Phase Ib/II Study of Efficacy and Safety of MEK162 and Panitumumab, in Adult mCRC Patients With Mutant or Wild-type RAS Tumors
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT01927341
Collaborator
(none)
53
8
5
26.2
6.6
0.3
Study Details
Study Description
Brief Summary
The primary purpose of the phase Ib is to estimate the MTD/RPD2 and of the phase II is to assess the anti-tumor activity of MEK162 in combination with panitumumab.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
53 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
A Phase Ib/II, Open-label, Multi-center, Dose Escalation Study of MEK162 in Combination With Panitumumab in Adult Patients With Mutant RAS or Wild-type RAS Metastatic Colorectal Cancer
Actual Study Start Date
:
Nov 19, 2013
Actual Primary Completion Date
:
Jan 25, 2016
Actual Study Completion Date
:
Jan 25, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase Ib: Dose escalation Phase Ib: Dose escalation. |
Drug: MEK162
Tablet for oral use, 45 mg (three 15 mg tablets), BID
Drug: Panitumumab
Intravenous infusion, 20mg/ml concentrate solution for infusion, Q2W (Days 1 and 15 of every cycle)
|
| Experimental: Phase II: Patients with mutant RAS mCRC Patients with mutant RAS mCRC who have not been pretreated with an EGFR inhibitor (EGFRi), including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy. |
Drug: MEK162
Tablet for oral use, 45 mg (three 15 mg tablets), BID
Drug: Panitumumab
Intravenous infusion, 20mg/ml concentrate solution for infusion, Q2W (Days 1 and 15 of every cycle)
|
| Experimental: Phase II: Patients with acquired mutant RAS mCRC Patients with acquired mutant RAS mCRC who have been pretreated with anti-EGFR monoclonal antibody therapy, but have not been pre-treated with EGFR tyrosine kinase inhibitor therapy. |
Drug: MEK162
Tablet for oral use, 45 mg (three 15 mg tablets), BID
Drug: Panitumumab
Intravenous infusion, 20mg/ml concentrate solution for infusion, Q2W (Days 1 and 15 of every cycle)
|
| Experimental: Phase II: Patients with WT RAS mCRC (pretreated) Patients with WT RAS mCRC who have been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy. |
Drug: MEK162
Tablet for oral use, 45 mg (three 15 mg tablets), BID
Drug: Panitumumab
Intravenous infusion, 20mg/ml concentrate solution for infusion, Q2W (Days 1 and 15 of every cycle)
|
| Experimental: Phase II: Patients with WT RAS mCRC (not pretreated) Patients with WT RAS mCRC who have not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy. |
Drug: MEK162
Tablet for oral use, 45 mg (three 15 mg tablets), BID
Drug: Panitumumab
Intravenous infusion, 20mg/ml concentrate solution for infusion, Q2W (Days 1 and 15 of every cycle)
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Dose-limiting Toxicities (DLT): Phase 1b [Within the first 28 days of treatment with binimetinib and panitumumab (Cycle 1)]
DLT was defined as an adverse event or clinically significant abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first 28 days of treatment (Cycle 1) with binimetinib and panitumumab and met any of the specified criteria.
- Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 2 [From the start of the treatment until CR or PR (approximately up to 11 months)]
ORR: percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) as assessed per RECIST version 1.1. BOR: the best response recorded from the start of the treatment until CR or PR. 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 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Secondary Outcome Measures
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) [Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months)]
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
- Number of Participants With Vital Sign Abnormalities [Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months)]
Vital sign abnormalities criteria included: 1) Systolic blood pressure (SBP) in millimeters of mercury (mmHg): greater than or equal to (>=)180 mmHg or less than equal to (<=) 90 mmHg with increase or decrease from baseline of >=20 mmHg with high and low post baseline values; 2) Diastolic blood pressure (DBP) (mmHg): >=105 mmHg or <=50 mmHg with increase or decrease from baseline of >=15 mmHg with high and low post baseline values; 3) Pulse rate in beats per minutes (bpm): >=120 bpm or <=50 bpm with increase or decrease from baseline of >=15 bpm with high and low post baseline values; 4) Weight in kilogram: >=10% increase or decrease from baseline with high and low post baseline values; 5) Oral body temperature in degree Celsius (C) : >=39 degree C or <=35 degree C with high and low post baseline values. Categories, with at least 1 participant having vital sign abnormality in any of the reporting arms, were reported in this outcome measure.
- Number of Participants With Electrocardiogram (ECG) Abnormalities [Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months)]
ECG abnormalities criteria included: 1) QTc interval adjusted according to Bazett formula (QTcB) in millisecond (msec): greater than (>) 450, >480, >500, increase from baseline >30, increase from baseline >60; 2) QTc interval adjusted according to Fridericia formula (QTcF) (msec): >450, >480, >500, increase from baseline >30, increase from baseline >60; 3) Heart rate (bpm): RR decrease >25% and to a VR (interval between QRS wave and T wave on ECG) >100; RR (interval between 2 successive R waves on ECG) increase >25% and to a VR <50; 4) Pulse rate (msec): increase >25% and to a value >200; 5) QT (msec): >450, >480, >500, increase from baseline >30, increase from baseline >60; 6) QRS (msec): increase >25% and to a value >110. Categories, with at least 1 participant having ECG abnormality in any of the reporting arms, were reported in this outcome measure.
- Number of Participants With Clinically Significant Laboratory Abnormalities [Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months)]
Following parameters were analyzed for laboratory examination: hematology (hematocrit, erythrocytes); biochemistry (direct bilirubin, blood urea nitrogen, calcium, creatine kinase, triiodothyronine, thyroxine and thyrotropin). Clinical significance of laboratory abnormalities were judged by investigator.
- Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 1b [From the start of the treatment until disease progression (approximately up to 11 months)]
ORR: percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) as assessed per RECIST version 1.1. BOR: the best response recorded from the start of the treatment until CR or PR. 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 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
- Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment [From the date of randomization to the date of the first documented PD or death (approximately up to 11 months)]
PFS: time from date of randomization to date of first documented PD or death due to any cause, whichever occurred first. RECIST 1.1, PD:>=20% increase in sum of diameter of all measured target lesions (TLs), taking as reference smallest sum of diameter of all TLs recorded at or after baseline, sum must also be absolute increase of >=5 mm^2. Unequivocal progression of existing non-TLs. Appearance of new lesions. With no event at time of analysis cut-off or at start of any new anti-neoplastic therapy, PFS was censored at date of last adequate tumor assessment of complete response (CR), partial response (PR) or stable disease (SD). CR:disappearance of all non-nodal TLs/non TLs, any pathological lymph nodes as TLs/non TLs must have reduction in short axis to <10 mm. PR:>=30% decrease in sum of diameter of all TLs, referring baseline sum of diameters. SD:neither sufficient shrinkage to qualify for PR or CR nor increase in lesions qualified for PD. Kaplan-Meier method used for PFS analysis.
- Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment [From the first documented occurrence of response (PR or CR) until the date of the first documented PD or death due to the underlying cancer (approximately up to 11 months)]
DOR: time from first documented occurrence of response (PR or CR) until date of first documented PD or death due to underlying cancer. RECIST 1.1. 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. 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^2. Unequivocal progression of existing non-target lesions. Appearance of new lesions. Participants with no PD and were still alive, were censored at last adequate tumor assessment. Kaplan-Meier method was used for DOR analysis.
- Disease Control Rate (DCR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment [From the start of the treatment until disease progression (approximately up to 11 months)]
DCR was defined as the percentage of participants with a confirmed BOR of CR, PR, or stable disease (SD). RECIST 1.1, BOR was defined as the best response recorded from the start of the treatment until CR, PR or SD. 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 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. PD: at least a 20% increase in the 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%, the sum must also demonstrate an absolute increase of at least 5 mm^2. Unequivocal progression of existing non-target lesions. Appearance of new lesions.
- Overall Survival (OS) [From the start of treatment to the date of death due to any cause (approximately up to 11 months)]
OS was defined as the time from the start of treatment to the date of death due to any cause. If a participant was not known to have died, survival was censored at the date of last known date patient alive. Kaplan-Meier method was used for OS analysis.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Age ≥ 18 years
-
Metastatic colorectal cancer
-
Progression on or following standard therapy, or no standard therapy (phase Ib). Progression on or following at least 2-prior fluoropyrimidine-containing chemotherapy regimens (phase II)
-
Written documentation of mutant or wild-type RAS
-
Life expectancy ≥ 3 months
-
ECOG performance status ≤ 2
Exclusion Criteria:
Phase II arms 1 and 4 only: previous treatment with cetuximab, panitumumab, and/or other EGFR inhibitors
-
Previous treatment with MEK-inhibitors
-
History of severe infusion reactions to monoclonal antibodies.
-
Symptomatic or untreated leptomeningeal disease
-
Symptomatic brain metastasis
-
Current evidence of retinal disease; history of CSR, RVO or ophthalmopathy as assessed by ophthalmologic examination at baseline that would be considered a risk factor for CSR/RVO and history of keratitis.
-
Acute or chronic pancreatitis
-
Clinically significant cardiac disease
-
Not adequate hematologic, renal and hepatic function
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California at Los Angeles Dept of Onc | Los Angeles | California | United States | 90095 |
| 2 | Memorial Sloan Kettering Cancer Center Oncology Dept | New York | New York | United States | 90033 |
| 3 | Pfizer Investigative Site | Leuven | Belgium | 3000 | |
| 4 | Pfizer Investigative Site | Toronto | Ontario | Canada | M5G 2M9 |
| 5 | Pfizer Investigative Site | Toulouse Cedex 9 | France | 31059 | |
| 6 | Pfizer Investigative Site | Milano | MI | Italy | 20162 |
| 7 | Pfizer Investigative Site | Amsterdam | Netherlands | 1066 CX | |
| 8 | Pfizer Investigative Site | Barcelona | Catalunya | Spain | 08035 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01927341
Other Study ID Numbers:
- CMEK162X2116
- C4211008
- 2013-001986-18
First Posted:
Aug 22, 2013
Last Update Posted:
Feb 18, 2021
Last Verified:
Jan 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Study had Phase 1b followed by Phase 2. Phase 1b was to evaluate the maximum tolerated dose (MTD)/recommended Phase 2 dose (RPD2) in participants with mutant or wild type (WT) rat sarcoma viral oncogene homologue (RAS) metastatic colorectal cancer (mCRC) who had progressed on or following standard therapy or for whom no standard therapy existed. Phase 2 assessed anti-tumor activity in participants enrolled based on the previous anti-EGFR monoclonal antibody therapy and RAS mutational status. |
|---|---|
| Pre-assignment Detail | The study used binimetinib 45 mg twice a day (BID) and panitumumab 6 mg/kg intravenous infusion once every second week without planned dose escalation. |
| Arm/Group Title | Phase 1b: Binimetinib (MEK162) + Panitumumab | Phase 2:Mutant RAS Epidermal Growth Factor Receptor Inhibitor(EGFRi)-Naive:Binimetinib + Panitumumab | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received binimetinib 45 milligram (mg) orally twice daily with panitumumab 6 milligram per kilogram (mg/kg) intravenous (IV) infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 40 weeks. | Participants with mutant RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 15.4 weeks. | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. |
| Period Title: Phase 1b | |||||
| STARTED | 10 | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 10 | 0 | 0 | 0 | 0 |
| Period Title: Phase 1b | |||||
| STARTED | 0 | 15 | 5 | 15 | 8 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 15 | 5 | 15 | 8 |
Baseline Characteristics
| Arm/Group Title | Phase 1b: Binimetinib + Panitumumab | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 40 weeks. | Participants with mutant RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 15.4 weeks. | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. | Total of all reporting groups |
| Overall Participants | 10 | 15 | 5 | 15 | 8 | 53 |
| Age (Years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [Years] |
54.1
(10.6)
|
54.3
(11.2)
|
60.2
(12.0)
|
59.8
(14.0)
|
54.1
(10.7)
|
56.4
(11.8)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
4
40%
|
9
60%
|
4
80%
|
9
60%
|
5
62.5%
|
31
58.5%
|
| Male |
6
60%
|
6
40%
|
1
20%
|
6
40%
|
3
37.5%
|
22
41.5%
|
Outcome Measures
| Title | Number of Participants With Dose-limiting Toxicities (DLT): Phase 1b |
|---|---|
| Description | DLT was defined as an adverse event or clinically significant abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first 28 days of treatment (Cycle 1) with binimetinib and panitumumab and met any of the specified criteria. |
| Time Frame | Within the first 28 days of treatment with binimetinib and panitumumab (Cycle 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Dose determining set included all phase 1b participants who received at least 1 dose of binimetinib or panitumumab and had at least 1 valid post baseline safety assessment, and those who had either experienced a DLT at any time during Cycle 1 or had met the following minimum treatment and safety evaluation requirements without experiencing a DLT during Cycle 1. |
| Arm/Group Title | Phase 1b: Binimetinib + Panitumumab |
|---|---|
| Arm/Group Description | Participants received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 40 weeks. |
| Measure Participants | 10 |
| Count of Participants [Participants] |
0
0%
|
| Title | Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 2 |
|---|---|
| Description | ORR: percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) as assessed per RECIST version 1.1. BOR: the best response recorded from the start of the treatment until CR or PR. 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 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. |
| Time Frame | From the start of the treatment until CR or PR (approximately up to 11 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set included all participants who received at least 1 full or partial dose of study drug. |
| Arm/Group Title | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab |
|---|---|---|---|---|
| Arm/Group Description | Participants with mutant RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 15.4 weeks. | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. |
| Measure Participants | 15 | 5 | 15 | 8 |
| Number [Percentage of participants] |
0
0%
|
0
0%
|
6.7
134%
|
0
0%
|
| Title | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) |
|---|---|
| Description | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. |
| Time Frame | Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all participants who received at least 1 full or partial dose of study drug and had at least 1 valid post-baseline safety assessment. |
| Arm/Group Title | Phase 1b: Binimetinib + Panitumumab | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 40 weeks. | Participants with mutant RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 15.4 weeks. | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. |
| Measure Participants | 10 | 15 | 5 | 15 | 8 |
| TEAEs |
10
100%
|
15
100%
|
5
100%
|
15
100%
|
8
100%
|
| SAEs |
3
30%
|
6
40%
|
2
40%
|
9
60%
|
5
62.5%
|
| Title | Number of Participants With Vital Sign Abnormalities |
|---|---|
| Description | Vital sign abnormalities criteria included: 1) Systolic blood pressure (SBP) in millimeters of mercury (mmHg): greater than or equal to (>=)180 mmHg or less than equal to (<=) 90 mmHg with increase or decrease from baseline of >=20 mmHg with high and low post baseline values; 2) Diastolic blood pressure (DBP) (mmHg): >=105 mmHg or <=50 mmHg with increase or decrease from baseline of >=15 mmHg with high and low post baseline values; 3) Pulse rate in beats per minutes (bpm): >=120 bpm or <=50 bpm with increase or decrease from baseline of >=15 bpm with high and low post baseline values; 4) Weight in kilogram: >=10% increase or decrease from baseline with high and low post baseline values; 5) Oral body temperature in degree Celsius (C) : >=39 degree C or <=35 degree C with high and low post baseline values. Categories, with at least 1 participant having vital sign abnormality in any of the reporting arms, were reported in this outcome measure. |
| Time Frame | Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all participants who received at least 1 full or partial dose of study drug and had at least 1 valid post-baseline safety assessment. |
| Arm/Group Title | Phase 1b: Binimetinib + Panitumumab | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 40 weeks. | Participants with mutant RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 15.4 weeks. | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. |
| Measure Participants | 10 | 15 | 5 | 15 | 8 |
| SBP :>=180 mmHg or <=90 mmHg with increase or decrease from baseline of >=20 mmHg: low only |
0
0%
|
1
6.7%
|
1
20%
|
2
13.3%
|
0
0%
|
| DBP: >=105 mmHg or <=50 mmHg with increase or decrease from baseline of >=15 mmHg: high only |
0
0%
|
1
6.7%
|
0
0%
|
0
0%
|
0
0%
|
| Pulse: >=120 bpm or <=50 bpm with increase or decrease from baseline of >=15 bpm: high only |
0
0%
|
3
20%
|
1
20%
|
2
13.3%
|
1
12.5%
|
| Pulse:>=120 bpm or <=50 bpm with increase or decrease from baseline of >=15 bpm: low only |
0
0%
|
0
0%
|
0
0%
|
1
6.7%
|
0
0%
|
| Weight: >=10 % increase or decrease from baseline: high only |
0
0%
|
1
6.7%
|
0
0%
|
1
6.7%
|
0
0%
|
| Weight: >=10 % increase or decrease from baseline: low only |
1
10%
|
0
0%
|
0
0%
|
1
6.7%
|
0
0%
|
| Oral body temperature: >=39 °C or <=35 °C: high only |
1
10%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Oral body temperature: >=39 °C or <=35 °C: low only |
0
0%
|
0
0%
|
1
20%
|
0
0%
|
1
12.5%
|
| Title | Number of Participants With Electrocardiogram (ECG) Abnormalities |
|---|---|
| Description | ECG abnormalities criteria included: 1) QTc interval adjusted according to Bazett formula (QTcB) in millisecond (msec): greater than (>) 450, >480, >500, increase from baseline >30, increase from baseline >60; 2) QTc interval adjusted according to Fridericia formula (QTcF) (msec): >450, >480, >500, increase from baseline >30, increase from baseline >60; 3) Heart rate (bpm): RR decrease >25% and to a VR (interval between QRS wave and T wave on ECG) >100; RR (interval between 2 successive R waves on ECG) increase >25% and to a VR <50; 4) Pulse rate (msec): increase >25% and to a value >200; 5) QT (msec): >450, >480, >500, increase from baseline >30, increase from baseline >60; 6) QRS (msec): increase >25% and to a value >110. Categories, with at least 1 participant having ECG abnormality in any of the reporting arms, were reported in this outcome measure. |
| Time Frame | Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all participants who received at least 1 full or partial dose of study drug and had at least 1 valid post-baseline safety assessment. Here, "number analyzed" signifies participants evaluable at specific rows. |
| Arm/Group Title | Phase 1b: Binimetinib + Panitumumab | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 40 weeks. | Participants with mutant RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 15.4 weeks. | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. |
| Measure Participants | 10 | 15 | 5 | 15 | 8 |
| QTcB: >450 msec |
3
30%
|
2
13.3%
|
1
20%
|
5
33.3%
|
1
12.5%
|
| QTcB: >480 msec |
1
10%
|
1
6.7%
|
0
0%
|
2
13.3%
|
0
0%
|
| QTcB: >500 msec |
0
0%
|
1
6.7%
|
0
0%
|
0
0%
|
0
0%
|
| QTcB: Increase from baseline >30 msec |
3
30%
|
5
33.3%
|
1
20%
|
1
6.7%
|
2
25%
|
| QTcF: >450 msec |
1
10%
|
1
6.7%
|
0
0%
|
1
6.7%
|
2
25%
|
| QTcF: Increase from baseline >30 msec |
3
30%
|
2
13.3%
|
1
20%
|
1
6.7%
|
1
12.5%
|
| Heart rate: RR decrease >25% and to a VR >100 bpm |
1
10%
|
1
6.7%
|
0
0%
|
1
6.7%
|
0
0%
|
| Heart rate: RR increase >25% and to a VR <50 bpm |
0
0%
|
1
6.7%
|
0
0%
|
0
0%
|
0
0%
|
| QT: >450 msec |
0
0%
|
1
6.7%
|
0
0%
|
1
6.7%
|
1
12.5%
|
| QT: >480 msec |
0
0%
|
1
6.7%
|
0
0%
|
0
0%
|
0
0%
|
| QT: increase from baseline >30 msec |
6
60%
|
3
20%
|
1
20%
|
5
33.3%
|
4
50%
|
| QT: increase from baseline >60 msec |
0
0%
|
2
13.3%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Clinically Significant Laboratory Abnormalities |
|---|---|
| Description | Following parameters were analyzed for laboratory examination: hematology (hematocrit, erythrocytes); biochemistry (direct bilirubin, blood urea nitrogen, calcium, creatine kinase, triiodothyronine, thyroxine and thyrotropin). Clinical significance of laboratory abnormalities were judged by investigator. |
| Time Frame | Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all participants who received at least 1 full or partial dose of study drug and had at least 1 valid post-baseline safety assessment. |
| Arm/Group Title | Phase 1b: Binimetinib + Panitumumab | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 40 weeks. | Participants with mutant RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 15.4 weeks. | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. |
| Measure Participants | 10 | 15 | 5 | 15 | 8 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 1b |
|---|---|
| Description | ORR: percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) as assessed per RECIST version 1.1. BOR: the best response recorded from the start of the treatment until CR or PR. 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 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. |
| Time Frame | From the start of the treatment until disease progression (approximately up to 11 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set included all participants who received at least 1 full or partial dose of study drug. |
| Arm/Group Title | Phase 1b: Binimetinib + Panitumumab |
|---|---|
| Arm/Group Description | Participants received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 40 weeks. |
| Measure Participants | 10 |
| Number [Percentage of participants] |
0
0%
|
| Title | Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment |
|---|---|
| Description | PFS: time from date of randomization to date of first documented PD or death due to any cause, whichever occurred first. RECIST 1.1, PD:>=20% increase in sum of diameter of all measured target lesions (TLs), taking as reference smallest sum of diameter of all TLs recorded at or after baseline, sum must also be absolute increase of >=5 mm^2. Unequivocal progression of existing non-TLs. Appearance of new lesions. With no event at time of analysis cut-off or at start of any new anti-neoplastic therapy, PFS was censored at date of last adequate tumor assessment of complete response (CR), partial response (PR) or stable disease (SD). CR:disappearance of all non-nodal TLs/non TLs, any pathological lymph nodes as TLs/non TLs must have reduction in short axis to <10 mm. PR:>=30% decrease in sum of diameter of all TLs, referring baseline sum of diameters. SD:neither sufficient shrinkage to qualify for PR or CR nor increase in lesions qualified for PD. Kaplan-Meier method used for PFS analysis. |
| Time Frame | From the date of randomization to the date of the first documented PD or death (approximately up to 11 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set included all participants who received at least 1 full or partial dose of study drug. |
| Arm/Group Title | Phase 1b: Binimetinib + Panitumumab | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 40 weeks. | Participants with mutant RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 15.4 weeks. | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. |
| Measure Participants | 10 | 15 | 5 | 15 | 8 |
| Median (95% Confidence Interval) [Months] |
3.4
|
1.7
|
1.8
|
2.4
|
2.1
|
| Title | Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment |
|---|---|
| Description | DOR: time from first documented occurrence of response (PR or CR) until date of first documented PD or death due to underlying cancer. RECIST 1.1. 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. 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^2. Unequivocal progression of existing non-target lesions. Appearance of new lesions. Participants with no PD and were still alive, were censored at last adequate tumor assessment. Kaplan-Meier method was used for DOR analysis. |
| Time Frame | From the first documented occurrence of response (PR or CR) until the date of the first documented PD or death due to the underlying cancer (approximately up to 11 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set included all participants who received at least 1 full or partial dose of study drug. The outcome was to be analyzed only in confirmed responders, none of the reporting arms had confirmed responders except Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab. |
| Arm/Group Title | Phase 1b: Binimetinib + Panitumumab | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 40 weeks. | Participants with mutant RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 15.4 weeks. | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. |
| Measure Participants | 0 | 0 | 0 | 1 | 0 |
| Median (95% Confidence Interval) [Months] |
5.3
|
| Title | Disease Control Rate (DCR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment |
|---|---|
| Description | DCR was defined as the percentage of participants with a confirmed BOR of CR, PR, or stable disease (SD). RECIST 1.1, BOR was defined as the best response recorded from the start of the treatment until CR, PR or SD. 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 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. PD: at least a 20% increase in the 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%, the sum must also demonstrate an absolute increase of at least 5 mm^2. Unequivocal progression of existing non-target lesions. Appearance of new lesions. |
| Time Frame | From the start of the treatment until disease progression (approximately up to 11 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set included all participants who received at least 1 full or partial dose of study drug. |
| Arm/Group Title | Phase 1b: Binimetinib + Panitumumab | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 40 weeks. | Participants with mutant RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 15.4 weeks. | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. |
| Measure Participants | 10 | 15 | 5 | 15 | 8 |
| Number (95% Confidence Interval) [Percentage of participants] |
70.0
700%
|
13.3
88.7%
|
40.0
800%
|
40.0
266.7%
|
37.5
468.8%
|
| Title | Overall Survival (OS) |
|---|---|
| Description | OS was defined as the time from the start of treatment to the date of death due to any cause. If a participant was not known to have died, survival was censored at the date of last known date patient alive. Kaplan-Meier method was used for OS analysis. |
| Time Frame | From the start of treatment to the date of death due to any cause (approximately up to 11 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set included all participants who received at least 1 full or partial dose of study drug. |
| Arm/Group Title | Phase 1b: Binimetinib + Panitumumab | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 40 weeks. | Participants with mutant RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 15.4 weeks. | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. |
| Measure Participants | 10 | 15 | 5 | 15 | 8 |
| Median (95% Confidence Interval) [Months] |
NA
|
3.5
|
5.5
|
5.8
|
11.2
|
Adverse Events
| Time Frame | Baseline up to 28 days after last dose of study drug (approximately up to 12 months) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety analysis set included all the participants who received at least 1 dose of study drug and had at least 1 valid post-baseline safety assessment. | |||||||||
| Arm/Group Title | Phase 1b: Binimetinib + Panitumumab | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | |||||
| Arm/Group Description | Participants received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 40 weeks. | Participants with mutant RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 15.4 weeks. | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. | |||||
All Cause Mortality |
||||||||||
| Phase 1b: Binimetinib + Panitumumab | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||
Serious Adverse Events |
||||||||||
| Phase 1b: Binimetinib + Panitumumab | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/10 (30%) | 6/15 (40%) | 2/5 (40%) | 9/15 (60%) | 5/8 (62.5%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 0/10 (0%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||||
| Cardiac disorders | ||||||||||
| Sinus Tachycardia | 0/10 (0%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||||
| Tachycardia | 0/10 (0%) | 1/15 (6.7%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Diarrhoea | 0/10 (0%) | 2/15 (13.3%) | 0/5 (0%) | 2/15 (13.3%) | 0/8 (0%) | |||||
| Abdominal Pain | 1/10 (10%) | 1/15 (6.7%) | 0/5 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Small Intestinal Obstruction | 0/10 (0%) | 1/15 (6.7%) | 1/5 (20%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Vomiting | 1/10 (10%) | 1/15 (6.7%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Abdominal Distension | 0/10 (0%) | 1/15 (6.7%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Colitis | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Intestinal Obstruction | 0/10 (0%) | 0/15 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Nausea | 0/10 (0%) | 1/15 (6.7%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| General disorders | ||||||||||
| Fatigue | 0/10 (0%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||||
| General Physical Health Deterioration | 0/10 (0%) | 0/15 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Pyrexia | 0/10 (0%) | 0/15 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Infections and infestations | ||||||||||
| Pneumonia | 1/10 (10%) | 1/15 (6.7%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Pyelonephritis | 0/10 (0%) | 1/15 (6.7%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Septic Shock | 0/10 (0%) | 0/15 (0%) | 1/5 (20%) | 0/15 (0%) | 0/8 (0%) | |||||
| Skin Infection | 0/10 (0%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||||
| Investigations | ||||||||||
| Blood Creatine Phosphokinase Increased | 0/10 (0%) | 0/15 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Platelet Count Decreased | 0/10 (0%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||||
| Troponin T Increased | 0/10 (0%) | 0/15 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Hypercalcaemia | 0/10 (0%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||||
| Nervous system disorders | ||||||||||
| Transient Ischaemic Attack | 0/10 (0%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||||
| Renal and urinary disorders | ||||||||||
| Acute Kidney Injury | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Hydronephrosis | 0/10 (0%) | 1/15 (6.7%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Dyspnoea | 0/10 (0%) | 0/15 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Hypoxia | 0/10 (0%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||||
| Pneumomediastinum | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Pulmonary Embolism | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Rash Maculo-Papular | 0/10 (0%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||||
| Vascular disorders | ||||||||||
| Deep Vein Thrombosis | 0/10 (0%) | 0/15 (0%) | 1/5 (20%) | 0/15 (0%) | 0/8 (0%) | |||||
| Hypovolaemic Shock | 0/10 (0%) | 0/15 (0%) | 1/5 (20%) | 0/15 (0%) | 0/8 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| Phase 1b: Binimetinib + Panitumumab | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/10 (100%) | 15/15 (100%) | 5/5 (100%) | 15/15 (100%) | 8/8 (100%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 0/10 (0%) | 1/15 (6.7%) | 2/5 (40%) | 4/15 (26.7%) | 2/8 (25%) | |||||
| Leukocytosis | 0/10 (0%) | 1/15 (6.7%) | 0/5 (0%) | 3/15 (20%) | 0/8 (0%) | |||||
| Cardiac disorders | ||||||||||
| Palpitations | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Eye disorders | ||||||||||
| Vision Blurred | 2/10 (20%) | 2/15 (13.3%) | 1/5 (20%) | 2/15 (13.3%) | 0/8 (0%) | |||||
| Chorioretinopathy | 2/10 (20%) | 0/15 (0%) | 0/5 (0%) | 4/15 (26.7%) | 0/8 (0%) | |||||
| Retinal Detachment | 1/10 (10%) | 0/15 (0%) | 2/5 (40%) | 1/15 (6.7%) | 1/8 (12.5%) | |||||
| Retinopathy | 2/10 (20%) | 1/15 (6.7%) | 0/5 (0%) | 1/15 (6.7%) | 1/8 (12.5%) | |||||
| Periorbital Oedema | 2/10 (20%) | 0/15 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Vitreous Floaters | 1/10 (10%) | 1/15 (6.7%) | 0/5 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||||
| Dry Eye | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Eye Swelling | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Eye Discharge | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Iritis | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Visual Impairment | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Diarrhoea | 7/10 (70%) | 9/15 (60%) | 5/5 (100%) | 13/15 (86.7%) | 4/8 (50%) | |||||
| Vomiting | 4/10 (40%) | 8/15 (53.3%) | 4/5 (80%) | 9/15 (60%) | 3/8 (37.5%) | |||||
| Nausea | 5/10 (50%) | 8/15 (53.3%) | 4/5 (80%) | 5/15 (33.3%) | 5/8 (62.5%) | |||||
| Abdominal Pain | 1/10 (10%) | 3/15 (20%) | 4/5 (80%) | 4/15 (26.7%) | 2/8 (25%) | |||||
| Stomatitis | 3/10 (30%) | 1/15 (6.7%) | 0/5 (0%) | 6/15 (40%) | 3/8 (37.5%) | |||||
| Constipation | 2/10 (20%) | 4/15 (26.7%) | 1/5 (20%) | 5/15 (33.3%) | 0/8 (0%) | |||||
| Dry Mouth | 1/10 (10%) | 5/15 (33.3%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Dyspepsia | 2/10 (20%) | 0/15 (0%) | 1/5 (20%) | 2/15 (13.3%) | 1/8 (12.5%) | |||||
| Abdominal Pain Upper | 0/10 (0%) | 2/15 (13.3%) | 0/5 (0%) | 0/15 (0%) | 2/8 (25%) | |||||
| Oral Pain | 0/10 (0%) | 1/15 (6.7%) | 1/5 (20%) | 2/15 (13.3%) | 0/8 (0%) | |||||
| Gastrooesophageal Reflux Disease | 2/10 (20%) | 0/15 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Glossodynia | 0/10 (0%) | 3/15 (20%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Flatulence | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Gastrointestinal Inflammation | 2/10 (20%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Rectal Haemorrhage | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| General disorders | ||||||||||
| Fatigue | 9/10 (90%) | 5/15 (33.3%) | 1/5 (20%) | 5/15 (33.3%) | 5/8 (62.5%) | |||||
| Chills | 3/10 (30%) | 3/15 (20%) | 1/5 (20%) | 1/15 (6.7%) | 2/8 (25%) | |||||
| Oedema Peripheral | 2/10 (20%) | 4/15 (26.7%) | 2/5 (40%) | 1/15 (6.7%) | 1/8 (12.5%) | |||||
| Pyrexia | 2/10 (20%) | 4/15 (26.7%) | 1/5 (20%) | 3/15 (20%) | 0/8 (0%) | |||||
| Asthenia | 0/10 (0%) | 2/15 (13.3%) | 0/5 (0%) | 5/15 (33.3%) | 1/8 (12.5%) | |||||
| Feeling Cold | 3/10 (30%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Face Oedema | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Facial Pain | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Non-Cardiac Chest Pain | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Peripheral Swelling | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Infections and infestations | ||||||||||
| Paronychia | 3/10 (30%) | 0/15 (0%) | 1/5 (20%) | 3/15 (20%) | 1/8 (12.5%) | |||||
| Folliculitis | 0/10 (0%) | 2/15 (13.3%) | 0/5 (0%) | 3/15 (20%) | 0/8 (0%) | |||||
| Conjunctivitis | 1/10 (10%) | 1/15 (6.7%) | 0/5 (0%) | 2/15 (13.3%) | 0/8 (0%) | |||||
| Sepsis | 0/10 (0%) | 1/15 (6.7%) | 0/5 (0%) | 2/15 (13.3%) | 0/8 (0%) | |||||
| Urinary Tract Infection | 1/10 (10%) | 2/15 (13.3%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Nasopharyngitis | 1/10 (10%) | 0/15 (0%) | 1/5 (20%) | 0/15 (0%) | 0/8 (0%) | |||||
| Rash Pustular | 1/10 (10%) | 1/15 (6.7%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Skin Infection | 2/10 (20%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Respiratory Tract Infection | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Septic Shock | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Fungal Skin Infection | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Stoma Site Pain | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Sunburn | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Investigations | ||||||||||
| Blood Creatine Phosphokinase Increased | 5/10 (50%) | 3/15 (20%) | 2/5 (40%) | 6/15 (40%) | 1/8 (12.5%) | |||||
| Aspartate Aminotransferase Increased | 0/10 (0%) | 3/15 (20%) | 1/5 (20%) | 4/15 (26.7%) | 0/8 (0%) | |||||
| Ejection Fraction Decreased | 1/10 (10%) | 2/15 (13.3%) | 2/5 (40%) | 1/15 (6.7%) | 1/8 (12.5%) | |||||
| Blood Creatinine Increased | 0/10 (0%) | 1/15 (6.7%) | 0/5 (0%) | 5/15 (33.3%) | 0/8 (0%) | |||||
| Lipase Increased | 1/10 (10%) | 1/15 (6.7%) | 2/5 (40%) | 1/15 (6.7%) | 1/8 (12.5%) | |||||
| Alanine Aminotransferase Increased | 0/10 (0%) | 2/15 (13.3%) | 1/5 (20%) | 2/15 (13.3%) | 0/8 (0%) | |||||
| Blood Bilirubin Increased | 0/10 (0%) | 2/15 (13.3%) | 1/5 (20%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Weight Decreased | 3/10 (30%) | 0/15 (0%) | 1/5 (20%) | 0/15 (0%) | 0/8 (0%) | |||||
| Amylase Increased | 1/10 (10%) | 0/15 (0%) | 1/5 (20%) | 0/15 (0%) | 1/8 (12.5%) | |||||
| Blood Alkaline Phosphatase Increased | 0/10 (0%) | 2/15 (13.3%) | 0/5 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Intraocular Pressure Increased | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Troponin Increased | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Haemoglobin Decreased | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Hypomagnesaemia | 6/10 (60%) | 2/15 (13.3%) | 0/5 (0%) | 4/15 (26.7%) | 0/8 (0%) | |||||
| Decreased Appetite | 5/10 (50%) | 1/15 (6.7%) | 1/5 (20%) | 4/15 (26.7%) | 0/8 (0%) | |||||
| Hypokalaemia | 0/10 (0%) | 5/15 (33.3%) | 1/5 (20%) | 3/15 (20%) | 0/8 (0%) | |||||
| Dehydration | 2/10 (20%) | 2/15 (13.3%) | 1/5 (20%) | 1/15 (6.7%) | 1/8 (12.5%) | |||||
| Hyponatraemia | 1/10 (10%) | 2/15 (13.3%) | 0/5 (0%) | 2/15 (13.3%) | 0/8 (0%) | |||||
| Hypophosphataemia | 2/10 (20%) | 2/15 (13.3%) | 1/5 (20%) | 0/15 (0%) | 0/8 (0%) | |||||
| Hypoalbuminaemia | 0/10 (0%) | 2/15 (13.3%) | 0/5 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Hypocalcaemia | 0/10 (0%) | 1/15 (6.7%) | 0/5 (0%) | 2/15 (13.3%) | 0/8 (0%) | |||||
| Hyperkalaemia | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Back Pain | 3/10 (30%) | 2/15 (13.3%) | 1/5 (20%) | 1/15 (6.7%) | 1/8 (12.5%) | |||||
| Arthralgia | 3/10 (30%) | 0/15 (0%) | 1/5 (20%) | 0/15 (0%) | 1/8 (12.5%) | |||||
| Pain In Extremity | 2/10 (20%) | 1/15 (6.7%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Arthropathy | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Muscle Spasms | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Muscular Weakness | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Nervous system disorders | ||||||||||
| Dysgeusia | 3/10 (30%) | 0/15 (0%) | 1/5 (20%) | 1/15 (6.7%) | 1/8 (12.5%) | |||||
| Neuropathy Peripheral | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Retinal Migraine | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Somnolence | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Psychiatric disorders | ||||||||||
| Insomnia | 3/10 (30%) | 1/15 (6.7%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Anxiety | 0/10 (0%) | 1/15 (6.7%) | 0/5 (0%) | 1/15 (6.7%) | 1/8 (12.5%) | |||||
| Renal and urinary disorders | ||||||||||
| Haematuria | 1/10 (10%) | 1/15 (6.7%) | 0/5 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Dysuria | 2/10 (20%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Reproductive system and breast disorders | ||||||||||
| Genital Haemorrhage | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Vaginal Haemorrhage | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Dyspnoea | 1/10 (10%) | 0/15 (0%) | 1/5 (20%) | 2/15 (13.3%) | 0/8 (0%) | |||||
| Cough | 1/10 (10%) | 1/15 (6.7%) | 0/5 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Dysphonia | 2/10 (20%) | 0/15 (0%) | 1/5 (20%) | 0/15 (0%) | 0/8 (0%) | |||||
| Oropharyngeal Pain | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Dyspnoea Exertional | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Hiccups | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Nasal Dryness | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Pleuritic Pain | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Productive Cough | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Dermatitis Acneiform | 8/10 (80%) | 5/15 (33.3%) | 1/5 (20%) | 4/15 (26.7%) | 5/8 (62.5%) | |||||
| Rash | 2/10 (20%) | 7/15 (46.7%) | 2/5 (40%) | 9/15 (60%) | 2/8 (25%) | |||||
| Dry Skin | 6/10 (60%) | 1/15 (6.7%) | 1/5 (20%) | 4/15 (26.7%) | 5/8 (62.5%) | |||||
| Rash Maculo-Papular | 5/10 (50%) | 0/15 (0%) | 1/5 (20%) | 2/15 (13.3%) | 4/8 (50%) | |||||
| Skin Fissures | 3/10 (30%) | 0/15 (0%) | 0/5 (0%) | 3/15 (20%) | 2/8 (25%) | |||||
| Pruritus | 1/10 (10%) | 1/15 (6.7%) | 1/5 (20%) | 0/15 (0%) | 1/8 (12.5%) | |||||
| Erythema | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 2/15 (13.3%) | 0/8 (0%) | |||||
| Skin Ulcer | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||||
| Alopecia | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Hirsutism | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Nail Disorder | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Petechiae | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Swelling Face | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Trichorrhexis | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Vascular disorders | ||||||||||
| Hypertension | 2/10 (20%) | 3/15 (20%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
| Hypotension | 1/10 (10%) | 1/15 (6.7%) | 1/5 (20%) | 0/15 (0%) | 0/8 (0%) | |||||
| Vasculitis | 1/10 (10%) | 0/15 (0%) | 0/5 (0%) | 0/15 (0%) | 0/8 (0%) | |||||
Limitations/Caveats
The study used binimetinib 45 mg BID and panitumumab 6 mg/kg intravenous infusion once every second week, there was no planned dose escalation.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01927341
Other Study ID Numbers:
- CMEK162X2116
- C4211008
- 2013-001986-18
First Posted:
Aug 22, 2013
Last Update Posted:
Feb 18, 2021
Last Verified:
Jan 1, 2021