NCT03271047|CompletedPhase 2ResultsFDA Drug

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

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

Pfizer ClinicalTrials.gov

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3 other identifiers

ARRAY-162-202C42110042017-003464-12

Study Type

interventional

Target

Locations

5 countries

Sites

Timeline

RegisteredSep 2017

StartedOct 2017

CompletionFeb 2021

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P50-P75 for phase_2

Timeline

Completed

Started Oct 2017

Typical duration for phase_2

Geographic Reach

5 countries

50 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

3.4 years study duration

First Submitted

Initial submission to the registry

August 31, 2017

Completed

1 day until next milestone

First Posted

Study publicly available on registry

September 1, 2017

Completed

2 months until next milestone

Study Start

First participant enrolled

October 18, 2017

Completed

3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 13, 2020

Completed

5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 25, 2021

Completed

8 months until next milestone

Results Posted

Study results publicly available

November 2, 2021

Completed

Last Updated

January 4, 2022

Status Verified

December 1, 2021

Enrollment Period

3 years

First QC Date

August 31, 2017

Results QC Date

October 4, 2021

Last Update Submit

December 8, 2021

Conditions

MSS RAS-mutant Colorectal Cancer

Keywords

cancer

Outcome Measures

Primary Outcomes (2)

Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLT)
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.
Cycle 1: Day 1 up to Day 28
Phase 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
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.
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)

Secondary Outcomes (10)

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)
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)
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)
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)
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)
+5 more secondary outcomes

Study Arms (4)

Phase 1b / Arm 1A

EXPERIMENTAL

binimetinib + nivolumab

Drug: binimetinibDrug: nivolumab

Phase 1b / Arm 1B

EXPERIMENTAL

binimetinib + nivolumab + ipilimumab

Drug: binimetinibDrug: nivolumabDrug: ipilimumab

Phase 2 / Arm 2A

EXPERIMENTAL

binimetinib + nivolumab

Drug: binimetinibDrug: nivolumab

Phase 2 / Arm 2B

EXPERIMENTAL

binimetinib + nivolumab + ipilimumab

Drug: binimetinibDrug: nivolumabDrug: ipilimumab

Interventions

binimetinibDRUG

Orally, twice daily.

Phase 1b / Arm 1APhase 1b / Arm 1BPhase 2 / Arm 2APhase 2 / Arm 2B

nivolumabDRUG

Intravenously (IV) every 4 weeks (Q4W)

Phase 1b / Arm 1APhase 1b / Arm 1BPhase 2 / Arm 2APhase 2 / Arm 2B

ipilimumabDRUG

intravenously (IV) every 8 weeks (Q8W)

Phase 1b / Arm 1BPhase 2 / Arm 2B

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Pfizerlead
Bristol-Myers Squibbcollaborator

Study Sites (50)

UCLA Hematology/Oncology

Los Angeles, California, 90095, United States

Location

UCLA Hematology/Oncology - Santa Monica

Santa Monica, California, 90404, United States

Location

Christiana Care Health Services, Helen F. Graham Cancer Center Pharmacy, Suite 3200

Newark, Delaware, 19713, United States

Location

Christiana Care Health Services, Helen F. Graham Cancer Center

Newark, Delaware, 19713, United States

Location

Christiana Care Oncology Hematology, Helen F Graham Cancer Center, Suite 2400

Newark, Delaware, 19713, United States

Location

Medical Oncology Hematology Consultants, PA, Helen F. Graham Cancer Center

Newark, Delaware, 19713, United States

Location

Christiana Care Health Services, Christiana Hospital

Newark, Delaware, 19718, United States

Location

Georgetown University Medical Center Department of Pharmacy, Research

Washington D.C., District of Columbia, 20007, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Hematology Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida, 34952, United States

Location

Indiana CTSI Clinical Research Center (ICRC)