Study of Binimetinib + Nivolumab Plus or Minus Ipilimumab in Patients With Previously Treated Microsatellite-stable (MSS) Metastatic Colorectal Cancer With RAS Mutation
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT03271047
Collaborator
Bristol-Myers Squibb (Industry)
75
50
4
40.3
1.5
0
Study Details
Study Description
Brief Summary
This is a multicenter, open-label, Phase 1B/2 study to evaluate the safety and assess the preliminary anti-tumor activity of binimetinib administered in combination with nivolumab or nivolumab + ipilimumab in adult patients with advanced metastatic colorectal cancer (mCRC) with microsatellite stable (MSS) disease and presence of a RAS mutation that have received at least one prior line of therapy and no more than 2 prior lines of therapy. The study contains a Phase 1b period to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) and schedule of binimetinib followed by a randomized Phase 2 period to assess the efficacy of the combinations.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
75 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
In phase 1 it is sequential and then in phase 2 it is parallel.In phase 1 it is sequential and then in phase 2 it is parallel.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label Phase 1b/2 Study of Binimetinib Administered in Combination With Nivolumab or Nivolumab Plus Ipilimumab in Patients With Previously Treated Microsatellite-stable (MSS) Metastatic Colorectal Cancer With RAS Mutation
Actual Study Start Date
:
Oct 18, 2017
Actual Primary Completion Date
:
Oct 13, 2020
Actual Study Completion Date
:
Feb 25, 2021
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase 1b / Arm 1A binimetinib + nivolumab |
Drug: binimetinib
Orally, twice daily.
Drug: nivolumab
Intravenously (IV) every 4 weeks (Q4W)
|
| Experimental: Phase 1b / Arm 1B binimetinib + nivolumab + ipilimumab |
Drug: binimetinib
Orally, twice daily.
Drug: nivolumab
Intravenously (IV) every 4 weeks (Q4W)
Drug: ipilimumab
intravenously (IV) every 8 weeks (Q8W)
|
| Experimental: Phase 2 / Arm 2A binimetinib + nivolumab |
Drug: binimetinib
Orally, twice daily.
Drug: nivolumab
Intravenously (IV) every 4 weeks (Q4W)
|
| Experimental: Phase 2 / Arm 2B binimetinib + nivolumab + ipilimumab |
Drug: binimetinib
Orally, twice daily.
Drug: nivolumab
Intravenously (IV) every 4 weeks (Q4W)
Drug: ipilimumab
intravenously (IV) every 8 weeks (Q8W)
|
Outcome Measures
Primary Outcome Measures
- Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLT) [Cycle 1: Day 1 up to Day 28]
DLT:Adverse event(AE)/abnormal laboratory assessed unrelated-disease,disease progression,intercurrent illness/concomitant medication/therapies resulting inability tolerate 75% dose intensity in Cycle 1.Total bilirubin(TBL)grade(G)>=3 (>3.0*upper limit of normal[ULN)]);AST/ALT>5-8*ULN>5 days,>8*ULN,>3*ULN concurrent TBL>2*ULN;G>=3 serum creatinine,CK elevation,ECG QTcF prolonged,G3 troponin,electrolyte>72 hours,G3/4 amylase/lipase.G4 ANC,platelet count>7 days;G3/4 platelet count,other AE except lymphopenia.G>=3 retinopathy,other disorder>21 days;G2 uveitis/eye pain/blurred vision/decreased visual acuity;G4 other disorder.Decrease LVEF>10% G>=3 cardiac disorders.G3/4 hypertension.G3 fatigue>=7 days,hypersensitivity,infusion reaction,fever>=72 hours/hemodynamic compromise,endocrinopathy.G>=2 interstitial lung disease/pneumonitis;G3 bronchospasm.G3/4 rash,hand foot skin reaction,photosensitivity.G3 colitis;G3/4 diarrhea,nausea/vomiting.Neurologic G3.Other hematologic/nonhematolic G>=3 AE.
- Phase 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 [From start of the treatment until disease progression, death or initiation of new anticancer therapy, whichever occurred first (Phase 2: maximum up to 26 months approximately)]
ORR was defined as the percentage of participants who achieved a best overall response (BOR) of complete response (CR) or partial response (PR) as determined by investigator per RECIST v1.1. As per RECIST v1.1, CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (<)10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-progressive disease (PD). PD was defined as at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was considered progression.
Secondary Outcome Measures
- Phase 1b: Objective Response Rate (ORR) Per RECIST v1.1 [From start of the treatment until disease progression, death or initiation of new anticancer therapy, whichever occurred first (Phase 1b: maximum up to 9 months approximately)]
ORR was defined as the percentage of participants who achieved a BOR of CR or PR as determined by investigator per RECIST v1.1. As per RECIST v1.1, CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. PR was defined as at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the baseline sum of diameters. Non-target lesions must be non-PD. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
- Duration of Response (DOR) as Per RECIST v1.1 [From date of first documented CR/PR to date of first documented PD, death or initiation of new anticancer therapy, whichever occurred first (Phase 1b: maximum up to 9 months approximately, Phase 2: maximum up to 26 months approximately)]
DOR was defined as the time between the date of the first documented confirmed response (PR or CR) and the date of the first documented progression or death due to any cause. As per RECIST v1.1: CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes short axis measures <10 mm. PR was defined as at least 30% decrease in sum of measures (tumor lesions- longest diameter and nodes- short axis) of target lesions, taking as reference baseline sum of diameters. PD was defined as at least 20% increase in sum of diameters of measured lesions taking as references smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion. Unequivocal progression of existing non-target lesions.
- Percentage of Participants With Complete Response as Per RECIST v1.1 [From start of the treatment until disease progression, death or initiation of new anticancer therapy, whichever occurred first (Phase 1b: maximum up to 9 months approximately and Phase 2: maximum up to 26 months approximately)]
Complete response as per RECIST v1.1 was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm.
- Number of Participants With Treatment-Emergent Adverse Events (TEAE) Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 [From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (Phase 1b: maximum up to 9 months approximately and Phase 2: maximum up to 26 months approximately)]
AE: any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE: AE resulting in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs: events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy minus 1 day, whichever occurred first. TEAE graded by CTCAE grade 4.03: Grade 3: severe/medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care activities of daily living (ADL); Grade 4: life-threatening consequence, urgent intervention indicated. In this outcome measure, number of participants with 'all grades' and 'Grade 3/4' were reported.
- Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03: Hematology and Coagulation [Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately)]
Hematological parameters included: Hemoglobin graded high, Hemoglobin graded low, Platelets count graded low, White Blood Cell (WBC) graded high, WBC graded low, Neutrophils graded low, Lymphocytes graded high, Lymphocytes graded low. Coagulation parameters included: International Normalized Ratio (INR) graded high, Activated Partial Thromboplastin Time (aPTT) graded high. Test abnormalities were graded by CTCAE v4.03 as Grade 1=mild; Grade 2=moderate; Grade 3/Grade 4=severe/life-threatening. A grade 0 was assigned for all non-missing values not graded as 1 or higher. If value was graded >=1 but falls within the normal range, the grade was reset to 0. Categories with at least 1 non-zero data values are reported.
- Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on Normal Range: Hematology and Coagulation [Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately)]
Hematology parameters: Basophils, Eosinophils, Hematocrit, Monocytes, Red blood cells (RBC). Coagulation parameters: Prothrombin Time. Laboratory values were as per laboratory normal ranges. Values above range were reported as high and values below range as low. Laboratory parameters were graded based on laboratory normal ranges as low, normal, high and missing are reported in this outcome measure. Categories with at least 1 non-zero data values are reported.
- Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on CTCAE v4.03: Chemistry [Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately)]
Abnormalities: Albumin graded low, Alkaline phosphatase (ALP) graded high, Alanine aminotransferase (ALT) graded high, Aspartate aminotransferase (AST) graded high, Bilirubin graded high, Amylase graded high, Creatinine graded high, Corrected calcium graded high, Creatine Kinase (CK) graded high, Glucose graded high, Glucose graded low, Lipase graded high, Magnesium graded high, Magnesium graded low, Potassium graded high, Potassium graded low, Sodium graded high and Sodium graded low. Test abnormalities were graded by CTCAE v4.03 as Grade 1=mild; Grade 2=moderate; Grade 3/Grade 4=severe/life-threatening. A grade 0 was assigned for all non-missing values not graded as 1 or higher. If value was graded >=1 but falls within the normal range, the grade was reset to 0. Categories with at least 1 non-zero data values are reported.
- Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on Normal Range: Chemistry and Thyroid Function [Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately)]
Chemistry laboratory parameters: Blood urea nitrogen (BUN), Total protein, Chloride, Cancer antigen 19-9 (CA 19-9), Brain natriuretic peptide (BNP), Bicarbonate, Direct bilirubin, Carcinoembryonic antigen (CEA), Lactate dehydrogenase (LDH), Uric acid, Troponin I. Thyroid panel laboratory parameters: Thyroid-stimulating hormone (TSH), Free triiodothyronine (T3), Free thyroxine (T4). Laboratory values were as per laboratory normal ranges. Values above range were reported as high and values below range as low. Shift in chemistry and thyroid panel severity from baseline grade low, normal, high and missing to the post baseline grades as low, normal, high and missing are reported in this outcome measure. Categories with at least 1 non-zero data values are reported.
- Number of Participants With Abnormal Hepatic Laboratory Values [Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately)]
Criteria for abnormal hepatic laboratory parameters: Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT): >3* upper limit of normal (ULN), >5*ULN, >8*ULN, >10*ULN, >20*ULN; Total bilirubin (TBL) >1.5*ULN, >2*ULN; Alkaline phosphatase (ALP) >2*ULN, >3*ULN. Categories with at least 1 non-zero data values are reported.
- Concentration Versus Time Summary of Plasma Concentration of Binimetinib [1.5 hours post dose of binimetinib on Day 1, 15 of Cycle 1; pre dose of binimetinib on Day 15 of Cycle 1, 2, 3, 4, 5]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria
-
Measurable, histologically/cytologically confirmed metastatic colorectal cancer (mCRC).
-
Able to provide a sufficient amount of representative tumor specimen for central laboratory testing of RAS mutation status and microsatellite stable (MSS).
-
If a fresh tissue sample is provided, a blood sample is required.
-
Metastatic colorectal cancer (mCRC) categorized as microsatellite stable (MSS) by polymerase chain reaction (PCR) per local assay at any time prior to Screening or by the central laboratory.
-
RAS mutation per local assay at any time prior to Screening or by the central laboratory.
-
Have received at least 1 prior line of therapy and meets at least one of the following criteria:
-
were unable to tolerate the prior first-line regimen
-
experienced disease progression during or after prior first-line regimen for metastatic disease
-
progressed during or within 3 months of completing adjuvant chemotherapy. Note: Generally, treatments that are separated by an event of progression are considered different regimens.
-
Have received no more than 2 prior lines of therapy (maintenance therapy given in the metastatic setting will not be considered a separate regimen). Generally, treatments that are separated by an event of progression are considered different regimens.
-
Adequate bone marrow, cardiac, kidney and liver function
-
Able to take oral medications
-
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
-
Female patients are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks, or must agree to take appropriate precautions to avoid pregnancy from screening through follow-up if of child-bearing potential
-
Non-sterile male patients who are sexually active with female partners of childbearing potential must agree to follow instructions for acceptable or highly effective method(s) of contraception for the duration of study treatment and for 7 months after the last dose of study treatment with nivolumab
Key Exclusion Criteria
-
Prior treatment with any MEK inhibitor, an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
-
Any untreated central nervous system (CNS) lesion.
-
Patients with an active, known or suspected autoimmune disease. Patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
-
Known history of retinal vein occlusion (RVO).
-
Known history of Gilbert's syndrome.
-
Pregnant or breastfeeding females.
-
Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to first day of study treatment:
-
History of thromboembolic or cerebrovascular events ≤ 6 months prior to starting study treatment, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis or pulmonary emboli.
-
Uncontrolled hypertension defined as persistent systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg despite current therapy.
-
Concurrent neuromuscular disorder that is associated with the potential of elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
-
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).
-
Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be performed at sites where mandated locally.
-
Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection, and/or detectable virus.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UCLA Hematology/Oncology | Los Angeles | California | United States | 90095 |
| 2 | UCLA Hematology/Oncology - Santa Monica | Santa Monica | California | United States | 90404 |
| 3 | Christiana Care Health Services, Helen F. Graham Cancer Center Pharmacy, Suite 3200 | Newark | Delaware | United States | 19713 |
| 4 | Christiana Care Health Services, Helen F. Graham Cancer Center | Newark | Delaware | United States | 19713 |
| 5 | Christiana Care Oncology Hematology, Helen F Graham Cancer Center, Suite 2400 | Newark | Delaware | United States | 19713 |
| 6 | Medical Oncology Hematology Consultants, PA, Helen F. Graham Cancer Center | Newark | Delaware | United States | 19713 |
| 7 | Christiana Care Health Services, Christiana Hospital | Newark | Delaware | United States | 19718 |
| 8 | Georgetown University Medical Center Department of Pharmacy, Research | Washington | District of Columbia | United States | 20007 |
| 9 | Georgetown University Medical Center | Washington | District of Columbia | United States | 20007 |
| 10 | Hematology Oncology Associates of the Treasure Coast | Port Saint Lucie | Florida | United States | 34952 |
| 11 | Indiana CTSI Clinical Research Center (ICRC) | Indianapolis | Indiana | United States | 46202 |
| 12 | Indiana University Health Hospital | Indianapolis | Indiana | United States | 46202 |
| 13 | Indiana University Health Melvin and Bren Simon Cancer Center | Indianapolis | Indiana | United States | 46202 |
| 14 | Investigational Drug Services IUHSCC | Indianapolis | Indiana | United States | 46202 |
| 15 | Sidney &Lois Eskenazi Hospital | Indianapolis | Indiana | United States | 46202 |
| 16 | Spring Mill Medical Center | Indianapolis | Indiana | United States | 46290 |
| 17 | Siteman Cancer Center - West County | Creve Coeur | Missouri | United States | 63141 |
| 18 | Siteman Cancer Center - North County | Florissant | Missouri | United States | 63031 |
| 19 | Center for Outpatient Health (Dermatology Clinic) | Saint Louis | Missouri | United States | 63108 |
| 20 | Center for Outpatient Health (Ophthalmology Clinic) | Saint Louis | Missouri | United States | 63108 |
| 21 | Barnes-Jewish Hospital | Saint Louis | Missouri | United States | 63110 |
| 22 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 23 | Siteman Cancer Center - South County | Saint Louis | Missouri | United States | 63129 |
| 24 | Siteman Cancer Center - Barnes St. Peters | Saint Peters | Missouri | United States | 63376 |
| 25 | Hospital of the University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 26 | Investigational Drug Service of the University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 27 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | 19111 |
| 28 | Sarah Cannon Research Institute | Chattanooga | Tennessee | United States | 37404 |
| 29 | SCRI Tennessee Oncology Chattanooga | Chattanooga | Tennessee | United States | 37404 |
| 30 | Tennessee Oncology, PLLC | Cleveland | Tennessee | United States | 37311 |
| 31 | Tennessee Oncology NASH - SCRI - PPDS | Nashville | Tennessee | United States | 37203 |
| 32 | The Sarah Cannon Research Institute. | Nashville | Tennessee | United States | 37203 |
| 33 | The University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 34 | UZ Leuven - Dermatology | Leuven | Belgium | 3000 | |
| 35 | UZ Leuven - Ophthalmology | Leuven | Belgium | 3000 | |
| 36 | UZ Leuven | Leuven | Belgium | 3000 | |
| 37 | The Netherlands Cancer Institute Antoni Van Leeuwenhoek | Amsterdam | Noord-holland | Netherlands | 1066 CX |
| 38 | OLVG locatie Oost | Amsterdam | Noord-holland | Netherlands | 1091 AC |
| 39 | Amsterdam Medical Center (AMC) | Amsterdam | Noord-holland | Netherlands | 1105 AZ |
| 40 | Hospital Universitario Vall d'Hebron | Barcelona | Spain | 08035 | |
| 41 | Hospital Universitario Vall d'Hebrón - PPDS | Barcelona | Spain | 08035 | |
| 42 | Hospital General Universitario Gregorio Marañon | Madrid | Spain | 28007 | |
| 43 | Clinica Rementeria | MAdrid | Spain | 28010 | |
| 44 | Hospital Universitario 12 Octubre | Madrid | Spain | 28041 | |
| 45 | Hospital HM Universitario Sanchinarro, CIOCC | Madrid | Spain | 28050 | |
| 46 | Royal Marsden Hospital - London | London | London, CITY OF | United Kingdom | SW3 6JJ |
| 47 | Churchill Hospital | Oxford | Oxfordshire | United Kingdom | OX3 7LE |
| 48 | Royal Marsden Hospital NHS Foundation Trust | Surrey | Sutton | United Kingdom | SM2 5PT |
| 49 | Royal Marsden Hospital NHS Foundation Trust | London | United Kingdom | SW3 6JJ | |
| 50 | Royal Marsden Hospital -Fulham Road | London | United Kingdom | SW36JJ |
Sponsors and Collaborators
- Pfizer
- Bristol-Myers Squibb
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT03271047
Other Study ID Numbers:
- ARRAY-162-202
- C4211004
- 2017-003464-12
First Posted:
Sep 1, 2017
Last Update Posted:
Jan 4, 2022
Last Verified:
Dec 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | This study included 2 phases: Phase 1b and Phase 2. The recommended dose for Phase 2 (RP2D) of binimetinib was determined in Phase 1b (dose finding phase). |
| Arm/Group Title | Phase 1b: Nivolumab+Binimetinib | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Phase 2: Nivolumab+Binimetinib | Phase 2: Nivolumab+Ipilimumab+Binimetinib |
|---|---|---|---|---|
| Arm/Group Description | Participants with previously treated microsatellite-stable (MSS) metastatic colorectal cancer with rat sarcoma virus (RAS) mutation received binimetinib at a starting dose of 45 milligrams (mg) tablet orally twice daily (BID) along with 480 mg intravenously (IV) dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 milligram per kilogram (mg/kg) IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| Period Title: Phase 1b: Dose Finding Period | ||||
| STARTED | 10 | 11 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 10 | 11 | 0 | 0 |
| Period Title: Phase 1b: Dose Finding Period | ||||
| STARTED | 0 | 0 | 27 | 27 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 27 | 27 |
Baseline Characteristics
| Arm/Group Title | Phase 1b: Nivolumab+Binimetinib | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Phase 2: Nivolumab+Binimetinib | Phase 2: Nivolumab+Ipilimumab+Binimetinib | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. | Total of all reporting groups |
| Overall Participants | 10 | 11 | 27 | 27 | 75 |
| Age (Count of Participants) | |||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
5
50%
|
9
81.8%
|
19
70.4%
|
20
74.1%
|
53
70.7%
|
| >=65 years |
5
50%
|
2
18.2%
|
8
29.6%
|
7
25.9%
|
22
29.3%
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
2
20%
|
4
36.4%
|
11
40.7%
|
10
37%
|
27
36%
|
| Male |
8
80%
|
7
63.6%
|
16
59.3%
|
17
63%
|
48
64%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
1
1.3%
|
| Not Hispanic or Latino |
10
100%
|
11
100%
|
21
77.8%
|
23
85.2%
|
65
86.7%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
5
18.5%
|
4
14.8%
|
9
12%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
1
1.3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
10%
|
0
0%
|
1
3.7%
|
1
3.7%
|
3
4%
|
| White |
9
90%
|
11
100%
|
21
77.8%
|
23
85.2%
|
64
85.3%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
4
14.8%
|
3
11.1%
|
7
9.3%
|
Outcome Measures
| Title | Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLT) |
|---|---|
| Description | DLT:Adverse event(AE)/abnormal laboratory assessed unrelated-disease,disease progression,intercurrent illness/concomitant medication/therapies resulting inability tolerate 75% dose intensity in Cycle 1.Total bilirubin(TBL)grade(G)>=3 (>3.0*upper limit of normal[ULN)]);AST/ALT>5-8*ULN>5 days,>8*ULN,>3*ULN concurrent TBL>2*ULN;G>=3 serum creatinine,CK elevation,ECG QTcF prolonged,G3 troponin,electrolyte>72 hours,G3/4 amylase/lipase.G4 ANC,platelet count>7 days;G3/4 platelet count,other AE except lymphopenia.G>=3 retinopathy,other disorder>21 days;G2 uveitis/eye pain/blurred vision/decreased visual acuity;G4 other disorder.Decrease LVEF>10% G>=3 cardiac disorders.G3/4 hypertension.G3 fatigue>=7 days,hypersensitivity,infusion reaction,fever>=72 hours/hemodynamic compromise,endocrinopathy.G>=2 interstitial lung disease/pneumonitis;G3 bronchospasm.G3/4 rash,hand foot skin reaction,photosensitivity.G3 colitis;G3/4 diarrhea,nausea/vomiting.Neurologic G3.Other hematologic/nonhematolic G>=3 AE. |
| Time Frame | Cycle 1: Day 1 up to Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Dose-Determining Set (DDS) included all participants in Phase 1b who experienced a DLT or receive at least 75% of the planned binimetinib dose intensity during Cycle 1. |
| Arm/Group Title | Phase 1b: Nivolumab+Binimetinib | Phase 1b: Nivolumab+Ipilimumab+Binimetinib |
|---|---|---|
| Arm/Group Description | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. |
| Measure Participants | 9 | 11 |
| Count of Participants [Participants] |
1
10%
|
2
18.2%
|
| Title | Phase 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 |
|---|---|
| Description | ORR was defined as the percentage of participants who achieved a best overall response (BOR) of complete response (CR) or partial response (PR) as determined by investigator per RECIST v1.1. As per RECIST v1.1, CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (<)10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-progressive disease (PD). PD was defined as at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was considered progression. |
| Time Frame | From start of the treatment until disease progression, death or initiation of new anticancer therapy, whichever occurred first (Phase 2: maximum up to 26 months approximately) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants randomized to study treatment in Phase 2. |
| Arm/Group Title | Phase 2: Nivolumab+Binimetinib | Phase 2: Nivolumab+Ipilimumab+Binimetinib |
|---|---|---|
| Arm/Group Description | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| Measure Participants | 27 | 27 |
| Number (95% Confidence Interval) [Percentage of participants] |
0.0
0%
|
7.4
67.3%
|
| Title | Phase 1b: Objective Response Rate (ORR) Per RECIST v1.1 |
|---|---|
| Description | ORR was defined as the percentage of participants who achieved a BOR of CR or PR as determined by investigator per RECIST v1.1. As per RECIST v1.1, CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. PR was defined as at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the baseline sum of diameters. Non-target lesions must be non-PD. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. |
| Time Frame | From start of the treatment until disease progression, death or initiation of new anticancer therapy, whichever occurred first (Phase 1b: maximum up to 9 months approximately) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of any study treatment in Phase 1b. |
| Arm/Group Title | Phase 1b: Nivolumab+Binimetinib | Phase 1b: Nivolumab+Ipilimumab+Binimetinib |
|---|---|---|
| Arm/Group Description | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. |
| Measure Participants | 10 | 11 |
| Number (95% Confidence Interval) [Percentage of participants] |
0.0
0%
|
0.0
0%
|
| Title | Duration of Response (DOR) as Per RECIST v1.1 |
|---|---|
| Description | DOR was defined as the time between the date of the first documented confirmed response (PR or CR) and the date of the first documented progression or death due to any cause. As per RECIST v1.1: CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes short axis measures <10 mm. PR was defined as at least 30% decrease in sum of measures (tumor lesions- longest diameter and nodes- short axis) of target lesions, taking as reference baseline sum of diameters. PD was defined as at least 20% increase in sum of diameters of measured lesions taking as references smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion. Unequivocal progression of existing non-target lesions. |
| Time Frame | From date of first documented CR/PR to date of first documented PD, death or initiation of new anticancer therapy, whichever occurred first (Phase 1b: maximum up to 9 months approximately, Phase 2: maximum up to 26 months approximately) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants who received at least 1 dose of any study drug in Phase 1b and all participants randomized to study treatment in Phase 2. Here, "Overall Number of Participants Analyzed" signifies number of participants who achieved an objective response. There were no participants who had event in Phase 1b and Nivolumab and Binimetinib group of Phase 2. |
| Arm/Group Title | Phase 1b: Nivolumab+Binimetinib | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Phase 2: Nivolumab+Binimetinib | Phase 2: Nivolumab+Ipilimumab+Binimetinib |
|---|---|---|---|---|
| Arm/Group Description | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| Measure Participants | 0 | 0 | 0 | 2 |
| Median (95% Confidence Interval) [Months] |
11.4
|
| Title | Percentage of Participants With Complete Response as Per RECIST v1.1 |
|---|---|
| Description | Complete response as per RECIST v1.1 was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. |
| Time Frame | From start of the treatment until disease progression, death or initiation of new anticancer therapy, whichever occurred first (Phase 1b: maximum up to 9 months approximately and Phase 2: maximum up to 26 months approximately) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants who received at least 1 dose of any study drug in Phase 1b and all participants randomized to study treatment in Phase 2. |
| Arm/Group Title | Phase 1b: Nivolumab+Binimetinib | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Phase 2: Nivolumab+Binimetinib | Phase 2: Nivolumab+Ipilimumab+Binimetinib |
|---|---|---|---|---|
| Arm/Group Description | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| Measure Participants | 10 | 11 | 27 | 27 |
| Number [Percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Treatment-Emergent Adverse Events (TEAE) Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 |
|---|---|
| Description | AE: any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE: AE resulting in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs: events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy minus 1 day, whichever occurred first. TEAE graded by CTCAE grade 4.03: Grade 3: severe/medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care activities of daily living (ADL); Grade 4: life-threatening consequence, urgent intervention indicated. In this outcome measure, number of participants with 'all grades' and 'Grade 3/4' were reported. |
| Time Frame | From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (Phase 1b: maximum up to 9 months approximately and Phase 2: maximum up to 26 months approximately) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety set included of all participants who received at least 1 dose of study drug. |
| Arm/Group Title | Phase 1b: Nivolumab+Binimetinib | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Phase 2: Nivolumab+Binimetinib | Phase 2: Nivolumab+Ipilimumab+Binimetinib |
|---|---|---|---|---|
| Arm/Group Description | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| Measure Participants | 10 | 11 | 27 | 27 |
| Treatment emergent AEs- All grades |
10
100%
|
11
100%
|
27
100%
|
27
100%
|
| Treatment emergent SAEs- All grades |
5
50%
|
6
54.5%
|
12
44.4%
|
11
40.7%
|
| Treatment emergent AEs- Grade 3/4 |
6
60%
|
8
72.7%
|
19
70.4%
|
21
77.8%
|
| Treatment emergent SAEs- Grade 3/4 |
5
50%
|
6
54.5%
|
11
40.7%
|
10
37%
|
| Title | Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03: Hematology and Coagulation |
|---|---|
| Description | Hematological parameters included: Hemoglobin graded high, Hemoglobin graded low, Platelets count graded low, White Blood Cell (WBC) graded high, WBC graded low, Neutrophils graded low, Lymphocytes graded high, Lymphocytes graded low. Coagulation parameters included: International Normalized Ratio (INR) graded high, Activated Partial Thromboplastin Time (aPTT) graded high. Test abnormalities were graded by CTCAE v4.03 as Grade 1=mild; Grade 2=moderate; Grade 3/Grade 4=severe/life-threatening. A grade 0 was assigned for all non-missing values not graded as 1 or higher. If value was graded >=1 but falls within the normal range, the grade was reset to 0. Categories with at least 1 non-zero data values are reported. |
| Time Frame | Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety set included of all participants who received at least 1 dose of study drug. Here "Number Analyzed" signifies number of participants evaluable for specified rows. |
| Arm/Group Title | Phase 1b: Nivolumab+Binimetinib | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Phase 2: Nivolumab+Binimetinib | Phase 2: Nivolumab+Ipilimumab+Binimetinib |
|---|---|---|---|---|
| Arm/Group Description | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| Measure Participants | 10 | 11 | 27 | 27 |
| Hemoglobin- CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) |
3
30%
|
3
27.3%
|
4
14.8%
|
5
18.5%
|
| Hemoglobin- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) |
2
20%
|
2
18.2%
|
6
22.2%
|
10
37%
|
| Hemoglobin- CTCAE Graded Low: Grade 0 (at baseline) to Grade 2 (at post baseline) |
2
20%
|
1
9.1%
|
2
7.4%
|
1
3.7%
|
| Hemoglobin- CTCAE Graded Low: Grade 0 (at baseline) to Grade 3 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Hemoglobin- CTCAE Graded Low: Grade 1 (at baseline) to Grade 0 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Hemoglobin- CTCAE Graded Low: Grade 1 (at baseline) to Grade 1 (at post baseline) |
1
10%
|
4
36.4%
|
4
14.8%
|
4
14.8%
|
| Hemoglobin- CTCAE Graded Low: Grade 1 (at baseline) to Grade 2 (at post baseline) |
2
20%
|
0
0%
|
3
11.1%
|
1
3.7%
|
| Hemoglobin- CTCAE Graded Low: Grade 1 (at baseline) to Grade 3 (at post baseline) |
0
0%
|
1
9.1%
|
1
3.7%
|
1
3.7%
|
| Hemoglobin- CTCAE Graded Low: Grade 1 (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Hemoglobin- CTCAE Graded Low: Grade 2 (at baseline) to Grade 2 (at post baseline) |
3
30%
|
5
45.5%
|
||
| Hemoglobin- CTCAE Graded Low: Grade 2 (at baseline) to Grade 3 (at post baseline) |
1
10%
|
0
0%
|
||
| Hemoglobin- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) |
10
100%
|
11
100%
|
26
96.3%
|
26
96.3%
|
| Hemoglobin- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) |
0
0%
|
0
0%
|
0
0%
|
1
3.7%
|
| Hemoglobin- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Lymphocytes - CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) |
6
60%
|
7
63.6%
|
11
40.7%
|
11
40.7%
|
| Lymphocytes- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) |
0
0%
|
0
0%
|
2
7.4%
|
4
14.8%
|
| Lymphocytes- CTCAE Graded Low: Grade 0 (at baseline) to Grade 2 (at post baseline) |
0
0%
|
2
18.2%
|
4
14.8%
|
6
22.2%
|
| Lymphocytes- CTCAE Graded Low: Grade 0 (at baseline) to Grade 3 (at post baseline) |
1
10%
|
0
0%
|
3
11.1%
|
1
3.7%
|
| Lymphocytes- CTCAE Graded Low: Grade 0 (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Lymphocytes- CTCAE Graded Low: Grade 1 (at baseline) to Grade 0 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
|
| Lymphocytes- CTCAE Graded Low: Grade 1 (at baseline) to Grade 2 (at post baseline) |
1
10%
|
1
9.1%
|
0
0%
|
|
| Lymphocytes- CTCAE Graded Low: Grade 1 (at baseline) to Grade 3 (at post baseline) |
0
0%
|
1
9.1%
|
0
0%
|
|
| Lymphocytes- CTCAE Graded Low: Grade 2 (at baseline) to Grade 0 (at post baseline) |
0
0%
|
1
9.1%
|
0
0%
|
|
| Lymphocytes- CTCAE Graded Low: Grade 2 (at baseline) to Grade 2 (at post baseline) |
1
10%
|
1
9.1%
|
2
7.4%
|
|
| Lymphocytes- CTCAE Graded Low: Grade 2 (at baseline) to Grade 3 (at post baseline) |
1
10%
|
1
9.1%
|
2
7.4%
|
|
| Lymphocytes- CTCAE Graded Low: Grade 3 (at baseline) to Grade 0 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
|
| Lymphocytes- CTCAE Graded Low: Grade 3 (at baseline) to Grade 2 (at post baseline) |
0
0%
|
1
9.1%
|
0
0%
|
|
| Lymphocytes- CTCAE Graded Low: Grade 3 (at baseline) to Grade 3 (at post baseline) |
1
10%
|
0
0%
|
0
0%
|
|
| Lymphocytes- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) |
9
90%
|
11
100%
|
25
92.6%
|
26
96.3%
|
| Lymphocytes- CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) |
1
10%
|
0
0%
|
1
3.7%
|
1
3.7%
|
| Lymphocytes- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Neutrophils- CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) |
9
90%
|
11
100%
|
23
85.2%
|
26
96.3%
|
| Neutrophils- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
1
3.7%
|
| Neutrophils- CTCAE Graded Low: Grade 0 (at baseline) to Grade 2 (at post baseline) |
1
10%
|
0
0%
|
0
0%
|
0
0%
|
| Neutrophils- CTCAE Graded Low: Grade 0 (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Neutrophils- CTCAE Graded Low: Grade 1 (at baseline) to Grade 0 (at post baseline) |
1
10%
|
|||
| Neutrophils- CTCAE Graded Low: Grade 1 (at baseline) to Grade 3 (at post baseline) |
1
10%
|
|||
| Platelets- CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) |
8
80%
|
9
81.8%
|
21
77.8%
|
22
81.5%
|
| Platelets- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) |
2
20%
|
1
9.1%
|
3
11.1%
|
4
14.8%
|
| Platelets- CTCAE Graded Low: Grade 0 (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
2
7.4%
|
0
0%
|
| Platelets- CTCAE Graded Low: Grade 1 (at baseline) to Grade 0 (at post baseline) |
1
10%
|
0
0%
|
0
0%
|
|
| Platelets- CTCAE Graded Low: Grade 1 (at baseline) to Grade 1 (at post baseline) |
0
0%
|
1
9.1%
|
1
3.7%
|
|
| WBC- CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) |
9
90%
|
11
100%
|
21
77.8%
|
24
88.9%
|
| WBC- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) |
0
0%
|
0
0%
|
2
7.4%
|
0
0%
|
| WBC- CTCAE Graded Low: Grade 0 (at baseline) to Grade 2 (at post baseline) |
1
10%
|
0
0%
|
1
3.7%
|
2
7.4%
|
| WBC- CTCAE Graded Low: Grade 0 (at baseline) to Grade 4 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| WBC- CTCAE Graded Low: Grade 0 (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| WBC- CTCAE Graded Low: Grade 1 (at baseline) to Grade 1 (at post baseline) |
1
10%
|
0
0%
|
||
| WBC- CTCAE Graded Low: Grade 1 (at baseline) to Grade 2 (at post baseline) |
0
0%
|
1
9.1%
|
||
| WBC- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) |
10
100%
|
11
100%
|
26
96.3%
|
27
100%
|
| WBC- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| aPTT- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) |
6
60%
|
8
72.7%
|
16
59.3%
|
17
63%
|
| aPTT- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) |
3
30%
|
2
18.2%
|
6
22.2%
|
6
22.2%
|
| aPTT- CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) |
1
10%
|
0
0%
|
2
7.4%
|
1
3.7%
|
| aPTT- CTCAE Graded High: Grade 1 (at baseline) to Grade 0 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
|
| aPTT- CTCAE Graded High: Grade 1 (at baseline) to Grade 1 (at post baseline) |
1
10%
|
1
9.1%
|
1
3.7%
|
|
| aPTT- CTCAE Graded High: Grade 1 (at baseline) to Grade 3 (at post baseline) |
0
0%
|
1
9.1%
|
0
0%
|
|
| aPTT- CTCAE Graded High: Grade 1 (at baseline) to Missing (at post baseline) |
0
0%
|
1
9.1%
|
0
0%
|
|
| aPTT- CTCAE Graded High: Missing (at baseline) to Grade 0 (at post baseline) |
1
10%
|
|||
| INR- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) |
5
50%
|
6
54.5%
|
16
59.3%
|
13
48.1%
|
| INR- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) |
4
40%
|
2
18.2%
|
4
14.8%
|
4
14.8%
|
| INR- CTCAE Graded High: Grade 1 (at baseline) to Grade 0 (at post baseline) |
0
0%
|
1
9.1%
|
1
3.7%
|
1
3.7%
|
| INR- CTCAE Graded High: Grade 1 (at baseline) to Grade 1 (at post baseline) |
1
10%
|
1
9.1%
|
5
18.5%
|
8
29.6%
|
| INR- CTCAE Graded High: Grade 1 (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| INR- CTCAE Graded High: Grade 2 (at baseline) to Grade 2 (at post baseline) |
1
10%
|
|||
| INR- CTCAE Graded High: Missing (at baseline) to Grade 0 (at post baseline) |
1
10%
|
| Title | Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on Normal Range: Hematology and Coagulation |
|---|---|
| Description | Hematology parameters: Basophils, Eosinophils, Hematocrit, Monocytes, Red blood cells (RBC). Coagulation parameters: Prothrombin Time. Laboratory values were as per laboratory normal ranges. Values above range were reported as high and values below range as low. Laboratory parameters were graded based on laboratory normal ranges as low, normal, high and missing are reported in this outcome measure. Categories with at least 1 non-zero data values are reported. |
| Time Frame | Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety set included of all participants who received at least 1 dose of study drug. Here "Number Analyzed" signifies number of participants evaluable for specified rows. |
| Arm/Group Title | Phase 1b: Nivolumab+Binimetinib | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Phase 2: Nivolumab+Binimetinib | Phase 2: Nivolumab+Ipilimumab+Binimetinib |
|---|---|---|---|---|
| Arm/Group Description | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| Measure Participants | 10 | 11 | 27 | 27 |
| Basophils: Normal (at baseline) to Low (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Basophils: Normal (at baseline) to Normal (at post baseline) |
10
100%
|
11
100%
|
25
92.6%
|
27
100%
|
| Basophils: Normal (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Eosinophils: Normal (at baseline) to Low (at post baseline) |
0
0%
|
0
0%
|
0
0%
|
1
3.7%
|
| Eosinophils: Normal (at baseline) to Normal (at post baseline) |
7
70%
|
11
100%
|
25
92.6%
|
20
74.1%
|
| Eosinophils: Normal (at baseline) to High (at post baseline) |
2
20%
|
0
0%
|
1
3.7%
|
6
22.2%
|
| Eosinophils: Normal (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Eosinophils: High (at baseline) to Normal (at post baseline) |
1
10%
|
|||
| Hematocrit: Low (at baseline) to Low (at post baseline) |
2
20%
|
1
9.1%
|
8
29.6%
|
9
33.3%
|
| Hematocrit: Low (at baseline) to Normal (at post baseline) |
0
0%
|
1
9.1%
|
1
3.7%
|
0
0%
|
| Hematocrit: Low (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Hematocrit: Normal (at baseline) to Low (at post baseline) |
5
50%
|
4
36.4%
|
13
48.1%
|
12
44.4%
|
| Hematocrit: Normal (at baseline) to Normal (at post baseline) |
3
30%
|
4
36.4%
|
4
14.8%
|
6
22.2%
|
| Hematocrit: Normal (at baseline) to High & Low (at post baseline) |
0
0%
|
1
9.1%
|
0
0%
|
0
0%
|
| Monocytes: Normal (at baseline) to Low (at post baseline) |
1
10%
|
0
0%
|
1
3.7%
|
0
0%
|
| Monocytes: Normal (at baseline) to Normal (at post baseline) |
9
90%
|
7
63.6%
|
19
70.4%
|
20
74.1%
|
| Monocytes: Normal (at baseline) to High (at post baseline) |
0
0%
|
4
36.4%
|
6
22.2%
|
6
22.2%
|
| Monocytes: Normal (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Monocytes: High (at baseline) to Normal (at post baseline) |
1
10%
|
|||
| RBC: Low (at baseline) to Low (at post baseline) |
1
10%
|
1
9.1%
|
13
48.1%
|
6
22.2%
|
| RBC: Low (at baseline) to Normal (at post baseline) |
0
0%
|
1
9.1%
|
1
3.7%
|
1
3.7%
|
| RBC: Normal (at baseline) to Low (at post baseline) |
6
60%
|
5
45.5%
|
8
29.6%
|
10
37%
|
| RBC: Normal (at baseline) to Normal (at post baseline) |
2
20%
|
4
36.4%
|
3
11.1%
|
9
33.3%
|
| RBC: Normal (at baseline) to High (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| RBC: Normal (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| RBC: High (at baseline) to Low (at post baseline) |
0
0%
|
1
9.1%
|
||
| RBC: High (at baseline) to Normal (at post baseline) |
1
10%
|
0
0%
|
||
| Prothrombin Time: Normal (at baseline) to Normal (at post baseline) |
3
30%
|
3
27.3%
|
8
29.6%
|
8
29.6%
|
| Prothrombin Time: Normal (at baseline) to High (at post baseline) |
4
40%
|
4
36.4%
|
11
40.7%
|
9
33.3%
|
| Prothrombin Time: High (at baseline) to Normal (at post baseline) |
0
0%
|
1
9.1%
|
0
0%
|
0
0%
|
| Prothrombin Time: High (at baseline) to High (at post baseline) |
3
30%
|
3
27.3%
|
7
25.9%
|
9
33.3%
|
| Prothrombin Time: High (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Prothrombin Time: Missing (at baseline) to High (at post baseline) |
1
10%
|
| Title | Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on CTCAE v4.03: Chemistry |
|---|---|
| Description | Abnormalities: Albumin graded low, Alkaline phosphatase (ALP) graded high, Alanine aminotransferase (ALT) graded high, Aspartate aminotransferase (AST) graded high, Bilirubin graded high, Amylase graded high, Creatinine graded high, Corrected calcium graded high, Creatine Kinase (CK) graded high, Glucose graded high, Glucose graded low, Lipase graded high, Magnesium graded high, Magnesium graded low, Potassium graded high, Potassium graded low, Sodium graded high and Sodium graded low. Test abnormalities were graded by CTCAE v4.03 as Grade 1=mild; Grade 2=moderate; Grade 3/Grade 4=severe/life-threatening. A grade 0 was assigned for all non-missing values not graded as 1 or higher. If value was graded >=1 but falls within the normal range, the grade was reset to 0. Categories with at least 1 non-zero data values are reported. |
| Time Frame | Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety set included of all participants who received at least 1 dose of study drug. Here "Number Analyzed" signifies number of participants evaluable for specified rows. |
| Arm/Group Title | Phase 1b: Nivolumab+Binimetinib | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Phase 2: Nivolumab+Binimetinib | Phase 2: Nivolumab+Ipilimumab+Binimetinib |
|---|---|---|---|---|
| Arm/Group Description | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| Measure Participants | 10 | 11 | 27 | 27 |
| ALT- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) |
5
50%
|
5
45.5%
|
12
44.4%
|
12
44.4%
|
| ALT- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) |
3
30%
|
5
45.5%
|
7
25.9%
|
5
18.5%
|
| ALT- CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
1
3.7%
|
| ALT- CTCAE Graded High: Grade 0 (at baseline) to Grade 3 (at post baseline) |
0
0%
|
0
0%
|
0
0%
|
3
11.1%
|
| ALT- CTCAE Graded High: Grade 1 (at baseline) to Grade 0 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| ALT- CTCAE Graded High: Grade 1 (at baseline) to Grade 1 (at post baseline) |
1
10%
|
1
9.1%
|
3
11.1%
|
2
7.4%
|
| ALT- CTCAE Graded High: Grade 1 (at baseline) to Grade 2 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
2
7.4%
|
| ALT- CTCAE Graded High: Grade 1 (at baseline) to Grade 3 (at post baseline) |
0
0%
|
0
0%
|
0
0%
|
1
3.7%
|
| ALT- CTCAE Graded High: Grade 2 (at baseline) to Grade 2 (at post baseline) |
1
10%
|
1
9.1%
|
0
0%
|
|
| ALT- CTCAE Graded High: Grade 2 (at baseline) to Grade 3 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
|
| ALT- CTCAE Graded High: Grade 3 (at baseline) to Missing (at post baseline) |
1
10%
|
|||
| AST- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) |
3
30%
|
2
18.2%
|
8
29.6%
|
5
18.5%
|
| AST- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) |
5
50%
|
4
36.4%
|
11
40.7%
|
13
48.1%
|
| AST- CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) |
0
0%
|
1
9.1%
|
2
7.4%
|
2
7.4%
|
| AST- CTCAE Graded High: Grade 0 (at baseline) to Grade 3 (at post baseline) |
0
0%
|
0
0%
|
0
0%
|
2
7.4%
|
| AST- CTCAE Graded High: Grade 1 (at baseline) to Grade 1 (at post baseline) |
2
20%
|
4
36.4%
|
3
11.1%
|
1
3.7%
|
| AST- CTCAE Graded High: Grade 1 (at baseline) to Grade 2 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
3
11.1%
|
| AST- CTCAE Graded High: Grade 1 (at baseline) to Grade 3 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
1
3.7%
|
| AST- CTCAE Graded High: Grade 2 (at baseline) to Missing (at post baseline) |
1
10%
|
|||
| Albumin- CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) |
4
40%
|
2
18.2%
|
8
29.6%
|
8
29.6%
|
| Albumin- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) |
3
30%
|
2
18.2%
|
9
33.3%
|
11
40.7%
|
| Albumin- CTCAE Graded Low: Grade 0 (at baseline) to Grade 2 (at post baseline) |
3
30%
|
4
36.4%
|
7
25.9%
|
6
22.2%
|
| Albumin- CTCAE Graded Low: Grade 0 (at baseline) to Grade 3 (at post baseline) |
0
0%
|
0
0%
|
0
0%
|
1
3.7%
|
| Albumin- CTCAE Graded Low: Grade 0 (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Albumin- CTCAE Graded Low: Grade 1 (at baseline) to Grade 1 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
|
| Albumin- CTCAE Graded Low: Grade 1 (at baseline) to Grade 2 (at post baseline) |
2
20%
|
2
18.2%
|
0
0%
|
|
| Albumin- CTCAE Graded Low: Grade 2 (at baseline) to Grade 2 (at post baseline) |
1
10%
|
|||
| Alkaline phosphatase- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) |
2
20%
|
2
18.2%
|
7
25.9%
|
6
22.2%
|
| Alkaline phosphatase- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) |
3
30%
|
1
9.1%
|
8
29.6%
|
5
18.5%
|
| Alkaline phosphatase- CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) |
0
0%
|
1
9.1%
|
0
0%
|
1
3.7%
|
| Alkaline phosphatase- CTCAE Graded High: Grade 1 (at baseline) to Grade 1 (at post baseline) |
1
10%
|
0
0%
|
5
18.5%
|
7
25.9%
|
| Alkaline phosphatase- CTCAE Graded High: Grade 1 (at baseline) to Grade 2 (at post baseline) |
2
20%
|
4
36.4%
|
3
11.1%
|
3
11.1%
|
| Alkaline phosphatase- CTCAE Graded High: Grade 1 (at baseline) to Grade 3 (at post baseline) |
1
10%
|
0
0%
|
1
3.7%
|
1
3.7%
|
| Alkaline phosphatase- CTCAE Graded High: Grade 2 (at baseline) to Grade 2 (at post baseline) |
0
0%
|
1
9.1%
|
0
0%
|
0
0%
|
| Alkaline phosphatase- CTCAE Graded High: Grade 2 (at baseline) to Grade 3 (at post baseline) |
1
10%
|
0
0%
|
2
7.4%
|
2
7.4%
|
| Alkaline phosphatase- CTCAE Graded High: Grade 3 (at baseline) to Grade 3 (at post baseline) |
2
20%
|
0
0%
|
2
7.4%
|
|
| Alkaline phosphatase- CTCAE Graded High: Grade 3 (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Amylase- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) |
8
80%
|
7
63.6%
|
18
66.7%
|
20
74.1%
|
| Amylase- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) |
1
10%
|
2
18.2%
|
5
18.5%
|
2
7.4%
|
| Amylase- CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
2
7.4%
|
| Amylase- CTCAE Graded High: Grade 0 (at baseline) to Grade 3 (at post baseline) |
0
0%
|
1
9.1%
|
2
7.4%
|
2
7.4%
|
| Amylase- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) |
0
0%
|
1
9.1%
|
1
3.7%
|
0
0%
|
| Amylase- CTCAE Graded High: Grade 1 (at baseline) to Grade 2 (at post baseline) |
1
10%
|
|||
| Amylase- CTCAE Graded High: Grade 2 (at baseline) to Grade 4 (at post baseline) |
1
10%
|
|||
| Bilirubin- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) |
10
100%
|
9
81.8%
|
25
92.6%
|
24
88.9%
|
| Bilirubin- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
2
7.4%
|
| Bilirubin- CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) |
0
0%
|
1
9.1%
|
0
0%
|
1
3.7%
|
| Bilirubin- CTCAE Graded High: Grade 1 (at baseline) to Grade 2 (at post baseline) |
1
10%
|
|||
| Bilirubin- CTCAE Graded High: Grade 4 (at baseline) to Missing (at post baseline) |
1
10%
|
|||
| Corrected Calcium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) |
7
70%
|
11
100%
|
24
88.9%
|
25
92.6%
|
| Corrected Calcium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) |
3
30%
|
0
0%
|
2
7.4%
|
1
3.7%
|
| Corrected Calcium- CTCAE Graded Low: Grade 0 (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Corrected Calcium- CTCAE Graded Low: Grade 1 (at baseline) to Grade 0 (at post baseline) |
1
10%
|
|||
| Corrected Calcium- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) |
10
100%
|
11
100%
|
25
92.6%
|
25
92.6%
|
| Corrected Calcium- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
1
3.7%
|
| Corrected Calcium- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Corrected Calcium- CTCAE Graded High: Grade 1 (at baseline) to Grade 0 (at post baseline) |
1
10%
|
|||
| Creatine kinase- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) |
1
10%
|
3
27.3%
|
3
11.1%
|
7
25.9%
|
| Creatine kinase- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) |
3
30%
|
4
36.4%
|
11
40.7%
|
7
25.9%
|
| Creatine kinase- CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) |
4
40%
|
2
18.2%
|
6
22.2%
|
8
29.6%
|
| Creatine kinase- CTCAE Graded High: Grade 0 (at baseline) to Grade 3 (at post baseline) |
1
10%
|
1
9.1%
|
5
18.5%
|
1
3.7%
|
| Creatine kinase- CTCAE Graded High: Grade 0 (at baseline) to Grade 4 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Creatine kinase- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Creatine kinase- CTCAE Graded High: Grade 1 (at baseline) to Grade 2 (at post baseline) |
0
0%
|
1
9.1%
|
1
3.7%
|
|
| Creatine kinase- CTCAE Graded High: Grade 1 (at baseline) to Grade 3 (at post baseline) |
1
10%
|
0
0%
|
1
3.7%
|
|
| Creatine kinase- CTCAE Graded High: Grade 1 (at baseline) to Grade 4 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
|
| Creatine kinase - CTCAE Graded High: Missing (at baseline) to Grade 1 (at post baseline) |
1
10%
|
|||
| Creatinine- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) |
1
10%
|
2
18.2%
|
6
22.2%
|
7
25.9%
|
| Creatinine- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) |
7
70%
|
7
63.6%
|
14
51.9%
|
18
66.7%
|
| Creatinine- CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) |
2
20%
|
2
18.2%
|
5
18.5%
|
2
7.4%
|
| Creatinine- CTCAE Graded High: Grade 0 (at baseline) to Grade 4 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Creatinine- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Glucose- CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) |
10
100%
|
10
90.9%
|
23
85.2%
|
26
96.3%
|
| Glucose- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) |
0
0%
|
1
9.1%
|
1
3.7%
|
0
0%
|
| Glucose- CTCAE Graded Low: Grade 0 (at baseline) to Grade 2 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Glucose- CTCAE Graded Low: Grade 0 (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Glucose- CTCAE Graded Low: Grade 1 (at baseline) to Grade 0 (at post baseline) |
0
0%
|
1
9.1%
|
||
| Glucose- CTCAE Graded Low: Grade 1 (at baseline) to Grade 1 (at post baseline) |
1
10%
|
0
0%
|
||
| Glucose- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) |
7
70%
|
6
54.5%
|
18
66.7%
|
14
51.9%
|
| Glucose- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) |
0
0%
|
1
9.1%
|
1
3.7%
|
1
3.7%
|
| Glucose - CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) |
1
10%
|
1
9.1%
|
0
0%
|
1
3.7%
|
| Glucose- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) |
1
10%
|
2
18.2%
|
5
18.5%
|
5
18.5%
|
| Glucose- CTCAE Graded High: Grade 1 (at baseline) to Grade 0 (at post baseline) |
1
10%
|
0
0%
|
||
| Glucose - CTCAE Graded High: Grade 1 (at baseline) to Grade 2 (at post baseline) |
0
0%
|
1
9.1%
|
||
| Glucose- CTCAE Graded High: Grade 3 (at baseline) to Grade 2 (at post baseline) |
1
10%
|
0
0%
|
||
| Glucose- CTCAE Graded High: Grade 3 (at baseline) to Grade 3 (at post baseline) |
0
0%
|
1
9.1%
|
||
| Glucose- CTCAE Graded High: Grade 3 (at baseline) to Missing (at post baseline) |
0
0%
|
1
9.1%
|
||
| Glucose- CTCAE Graded High: Missing (at baseline) to Grade 0 (at post baseline) |
0
0%
|
0
0%
|
0
0%
|
1
3.7%
|
| Glucose- CTCAE Graded High: Missing (at baseline) to Grade 3 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Glucose- CTCAE Graded High: Missing (at baseline) to Missing (at post baseline) |
1
10%
|
1
9.1%
|
0
0%
|
2
7.4%
|
| Lipase- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) |
5
50%
|
6
54.5%
|
17
63%
|
15
55.6%
|
| Lipase- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) |
2
20%
|
2
18.2%
|
2
7.4%
|
4
14.8%
|
| Lipase- CTCAE Graded High: Grade 0 (at baseline) to Grade 2 (at post baseline) |
1
10%
|
1
9.1%
|
1
3.7%
|
0
0%
|
| Lipase- CTCAE Graded High: Grade 0 (at baseline) to Grade 3 (at post baseline) |
1
10%
|
0
0%
|
4
14.8%
|
3
11.1%
|
| Lipase- CTCAE Graded High: Grade 0 (at baseline) to Grade 4 (at post baseline) |
0
0%
|
0
0%
|
0
0%
|
1
3.7%
|
| Lipase- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) |
0
0%
|
1
9.1%
|
1
3.7%
|
0
0%
|
| Lipase- CTCAE Graded High: Grade 1 (at baseline) to Grade 0 (at post baseline) |
1
10%
|
0
0%
|
1
3.7%
|
0
0%
|
| Lipase- CTCAE Graded High: Grade 1 (at baseline) to Grade 1 (at post baseline) |
0
0%
|
1
9.1%
|
1
3.7%
|
2
7.4%
|
| Lipase- CTCAE Graded High: Grade 1 (at baseline) to Grade 3 (at post baseline) |
0
0%
|
0
0%
|
0
0%
|
1
3.7%
|
| Lipase- CTCAE Graded High: Grade 4 (at baseline) to Grade 4 (at post baseline) |
1
10%
|
|||
| Magnesium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) |
8
80%
|
10
90.9%
|
22
81.5%
|
24
88.9%
|
| Magnesium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) |
1
10%
|
1
9.1%
|
3
11.1%
|
2
7.4%
|
| Magnesium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 2 (at post baseline) |
0
0%
|
0
0%
|
0
0%
|
1
3.7%
|
| Magnesium- CTCAE Graded Low: Grade 0 (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Magnesium- CTCAE Graded Low: Grade 1 (at baseline) to Grade 2 (at post baseline) |
1
10%
|
|||
| Magnesium- CTCAE Graded Low: Grade 2 (at baseline) to Grade 3 (at post baseline) |
1
10%
|
|||
| Magnesium- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) |
10
100%
|
11
100%
|
26
96.3%
|
27
100%
|
| Magnesium- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Potassium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) |
7
70%
|
9
81.8%
|
20
74.1%
|
23
85.2%
|
| Potassium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) |
3
30%
|
2
18.2%
|
3
11.1%
|
4
14.8%
|
| Potassium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 3 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Potassium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 4 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Potassium- CTCAE Graded Low: Grade 0 (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Potassium- CTCAE Graded Low: Grade 3 (at baseline) to Grade 3 (at post baseline) |
1
10%
|
|||
| Potassium- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) |
9
90%
|
10
90.9%
|
23
85.2%
|
23
85.2%
|
| Potassium- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) |
1
10%
|
1
9.1%
|
2
7.4%
|
4
14.8%
|
| Potassium- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Potassium- CTCAE Graded High: Grade 1 (at baseline) to Grade 0 (at post baseline) |
1
10%
|
|||
| Sodium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 0 (at post baseline) |
9
90%
|
7
63.6%
|
19
70.4%
|
23
85.2%
|
| Sodium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 1 (at post baseline) |
1
10%
|
3
27.3%
|
3
11.1%
|
1
3.7%
|
| Sodium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 3 (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
2
7.4%
|
| Sodium- CTCAE Graded Low: Grade 0 (at baseline) to Grade 4 (at post baseline) |
0
0%
|
0
0%
|
2
7.4%
|
1
3.7%
|
| Sodium- CTCAE Graded Low: Grade 1 (at baseline) to Grade 1 (at post baseline) |
1
10%
|
|||
| Sodium- CTCAE Graded Low: Grade 1 (at baseline) to Missing (at post baseline) |
1
10%
|
|||
| Sodium- CTCAE Graded Low: Grade 3 (at baseline) to Grade 3 (at post baseline) |
1
10%
|
|||
| Sodium- CTCAE Graded High: Grade 0 (at baseline) to Grade 0 (at post baseline) |
10
100%
|
11
100%
|
23
85.2%
|
22
81.5%
|
| Sodium- CTCAE Graded High: Grade 0 (at baseline) to Grade 1 (at post baseline) |
0
0%
|
0
0%
|
3
11.1%
|
5
18.5%
|
| Sodium- CTCAE Graded High: Grade 0 (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Title | Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on Normal Range: Chemistry and Thyroid Function |
|---|---|
| Description | Chemistry laboratory parameters: Blood urea nitrogen (BUN), Total protein, Chloride, Cancer antigen 19-9 (CA 19-9), Brain natriuretic peptide (BNP), Bicarbonate, Direct bilirubin, Carcinoembryonic antigen (CEA), Lactate dehydrogenase (LDH), Uric acid, Troponin I. Thyroid panel laboratory parameters: Thyroid-stimulating hormone (TSH), Free triiodothyronine (T3), Free thyroxine (T4). Laboratory values were as per laboratory normal ranges. Values above range were reported as high and values below range as low. Shift in chemistry and thyroid panel severity from baseline grade low, normal, high and missing to the post baseline grades as low, normal, high and missing are reported in this outcome measure. Categories with at least 1 non-zero data values are reported. |
| Time Frame | Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety set included of all participants who received at least 1 dose of study drug. Here "Number Analyzed" signifies number of participants evaluable for specified rows. |
| Arm/Group Title | Phase 1b: Nivolumab+Binimetinib | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Phase 2: Nivolumab+Binimetinib | Phase 2: Nivolumab+Ipilimumab+Binimetinib |
|---|---|---|---|---|
| Arm/Group Description | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| Measure Participants | 10 | 11 | 27 | 27 |
| BNP: Normal (at baseline) to Normal (at post baseline) |
8
80%
|
6
54.5%
|
24
88.9%
|
22
81.5%
|
| BNP: Normal (at baseline) to High (at post baseline) |
1
10%
|
3
27.3%
|
2
7.4%
|
3
11.1%
|
| BNP: Normal (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| BNP: High (at baseline) to Normal (at post baseline) |
0
0%
|
2
18.2%
|
0
0%
|
|
| BNP: High (at baseline) to High (at post baseline) |
1
10%
|
0
0%
|
2
7.4%
|
|
| BUN: Normal (at baseline) to Normal (at post baseline) |
4
40%
|
3
27.3%
|
15
55.6%
|
14
51.9%
|
| BUN (mmol/L): Normal (at baseline) to High (at post baseline) |
3
30%
|
5
45.5%
|
9
33.3%
|
7
25.9%
|
| BUN: Normal (at baseline) to Missing (at post baseline) |
0
0%
|
1
9.1%
|
1
3.7%
|
0
0%
|
| BUN: High (at baseline) to Normal (at post baseline) |
0
0%
|
0
0%
|
2
7.4%
|
3
11.1%
|
| BUN: High (at baseline) to High (at post baseline) |
3
30%
|
2
18.2%
|
0
0%
|
3
11.1%
|
| Bicarbonate: Low (at baseline) to Normal (at post baseline) |
1
10%
|
0
0%
|
3
11.1%
|
|
| Bicarbonate: Low (at baseline) to High (at post baseline) |
1
10%
|
1
9.1%
|
0
0%
|
|
| Bicarbonate: Normal (at baseline) to Low (at post baseline) |
2
20%
|
1
9.1%
|
6
22.2%
|
9
33.3%
|
| Bicarbonate: Normal (at baseline) to Normal (at post baseline) |
7
70%
|
6
54.5%
|
18
66.7%
|
11
40.7%
|
| Bicarbonate: Normal (at baseline) to High (at post baseline) |
1
10%
|
2
18.2%
|
1
3.7%
|
3
11.1%
|
| Bicarbonate: Normal (at baseline) to High and Low (at post baseline) |
0
0%
|
0
0%
|
0
0%
|
1
3.7%
|
| Bicarbonate: Normal (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| CA 19-9: Normal (at baseline) to Normal (at post baseline) |
3
30%
|
3
27.3%
|
6
22.2%
|
7
25.9%
|
| CA 19-9: Normal (at baseline) to High (at post baseline) |
0
0%
|
0
0%
|
2
7.4%
|
1
3.7%
|
| CA 19-9: Normal (at baseline) to Missing (at post baseline) |
0
0%
|
1
9.1%
|
0
0%
|
1
3.7%
|
| CA 19-9: High (at baseline) to Normal (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
1
3.7%
|
| CA 19-9: High (at baseline) to High (at post baseline) |
7
70%
|
6
54.5%
|
16
59.3%
|
16
59.3%
|
| CA 19-9: High (at baseline) to Missing (at post baseline) |
0
0%
|
1
9.1%
|
2
7.4%
|
1
3.7%
|
| CEA: Normal (at baseline) to Normal (at post baseline) |
1
10%
|
1
9.1%
|
3
11.1%
|
|
| CEA: Normal (at baseline) to High (at post baseline) |
0
0%
|
2
18.2%
|
2
7.4%
|
|
| CEA: Normal (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
|
| CEA: High (at baseline) to Normal (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| CEA: High (at baseline) to High (at post baseline) |
9
90%
|
9
81.8%
|
20
74.1%
|
20
74.1%
|
| CEA: High (at baseline) to Missing (at post baseline) |
0
0%
|
2
18.2%
|
3
11.1%
|
1
3.7%
|
| Chloride: Low (at baseline) to Low (at post baseline) |
1
10%
|
1
9.1%
|
1
3.7%
|
|
| Chloride: Low (at baseline) to Missing (at post baseline) |
0
0%
|
1
9.1%
|
0
0%
|
|
| Chloride: Normal (at baseline) to Low (at post baseline) |
2
20%
|
2
18.2%
|
8
29.6%
|
3
11.1%
|
| Chloride: Normal (at baseline) to Normal (at post baseline) |
8
80%
|
7
63.6%
|
15
55.6%
|
22
81.5%
|
| Chloride: Normal (at baseline) to High (at post baseline) |
0
0%
|
0
0%
|
2
7.4%
|
1
3.7%
|
| Chloride: Normal (at baseline) to High & Low (at post baseline) |
0
0%
|
1
9.1%
|
0
0%
|
0
0%
|
| Free T3: Low (at baseline) to Low (at post baseline) |
0
0%
|
1
9.1%
|
||
| Free T3: Low (at baseline) to Missing (at post baseline) |
1
10%
|
1
9.1%
|
||
| Free T3: Normal (at baseline) to Low (at post baseline) |
3
30%
|
5
45.5%
|
8
29.6%
|
7
25.9%
|
| Free T3: Normal (at baseline) to Normal (at post baseline) |
7
70%
|
5
45.5%
|
15
55.6%
|
15
55.6%
|
| Free T3: Normal (at baseline) to High and Low (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Free T3: Normal (at baseline) to Missing (at post baseline) |
0
0%
|
1
9.1%
|
2
7.4%
|
1
3.7%
|
| Free T3: High (at baseline) to High (at post baseline) |
2
20%
|
|||
| Free T4: Low (at baseline) to Low (at post baseline) |
0
0%
|
1
9.1%
|
||
| Free T4: Low (at baseline) to Normal (at post baseline) |
1
10%
|
0
0%
|
||
| Free T4: Normal (at baseline) to Low (at post baseline) |
0
0%
|
1
9.1%
|
2
7.4%
|
3
11.1%
|
| Free T4: Normal (at baseline) to Normal (at post baseline) |
10
100%
|
8
72.7%
|
17
63%
|
17
63%
|
| Free T4: Normal (at baseline) to High (at post baseline) |
0
0%
|
0
0%
|
3
11.1%
|
1
3.7%
|
| Free T4: Normal (at baseline) to High and Low (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
1
3.7%
|
| Free T4: Normal (at baseline) to Missing (at post baseline) |
0
0%
|
1
9.1%
|
3
11.1%
|
2
7.4%
|
| Free T4: High (at baseline) to Low (at post baseline) |
0
0%
|
1
9.1%
|
||
| Free T4: High (at baseline) to Normal (at post baseline) |
1
10%
|
1
9.1%
|
||
| LDH: Low (at baseline) to Low (at post baseline) |
1
10%
|
|||
| LDH: Normal (at baseline) to Normal (at post baseline) |
1
10%
|
1
9.1%
|
6
22.2%
|
5
18.5%
|
| LDH: Normal (at baseline) to High (at post baseline) |
5
50%
|
4
36.4%
|
14
51.9%
|
10
37%
|
| LDH: High (at baseline) to Normal (at post baseline) |
0
0%
|
0
0%
|
0
0%
|
1
3.7%
|
| LDH: High (at baseline) to High (at post baseline) |
3
30%
|
6
54.5%
|
6
22.2%
|
11
40.7%
|
| LDH: High (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Protein: Low (at baseline) to Low (at post baseline) |
1
10%
|
|||
| Protein: Normal (at baseline) to Low (at post baseline) |
5
50%
|
6
54.5%
|
11
40.7%
|
11
40.7%
|
| Protein: Normal (at baseline) to Normal (at post baseline) |
5
50%
|
4
36.4%
|
12
44.4%
|
14
51.9%
|
| Protein: Normal (at baseline) to High (at post baseline) |
0
0%
|
0
0%
|
0
0%
|
2
7.4%
|
| Protein: Normal (at baseline) to High and Low (at post baseline) |
0
0%
|
0
0%
|
3
11.1%
|
0
0%
|
| Protein: Normal (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| TSH: Low (at baseline) to Low (at post baseline) |
1
10%
|
|||
| TSH: Normal (at baseline) to Low (at post baseline) |
0
0%
|
0
0%
|
2
7.4%
|
3
11.1%
|
| TSH: Normal (at baseline) to Normal (at post baseline) |
8
80%
|
7
63.6%
|
14
51.9%
|
20
74.1%
|
| TSH: Normal (at baseline) to High (at post baseline) |
1
10%
|
0
0%
|
3
11.1%
|
1
3.7%
|
| TSH: Normal (at baseline) to High and Low (at post baseline) |
0
0%
|
0
0%
|
2
7.4%
|
0
0%
|
| TSH: Normal (at baseline) to Missing (at post baseline) |
0
0%
|
0
0%
|
3
11.1%
|
2
7.4%
|
| TSH: High (at baseline) to Normal (at post baseline) |
0
0%
|
2
18.2%
|
2
7.4%
|
|
| TSH: High (at baseline) to High (at post baseline) |
1
10%
|
1
9.1%
|
1
3.7%
|
|
| TSH: High (at baseline) to Missing (at post baseline) |
0
0%
|
1
9.1%
|
0
0%
|
|
| Troponin I: Normal (at baseline) to Normal (at post baseline) |
2
20%
|
11
100%
|
10
37%
|
|
| Troponin I: Normal (at baseline) to High (at post baseline) |
0
0%
|
1
9.1%
|
2
7.4%
|
|
| Troponin I: Normal (at baseline) to Missing (at post baseline) |
0
0%
|
14
127.3%
|
14
51.9%
|
|
| Troponin I: Missing (at baseline) to Normal (at post baseline) |
4
40%
|
3
27.3%
|
1
3.7%
|
|
| Troponin I: Missing (at baseline) to High (at post baseline) |
1
10%
|
0
0%
|
0
0%
|
|
| Uric acid: Low (at baseline) to Low (at post baseline) |
0
0%
|
0
0%
|
2
7.4%
|
|
| Uric acid: Low (at baseline) to Normal (at post baseline) |
1
10%
|
0
0%
|
1
3.7%
|
|
| Uric acid: Low (at baseline) to Missing (at post baseline) |
0
0%
|
1
9.1%
|
0
0%
|
|
| Uric acid: Normal (at baseline) to Low (at post baseline) |
1
10%
|
2
18.2%
|
4
14.8%
|
4
14.8%
|
| Uric acid: Normal (at baseline) to Normal (at post baseline) |
8
80%
|
5
45.5%
|
15
55.6%
|
16
59.3%
|
| Uric acid: Normal (at baseline) to High (at post baseline) |
0
0%
|
2
18.2%
|
4
14.8%
|
1
3.7%
|
| Uric acid: High (at baseline) to Normal (at post baseline) |
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
| Uric acid: High (at baseline) to High (at post baseline) |
1
10%
|
1
9.1%
|
2
7.4%
|
3
11.1%
|
| Title | Number of Participants With Abnormal Hepatic Laboratory Values |
|---|---|
| Description | Criteria for abnormal hepatic laboratory parameters: Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT): >3* upper limit of normal (ULN), >5*ULN, >8*ULN, >10*ULN, >20*ULN; Total bilirubin (TBL) >1.5*ULN, >2*ULN; Alkaline phosphatase (ALP) >2*ULN, >3*ULN. Categories with at least 1 non-zero data values are reported. |
| Time Frame | Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety set included of all participants who received at least 1 dose of study drug. Here "Number Analyzed" signifies number of participants evaluable for specified rows. |
| Arm/Group Title | Phase 1b: Nivolumab+Binimetinib | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Phase 2: Nivolumab+Binimetinib | Phase 2: Nivolumab+Ipilimumab+Binimetinib |
|---|---|---|---|---|
| Arm/Group Description | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| Measure Participants | 10 | 11 | 27 | 27 |
| ALT: >3 ULN |
0
0%
|
0
0%
|
2
7.4%
|
7
25.9%
|
| ALT: >5 ULN |
0
0%
|
0
0%
|
0
0%
|
5
18.5%
|
| ALT: >8 ULN |
0
0%
|
0
0%
|
0
0%
|
1
3.7%
|
| AST: >3 ULN |
0
0%
|
1
9.1%
|
4
14.8%
|
8
29.6%
|
| AST: >5 ULN |
0
0%
|
0
0%
|
1
3.7%
|
3
11.1%
|
| AST: >8 ULN |
0
0%
|
0
0%
|
1
3.7%
|
1
3.7%
|
| ALT or AST: >3 ULN |
0
0%
|
1
9.1%
|
3
11.1%
|
7
25.9%
|
| ALT or AST: >5 ULN |
0
0%
|
0
0%
|
1
3.7%
|
4
14.8%
|
| ALT or AST: >8 ULN |
0
0%
|
0
0%
|
1
3.7%
|
1
3.7%
|
| Total bilirubin: >1.5 ULN |
0
0%
|
2
18.2%
|
0
0%
|
1
3.7%
|
| Alkaline phosphatase: >2 ULN |
3
30%
|
3
27.3%
|
4
14.8%
|
8
29.6%
|
| Alkaline phosphatase: >3 ULN |
4
40%
|
4
36.4%
|
2
7.4%
|
4
14.8%
|
| Title | Concentration Versus Time Summary of Plasma Concentration of Binimetinib |
|---|---|
| Description | |
| Time Frame | 1.5 hours post dose of binimetinib on Day 1, 15 of Cycle 1; pre dose of binimetinib on Day 15 of Cycle 1, 2, 3, 4, 5 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacokinetic analysis set included of all participants who received at least 1 dose of binimetinib and have at least one evaluable bioanalytical result. Here "Number Analyzed" signifies number of participants evaluable for specified rows. |
| Arm/Group Title | Phase 1b: Nivolumab+Binimetinib | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Phase 2: Nivolumab+Binimetinib | Phase 2: Nivolumab+Ipilimumab+Binimetinib |
|---|---|---|---|---|
| Arm/Group Description | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| Measure Participants | 10 | 11 | 26 | 27 |
| Cycle 1 Day 1: 1.5 Hours post dose |
228
(152.2)
|
163
(129.6)
|
261
(90.9)
|
217
(134.5)
|
| Cycle 1 Day 15: pre dose |
135
(60.9)
|
125
(103.9)
|
77.0
(141.2)
|
81.8
(143.6)
|
| Cycle 1 Day 15: 1.5 Hours post dose |
542
(57.6)
|
414
(24.5)
|
294
(84.4)
|
324
(83.3)
|
| Cycle 2 Day 15: pre dose |
108
(52.9)
|
NA
(NA)
|
88.5
(111.3)
|
120
(77.7)
|
| Cycle 3 Day 15: pre dose |
140
(42.0)
|
NA
(NA)
|
NA
(NA)
|
89.2
(183.4)
|
| Cycle 4 Day 15: pre dose |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 5 Day 15: pre dose |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
Adverse Events
| Time Frame | All-Cause Mortality: From start of the treatment up to 150 days after last dose (Phase 1b: maximum up to 13 months approximately and Phase 2: maximum up to 30 months approximately); TEAEs (including serious and other AEs): From start of the treatment up to 30 days after last dose (Phase 1b: maximum up to 9 months approximately and Phase 2: maximum up to 26 months approximately) | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety set was evaluated. Both TEAE and treatment related AEs were monitored. | |||||||
| Arm/Group Title | Phase 1b: Nivolumab+Binimetinib | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Phase 2: Nivolumab+Binimetinib | Phase 2: Nivolumab+Ipilimumab+Binimetinib | ||||
| Arm/Group Description | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. | ||||
All Cause Mortality |
||||||||
| Phase 1b: Nivolumab+Binimetinib | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Phase 2: Nivolumab+Binimetinib | Phase 2: Nivolumab+Ipilimumab+Binimetinib | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/10 (80%) | 8/11 (72.7%) | 20/27 (74.1%) | 21/27 (77.8%) | ||||
Serious Adverse Events |
||||||||
| Phase 1b: Nivolumab+Binimetinib | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Phase 2: Nivolumab+Binimetinib | Phase 2: Nivolumab+Ipilimumab+Binimetinib | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/10 (50%) | 6/11 (54.5%) | 12/27 (44.4%) | 11/27 (40.7%) | ||||
| Cardiac disorders | ||||||||
| Myocarditis | 0/10 (0%) | 1/11 (9.1%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Pericardial effusion | 0/10 (0%) | 0/11 (0%) | 2/27 (7.4%) | 0/27 (0%) | ||||
| Acute coronary syndrome | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Cardiac failure | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Endocrine disorders | ||||||||
| Hypophysitis | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Gastrointestinal disorders | ||||||||
| Intestinal obstruction | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 1/27 (3.7%) | ||||
| Abdominal pain | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Colitis | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Constipation | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Diarrhoea | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Ileus | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Nausea | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Pancreatitis | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Small intestinal obstruction | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Vomiting | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| General disorders | ||||||||
| Pyrexia | 1/10 (10%) | 0/11 (0%) | 1/27 (3.7%) | 1/27 (3.7%) | ||||
| Asthenia | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Localised oedema | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Pain | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Hepatitis | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Infections and infestations | ||||||||
| Pneumonia | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 2/27 (7.4%) | ||||
| Abdominal infection | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Bacterial sepsis | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Candida infection | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Cellulitis | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Empyema | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Infected seroma | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Klebsiella bacteraemia | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Lung infection | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Periorbital cellulitis | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Pneumocystis jirovecii pneumonia | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Pneumonia bacterial | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Fall | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Hip fracture | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Infusion related reaction | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Investigations | ||||||||
| Aspartate aminotransferase increased | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Blood creatine phosphokinase increased | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Transaminases increased | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Hyponatraemia | 0/10 (0%) | 1/11 (9.1%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Myositis | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Pain in extremity | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Tumour associated fever | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Nervous system disorders | ||||||||
| Ataxia | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Nephritis | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Renal colic | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Pleural effusion | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 2/27 (7.4%) | ||||
| Pneumonitis | 0/10 (0%) | 2/11 (18.2%) | 0/27 (0%) | 0/27 (0%) | ||||
| Hypoxia | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Pleurisy | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Pulmonary oedema | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Dermatitis acneiform | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Skin reaction | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Vascular disorders | ||||||||
| Superior vena cava syndrome | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Phase 1b: Nivolumab+Binimetinib | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Phase 2: Nivolumab+Binimetinib | Phase 2: Nivolumab+Ipilimumab+Binimetinib | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/10 (100%) | 11/11 (100%) | 27/27 (100%) | 27/27 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/10 (0%) | 1/11 (9.1%) | 7/27 (25.9%) | 4/27 (14.8%) | ||||
| Leukopenia | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Thrombocytopenia | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Cardiac disorders | ||||||||
| Cardiac failure | 0/10 (0%) | 0/11 (0%) | 2/27 (7.4%) | 1/27 (3.7%) | ||||
| Ventricular hypokinesia | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Endocrine disorders | ||||||||
| Hypothyroidism | 1/10 (10%) | 1/11 (9.1%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Eye disorders | ||||||||
| Visual impairment | 2/10 (20%) | 1/11 (9.1%) | 0/27 (0%) | 3/27 (11.1%) | ||||
| Periorbital oedema | 1/10 (10%) | 0/11 (0%) | 3/27 (11.1%) | 1/27 (3.7%) | ||||
| Vision blurred | 1/10 (10%) | 1/11 (9.1%) | 1/27 (3.7%) | 1/27 (3.7%) | ||||
| Eyelid oedema | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 2/27 (7.4%) | ||||
| Subretinal fluid | 0/10 (0%) | 0/11 (0%) | 2/27 (7.4%) | 1/27 (3.7%) | ||||
| Macular oedema | 0/10 (0%) | 0/11 (0%) | 2/27 (7.4%) | 0/27 (0%) | ||||
| Photopsia | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Retinopathy | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 2/27 (7.4%) | ||||
| Dry age-related macular degeneration | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Eye oedema | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Vitreous detachment | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Diarrhoea | 6/10 (60%) | 4/11 (36.4%) | 13/27 (48.1%) | 15/27 (55.6%) | ||||
| Nausea | 5/10 (50%) | 2/11 (18.2%) | 12/27 (44.4%) | 11/27 (40.7%) | ||||
| Vomiting | 2/10 (20%) | 8/11 (72.7%) | 7/27 (25.9%) | 10/27 (37%) | ||||
| Constipation | 2/10 (20%) | 3/11 (27.3%) | 9/27 (33.3%) | 6/27 (22.2%) | ||||
| Abdominal pain | 1/10 (10%) | 0/11 (0%) | 5/27 (18.5%) | 5/27 (18.5%) | ||||
| Dry mouth | 0/10 (0%) | 1/11 (9.1%) | 3/27 (11.1%) | 5/27 (18.5%) | ||||
| Stomatitis | 1/10 (10%) | 2/11 (18.2%) | 3/27 (11.1%) | 3/27 (11.1%) | ||||
| Abdominal distension | 0/10 (0%) | 1/11 (9.1%) | 3/27 (11.1%) | 3/27 (11.1%) | ||||
| Dyspepsia | 1/10 (10%) | 1/11 (9.1%) | 1/27 (3.7%) | 3/27 (11.1%) | ||||
| Gastrooesophageal reflux disease | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 5/27 (18.5%) | ||||
| Ascites | 0/10 (0%) | 0/11 (0%) | 4/27 (14.8%) | 0/27 (0%) | ||||
| Abdominal discomfort | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 2/27 (7.4%) | ||||
| Abdominal pain upper | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 2/27 (7.4%) | ||||
| Abdominal pain lower | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 2/27 (7.4%) | ||||
| Haemorrhoids | 0/10 (0%) | 1/11 (9.1%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Pancreatitis | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 2/27 (7.4%) | ||||
| Proctalgia | 0/10 (0%) | 0/11 (0%) | 2/27 (7.4%) | 0/27 (0%) | ||||
| Colitis | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Glossitis | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Lower gastrointestinal haemorrhage | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Mesenteric arterial occlusion | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Small intestinal obstruction | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| General disorders | ||||||||
| Fatigue | 4/10 (40%) | 6/11 (54.5%) | 11/27 (40.7%) | 11/27 (40.7%) | ||||
| Oedema peripheral | 5/10 (50%) | 5/11 (45.5%) | 8/27 (29.6%) | 11/27 (40.7%) | ||||
| Pyrexia | 3/10 (30%) | 3/11 (27.3%) | 8/27 (29.6%) | 14/27 (51.9%) | ||||
| Asthenia | 3/10 (30%) | 1/11 (9.1%) | 7/27 (25.9%) | 9/27 (33.3%) | ||||
| Chills | 1/10 (10%) | 1/11 (9.1%) | 4/27 (14.8%) | 4/27 (14.8%) | ||||
| Face oedema | 0/10 (0%) | 1/11 (9.1%) | 4/27 (14.8%) | 1/27 (3.7%) | ||||
| Localised oedema | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 3/27 (11.1%) | ||||
| Influenza like illness | 0/10 (0%) | 2/11 (18.2%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Infections and infestations | ||||||||
| Paronychia | 1/10 (10%) | 1/11 (9.1%) | 3/27 (11.1%) | 3/27 (11.1%) | ||||
| Rash pustular | 1/10 (10%) | 1/11 (9.1%) | 2/27 (7.4%) | 3/27 (11.1%) | ||||
| Urinary tract infection | 0/10 (0%) | 1/11 (9.1%) | 2/27 (7.4%) | 0/27 (0%) | ||||
| Bronchitis | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Folliculitis | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 2/27 (7.4%) | ||||
| Oral herpes | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Conjunctivitis | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Pneumonia | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Staphylococcal bacteraemia | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Abdominal injury | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 2/27 (7.4%) | ||||
| Fall | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Skin abrasion | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Laceration | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Scratch | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Investigations | ||||||||
| Blood creatine phosphokinase increased | 5/10 (50%) | 3/11 (27.3%) | 14/27 (51.9%) | 13/27 (48.1%) | ||||
| Aspartate aminotransferase increased | 0/10 (0%) | 3/11 (27.3%) | 2/27 (7.4%) | 9/27 (33.3%) | ||||
| Alanine aminotransferase increased | 0/10 (0%) | 2/11 (18.2%) | 2/27 (7.4%) | 8/27 (29.6%) | ||||
| Ejection fraction decreased | 1/10 (10%) | 0/11 (0%) | 4/27 (14.8%) | 7/27 (25.9%) | ||||
| Blood alkaline phosphatase increased | 1/10 (10%) | 0/11 (0%) | 1/27 (3.7%) | 5/27 (18.5%) | ||||
| Amylase increased | 0/10 (0%) | 0/11 (0%) | 3/27 (11.1%) | 3/27 (11.1%) | ||||
| Blood bilirubin increased | 0/10 (0%) | 0/11 (0%) | 2/27 (7.4%) | 2/27 (7.4%) | ||||
| Lipase increased | 0/10 (0%) | 0/11 (0%) | 2/27 (7.4%) | 2/27 (7.4%) | ||||
| Gamma-glutamyltransferase increased | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 2/27 (7.4%) | ||||
| Troponin T increased | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 3/27 (11.1%) | ||||
| Weight decreased | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 2/27 (7.4%) | ||||
| Platelet count decreased | 0/10 (0%) | 0/11 (0%) | 2/27 (7.4%) | 0/27 (0%) | ||||
| Troponin I increased | 1/10 (10%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Electrocardiogram abnormal | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Intraocular pressure increased | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Prothrombin time prolonged | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 2/10 (20%) | 3/11 (27.3%) | 13/27 (48.1%) | 6/27 (22.2%) | ||||
| Hypokalaemia | 2/10 (20%) | 1/11 (9.1%) | 3/27 (11.1%) | 2/27 (7.4%) | ||||
| Hypomagnesaemia | 1/10 (10%) | 0/11 (0%) | 1/27 (3.7%) | 2/27 (7.4%) | ||||
| Dehydration | 1/10 (10%) | 1/11 (9.1%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Hyperglycaemia | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 2/27 (7.4%) | ||||
| Hypoalbuminaemia | 0/10 (0%) | 0/11 (0%) | 2/27 (7.4%) | 1/27 (3.7%) | ||||
| Hyponatraemia | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 2/27 (7.4%) | ||||
| Hypophosphataemia | 0/10 (0%) | 0/11 (0%) | 2/27 (7.4%) | 1/27 (3.7%) | ||||
| Hypocalcaemia | 0/10 (0%) | 1/11 (9.1%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Hyperuricaemia | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 0/10 (0%) | 0/11 (0%) | 5/27 (18.5%) | 4/27 (14.8%) | ||||
| Myalgia | 0/10 (0%) | 2/11 (18.2%) | 3/27 (11.1%) | 1/27 (3.7%) | ||||
| Arthralgia | 1/10 (10%) | 0/11 (0%) | 1/27 (3.7%) | 2/27 (7.4%) | ||||
| Neck pain | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 2/27 (7.4%) | ||||
| Muscular weakness | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 1/27 (3.7%) | ||||
| Pain in extremity | 1/10 (10%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Musculoskeletal chest pain | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Tumour associated fever | 1/10 (10%) | 0/11 (0%) | 2/27 (7.4%) | 0/27 (0%) | ||||
| Basal cell carcinoma | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Cancer pain | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Nervous system disorders | ||||||||
| Dysgeusia | 1/10 (10%) | 2/11 (18.2%) | 1/27 (3.7%) | 2/27 (7.4%) | ||||
| Dizziness | 0/10 (0%) | 2/11 (18.2%) | 2/27 (7.4%) | 0/27 (0%) | ||||
| Neuropathy peripheral | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 2/27 (7.4%) | ||||
| Headache | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 2/27 (7.4%) | ||||
| Syncope | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Psychiatric disorders | ||||||||
| Depression | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 2/27 (7.4%) | ||||
| Confusional state | 0/10 (0%) | 2/11 (18.2%) | 0/27 (0%) | 0/27 (0%) | ||||
| Insomnia | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Haematuria | 1/10 (10%) | 0/11 (0%) | 2/27 (7.4%) | 0/27 (0%) | ||||
| Proteinuria | 0/10 (0%) | 0/11 (0%) | 1/27 (3.7%) | 2/27 (7.4%) | ||||
| Chromaturia | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 2/27 (7.4%) | ||||
| Renal colic | 0/10 (0%) | 1/11 (9.1%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Benign prostatic hyperplasia | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Pruritus genital | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Scrotal oedema | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 2/10 (20%) | 3/11 (27.3%) | 6/27 (22.2%) | 6/27 (22.2%) | ||||
| Dyspnoea | 0/10 (0%) | 4/11 (36.4%) | 4/27 (14.8%) | 4/27 (14.8%) | ||||
| Pneumonitis | 0/10 (0%) | 2/11 (18.2%) | 1/27 (3.7%) | 1/27 (3.7%) | ||||
| Dysphonia | 0/10 (0%) | 0/11 (0%) | 3/27 (11.1%) | 0/27 (0%) | ||||
| Epistaxis | 1/10 (10%) | 0/11 (0%) | 1/27 (3.7%) | 1/27 (3.7%) | ||||
| Productive cough | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 2/27 (7.4%) | ||||
| Rales | 0/10 (0%) | 2/11 (18.2%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Wheezing | 0/10 (0%) | 0/11 (0%) | 2/27 (7.4%) | 0/27 (0%) | ||||
| Dyspnoea exertional | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Nasal congestion | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Dermatitis acneiform | 7/10 (70%) | 6/11 (54.5%) | 13/27 (48.1%) | 12/27 (44.4%) | ||||
| Rash | 3/10 (30%) | 1/11 (9.1%) | 8/27 (29.6%) | 14/27 (51.9%) | ||||
| Pruritus | 0/10 (0%) | 3/11 (27.3%) | 5/27 (18.5%) | 7/27 (25.9%) | ||||
| Dry skin | 1/10 (10%) | 2/11 (18.2%) | 2/27 (7.4%) | 5/27 (18.5%) | ||||
| Rash maculo-papular | 1/10 (10%) | 1/11 (9.1%) | 3/27 (11.1%) | 0/27 (0%) | ||||
| Alopecia | 0/10 (0%) | 0/11 (0%) | 2/27 (7.4%) | 2/27 (7.4%) | ||||
| Erythema | 1/10 (10%) | 1/11 (9.1%) | 0/27 (0%) | 2/27 (7.4%) | ||||
| Pruritus generalised | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 2/27 (7.4%) | ||||
| Rash macular | 0/10 (0%) | 0/11 (0%) | 2/27 (7.4%) | 1/27 (3.7%) | ||||
| Rash papular | 0/10 (0%) | 1/11 (9.1%) | 1/27 (3.7%) | 1/27 (3.7%) | ||||
| Rash pruritic | 2/10 (20%) | 0/11 (0%) | 1/27 (3.7%) | 0/27 (0%) | ||||
| Acne | 0/10 (0%) | 0/11 (0%) | 0/27 (0%) | 2/27 (7.4%) | ||||
| Dermatitis | 1/10 (10%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Hyperhidrosis | 0/10 (0%) | 0/11 (0%) | 2/27 (7.4%) | 0/27 (0%) | ||||
| Dermatitis exfoliative generalised | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Ecchymosis | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Exfoliative rash | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Petechiae | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Rash erythematous | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Skin fissures | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Skin hyperpigmentation | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Skin lesion | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Skin reaction | 0/10 (0%) | 1/11 (9.1%) | 0/27 (0%) | 0/27 (0%) | ||||
| Urticaria | 1/10 (10%) | 0/11 (0%) | 0/27 (0%) | 0/27 (0%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 0/10 (0%) | 1/11 (9.1%) | 3/27 (11.1%) | 4/27 (14.8%) | ||||
| Hypotension | 1/10 (10%) | 0/11 (0%) | 1/27 (3.7%) | 1/27 (3.7%) | ||||
Limitations/Caveats
[Not Specified]
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:
NCT03271047
Other Study ID Numbers:
- ARRAY-162-202
- C4211004
- 2017-003464-12
First Posted:
Sep 1, 2017
Last Update Posted:
Jan 4, 2022
Last Verified:
Dec 1, 2021