A Phase Ib/II Study of LEE011 in Combination With MEK162 in Patients With NRAS Mutant Melanoma
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ClinicalTrials.gov Identifier: NCT01781572 |
Recruitment Status :
Completed
First Posted : February 1, 2013
Results First Posted : August 12, 2020
Last Update Posted : December 7, 2020
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Study Type | Interventional |
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Study Design | Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment |
Condition |
Locally Advanced or Metastatic NRAS Mutant Melanoma |
Interventions |
Drug: LEE011 Drug: MEK162 |
Enrollment | 102 |
Recruitment Details | Upon study entry, all patients were required to provide either an archival tumor biopsy with the corresponding pathology report or a newly obtained tumor biopsy. Both parts of the study were limited to patients aged 18 or older with metastatic or locally advanced NRAS-mutant melanoma. |
Pre-assignment Details |
Screening details: Screening assessments were performed within 14 days prior to the first dose of ribociclib and binimetinib except for the pretreatment tumor biopsy, which was performed within 28 days before dosing. A total of 23 patients were screened but not enrolled. |
Arm/Group Title | Phase 1b 28-Day Schedule | Phase 1b 21-Day Schedule | Phase 2 (Dose-expansion Phase) |
---|---|---|---|
Arm/Group Description |
A combined total of 61 patients were treated in the 28-day (n=29) and 21-day (n=32) treatment cycles, and all patients discontinued treatment. The starting dose in the 28-day schedule was binimetinib 45 mg BID + ribociclib 200 mg QD. 28-Day Schedule: ribociclib was taken QD for 21 consecutive days followed by a 7-day planned break. Binimetinib was taken BID on a continuous dosing schedule. |
A combined total of 61 patients were treated in the 28-day (n=29) and 21-day (n=32) treatment cycles, and all patients discontinued treatment. The starting dose in the 21-day schedule was binimetinib 30 mg BID + ribociclib 200 mg QD. 21-Day Schedule: ribociclib QD and binimetinib BID were taken QD for 14 consecutive days followed by a 7-day planned break. |
The dose-expansion phase was initiated with a newly recruited group of patients. A total of 41 patients were treated, and all patients (100%) discontinued treatment. Based on the recommendations of the dose-escalation meetings between the Sponsor and the Investigators, the RP2D and schedule for the combination of binimetinib and ribociclib to be used for the dose-expansion phase of the study was binimetinib 45 mg BID + ribociclib 200 mg QD on the 28-day schedule. |
Period Title: MEK162 45mg BID+LEE011 200mg | |||
Started | 16 | 6 | 41 |
Completed | 0 | 0 | 0 |
Not Completed | 16 | 6 | 41 |
Reason Not Completed | |||
Adverse Event | 7 | 0 | 11 |
Progressive disease | 8 | 6 | 23 |
Withdrawal by Subject | 1 | 0 | 2 |
Physician Decision | 0 | 0 | 4 |
Death | 0 | 0 | 1 |
Period Title: MEK162 45mg BID+LEE011 250mg | |||
Started | 3 | 0 | 0 |
Completed | 0 | 0 | 0 |
Not Completed | 3 | 0 | 0 |
Reason Not Completed | |||
Progressive Disease | 2 | 0 | 0 |
Withdrawal by Subject | 1 | 0 | 0 |
Period Title: MEK162 30mg BID+LEE011 300mg | |||
Started | 4 | 2 | 0 |
Completed | 0 | 0 | 0 |
Not Completed | 4 | 2 | 0 |
Reason Not Completed | |||
Adverse Event | 1 | 0 | 0 |
Progressive Disease | 3 | 2 | 0 |
Period Title: MEK162 45mg BID+LEE011 300mg | |||
Started | 6 | 4 | 0 |
Completed | 0 | 0 | 0 |
Not Completed | 6 | 4 | 0 |
Reason Not Completed | |||
Adverse Event | 1 | 1 | 0 |
Progressive Disease | 4 | 3 | 0 |
Death | 1 | 0 | 0 |
Period Title: MEK162 30mg LEE011 200mg | |||
Started | 0 | 5 | 0 |
Completed | 0 | 0 | 0 |
Not Completed | 0 | 5 | 0 |
Reason Not Completed | |||
Progressive Disease | 0 | 5 | 0 |
Period Title: MEK162 45mg LEE011 450mg | |||
Started | 0 | 9 | 0 |
Completed | 0 | 0 | 0 |
Not Completed | 0 | 9 | 0 |
Reason Not Completed | |||
Adverse Event | 0 | 1 | 0 |
Physician Decision | 0 | 2 | 0 |
Progressive Disease | 0 | 6 | 0 |
Period Title: MEK162 45mg LEE011 600mg | |||
Started | 0 | 6 | 0 |
Completed | 0 | 0 | 0 |
Not Completed | 0 | 6 | 0 |
Reason Not Completed | |||
Adverse Event | 0 | 1 | 0 |
Progressive Disease | 0 | 5 | 0 |
Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | Phase 2: MEK162 45mg+LEE011 200mg | Total | |
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Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 200mg | Total of all reporting groups | |
Overall Number of Baseline Participants | 16 | 3 | 4 | 6 | 5 | 6 | 2 | 4 | 9 | 6 | 41 | 102 | |
Baseline Analysis Population Description |
The baseline analysis population consists of the Full Analysis Set (FAS), which includes all patients who received at least 1 dose of ribociclib or binimetinib.
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Age, Categorical
Measure Type: Count of Participants Unit of measure: Participants |
|||||||||||||
Number Analyzed | 16 participants | 3 participants | 4 participants | 6 participants | 5 participants | 6 participants | 2 participants | 4 participants | 9 participants | 6 participants | 41 participants | 102 participants | |
<=18 years |
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
|
Between 18 and 65 years |
9 56.3%
|
2 66.7%
|
2 50.0%
|
4 66.7%
|
3 60.0%
|
3 50.0%
|
1 50.0%
|
2 50.0%
|
4 44.4%
|
5 83.3%
|
19 46.3%
|
54 52.9%
|
|
>=65 years |
7 43.8%
|
1 33.3%
|
2 50.0%
|
2 33.3%
|
2 40.0%
|
3 50.0%
|
1 50.0%
|
2 50.0%
|
5 55.6%
|
1 16.7%
|
22 53.7%
|
48 47.1%
|
|
Age, Continuous
Median (Standard Deviation) Unit of measure: Years |
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Number Analyzed | 16 participants | 3 participants | 4 participants | 6 participants | 5 participants | 6 participants | 2 participants | 4 participants | 9 participants | 6 participants | 41 participants | 102 participants | |
62 (14.51) | 57 (9.02) | 61.5 (21.30) | 56 (15.04) | 63.0 (7.50) | 62.5 (12.687) | 55.0 (18.38) | 63.5 (19.48) | 67.0 (8.59) | 58.5 (5.56) | 65 (12.35) | 61 (12.72) | ||
Sex: Female, Male
Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 16 participants | 3 participants | 4 participants | 6 participants | 5 participants | 6 participants | 2 participants | 4 participants | 9 participants | 6 participants | 41 participants | 102 participants | |
Female |
8 50.0%
|
0 0.0%
|
3 75.0%
|
1 16.7%
|
2 40.0%
|
3 50.0%
|
1 50.0%
|
2 50.0%
|
1 11.1%
|
5 83.3%
|
15 36.6%
|
41 40.2%
|
|
Male |
8 50.0%
|
3 100.0%
|
1 25.0%
|
5 83.3%
|
3 60.0%
|
3 50.0%
|
1 50.0%
|
2 50.0%
|
8 88.9%
|
1 16.7%
|
26 63.4%
|
61 59.8%
|
|
Race/Ethnicity, Customized
Measure Type: Count of Participants Unit of measure: Participants |
|||||||||||||
Race | Number Analyzed | 16 participants | 3 participants | 4 participants | 6 participants | 5 participants | 6 participants | 2 participants | 4 participants | 9 participants | 6 participants | 41 participants | 102 participants |
Caucasian |
16 100.0%
|
3 100.0%
|
4 100.0%
|
6 100.0%
|
5 100.0%
|
6 100.0%
|
1 50.0%
|
4 100.0%
|
9 100.0%
|
6 100.0%
|
40 97.6%
|
100 98.0%
|
|
Other |
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
1 50.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
1 2.4%
|
2 2.0%
|
|
Weight
Mean (Standard Deviation) Unit of measure: Kilograms |
|||||||||||||
Number Analyzed | 16 participants | 3 participants | 4 participants | 6 participants | 5 participants | 6 participants | 2 participants | 4 participants | 9 participants | 6 participants | 41 participants | 102 participants | |
82.57 (15.014) | 91.47 (20.093) | 71.30 (12.631) | 97.48 (35.464) | 73.66 (8.104) | 85.20 (20.733) | 80.80 (15.274) | 97.20 (24.554) | 92.41 (20.709) | 62.95 (6.111) | 79.63 (17.334) | 83.69 (20.621) | ||
Body mass index
Mean (Standard Deviation) Unit of measure: (kg)/m^2 |
|||||||||||||
Number Analyzed | 16 participants | 3 participants | 4 participants | 6 participants | 5 participants | 6 participants | 2 participants | 4 participants | 9 participants | 6 participants | 41 participants | 102 participants | |
28.57 (5.136) | 26.84 (5.332) | 25.95 (3.347) | 30.38 (9.733) | 23.85 (2.451) | 27.80 (6.185) | 27.92 (7.526) | 31.71 (5.305) | 28.08 (6.594) | 23.50 (3.293) | 26.69 (5.014) | 27.34 (5.841) | ||
ECOG performance status
Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 16 participants | 3 participants | 4 participants | 6 participants | 5 participants | 6 participants | 2 participants | 4 participants | 9 participants | 6 participants | 41 participants | 102 participants | |
0-Without restriction |
10 62.5%
|
2 66.7%
|
1 25.0%
|
2 33.3%
|
3 60.0%
|
5 83.3%
|
2 100.0%
|
2 50.0%
|
5 55.6%
|
5 83.3%
|
28 68.3%
|
65 63.7%
|
|
1-Restricted in physically strenuous activity |
5 31.3%
|
0 0.0%
|
3 75.0%
|
4 66.7%
|
2 40.0%
|
1 16.7%
|
0 0.0%
|
2 50.0%
|
4 44.4%
|
1 16.7%
|
13 31.7%
|
35 34.3%
|
|
2-Ambulatory and capable of all selfcare |
1 6.3%
|
1 33.3%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
2 2.0%
|
Name/Title: | Study Director |
Organization: | Pfizer |
Phone: | 1-800-718-1021 |
EMail: | ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party: | Pfizer |
ClinicalTrials.gov Identifier: | NCT01781572 |
Other Study ID Numbers: |
CMEK162X2114 C4211005 ( Other Identifier: Pfizer ) |
First Submitted: | January 24, 2013 |
First Posted: | February 1, 2013 |
Results First Submitted: | May 6, 2020 |
Results First Posted: | August 12, 2020 |
Last Update Posted: | December 7, 2020 |