 (8.33%)  0/31 (0.00%) 
Proteinuria * 1  0/12 (0.00%)  3/31 (9.68%) 
Reproductive system and breast disorders     
Vaginal discharge * 1  1/12 (8.33%)  0/31 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  1/12 (8.33%)  7/31 (22.58%) 
Dyspnoea * 1  2/12 (16.67%)  5/31 (16.13%) 
Dyspnoea exertional * 1  0/12 (0.00%)  2/31 (6.45%) 
Haemoptysis * 1  0/12 (0.00%)  4/31 (12.90%) 
Lung opacity * 1  1/12 (8.33%)  0/31 (0.00%) 
Nasal congestion * 1  0/12 (0.00%)  4/31 (12.90%) 
Oropharyngeal pain * 1  0/12 (0.00%)  2/31 (6.45%) 
Pneumonitis * 1  0/12 (0.00%)  2/31 (6.45%) 
Productive cough * 1  1/12 (8.33%)  0/31 (0.00%) 
Skin and subcutaneous tissue disorders     
Dry skin * 1  1/12 (8.33%)  4/31 (12.90%) 
Pruritus * 1  1/12 (8.33%)  2/31 (6.45%) 
Rash * 1  4/12 (33.33%)  5/31 (16.13%) 
Skin hypertrophy * 1  0/12 (0.00%)  2/31 (6.45%) 
Skin disorder * 1  0/12 (0.00%)  2/31 (6.45%) 
1
Term from vocabulary, MedDRA v25.0
*
Indicates events were collected by non-systematic assessment
Enrollment in the study was terminated early based on the changing landscape in treatment options for treatment naïve ALK positive NSCLC. This decision was not due to any safety concerns or regulatory interactions. All participants on active treatment at the time of the early enrollment termination could continue treatment and follow up per the protocol.
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
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02584634    
Other Study ID Numbers: B9991005
2015-001879-43 ( EudraCT Number )
JAVELIN LUNG 101 ( Other Identifier: Alias Study Number )
First Submitted: October 21, 2015
First Posted: October 22, 2015
Results First Submitted: January 13, 2022
Results First Posted: February 9, 2022
Last Update Posted: July 7, 2023