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Study of Binimetinib + Nivolu...

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

Last Updated: 2022-01-04

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

75 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-10-18

Study Completion Date

2021-02-25

Brief Summary

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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.

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Detailed Description

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Conditions

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MSS RAS-mutant Colorectal Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

In phase 1 it is sequential and then in phase 2 it is parallel.

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase 1b / Arm 1A

binimetinib + nivolumab

Group Type EXPERIMENTAL

binimetinib

Intervention Type DRUG

Orally, twice daily.

nivolumab

Intervention Type DRUG

Intravenously (IV) every 4 weeks (Q4W)

Phase 1b / Arm 1B

binimetinib + nivolumab + ipilimumab

Group Type EXPERIMENTAL

binimetinib

Intervention Type DRUG

Orally, twice daily.

nivolumab

Intervention Type DRUG

Intravenously (IV) every 4 weeks (Q4W)

ipilimumab

Intervention Type DRUG

intravenously (IV) every 8 weeks (Q8W)

Phase 2 / Arm 2A

binimetinib + nivolumab

Group Type EXPERIMENTAL

binimetinib

Intervention Type DRUG

Orally, twice daily.

nivolumab

Intervention Type DRUG

Intravenously (IV) every 4 weeks (Q4W)

Phase 2 / Arm 2B

binimetinib + nivolumab + ipilimumab

Group Type EXPERIMENTAL

binimetinib

Intervention Type DRUG

Orally, twice daily.

nivolumab

Intervention Type DRUG

Intravenously (IV) every 4 weeks (Q4W)

ipilimumab

Intervention Type DRUG

intravenously (IV) every 8 weeks (Q8W)

Interventions

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binimetinib

Orally, twice daily.

Intervention Type DRUG

nivolumab

Intravenously (IV) every 4 weeks (Q4W)

Intervention Type DRUG

ipilimumab

intravenously (IV) every 8 weeks (Q8W)

Intervention Type DRUG

Eligibility Criteria

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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

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.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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UCLA Hematology/Oncology

Los Angeles, California, United States

Site Status

UCLA Hematology/Oncology - Santa Monica

Santa Monica, California, United States

Site Status

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

Newark, Delaware, United States

Site Status

Christiana Care Health Services, Helen F. Graham Cancer Center

Newark, Delaware, United States

Site Status

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

Newark, Delaware, United States

Site Status

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

Newark, Delaware, United States

Site Status

Christiana Care Health Services, Christiana Hospital

Newark, Delaware, United States

Site Status

Georgetown University Medical Center Department of Pharmacy, Research

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

Site Status

Georgetown University Medical Center

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

Site Status