Clinical Trials /

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

NCT03271047

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: ARRAY-162-202
  • NCT ID: NCT03271047

Conditions

  • MSS
  • RAS-mutant Colorectal Cancer

Interventions

DrugSynonymsArms
binimetinibPhase 1b / Arm 1A
nivolumabPhase 1b / Arm 1A
ipilimumabPhase 1b / Arm 1B

Purpose

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 Arms

NameTypeDescriptionInterventions
Phase 1b / Arm 1AExperimentalbinimetinib + nivolumab
  • binimetinib
  • nivolumab
Phase 1b / Arm 1BExperimentalbinimetinib + nivolumab + ipilimumab
  • binimetinib
  • nivolumab
  • ipilimumab
Phase 2 / Arm 2AExperimentalbinimetinib + nivolumab
  • binimetinib
  • nivolumab
Phase 2 / Arm 2BExperimentalbinimetinib + nivolumab + ipilimumab
  • binimetinib
  • nivolumab
  • ipilimumab

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:(Phase 1b) Incidence of dose-limiting toxicities (DLTs) resulting from binimetinib in combination with nivolumab
Time Frame:Duration of each treatment cycle, 28 days
Safety Issue:
Description:

Secondary Outcome Measures

Measure:(Phase 1b) Objective Response Rate (ORR)
Time Frame:Duration of each treatment cycle, 28 days
Safety Issue:
Description:
Measure:(Phase 1b and Phase 2) Duration of Response (DOR)
Time Frame:Duration of each treatment cycle, 28 days
Safety Issue:
Description:
Measure:(Phase 1b and Phase 2) Rate of complete response (CR)
Time Frame:Duration of each treatment cycle, 28 days
Safety Issue:
Description:
Measure:(Phase 1b and Phase 2) Incidence and severity of adverse events (AEs)
Time Frame:Duration of each treatment cycle, 28 days
Safety Issue:
Description:
Measure:(Phase 1b and Phase 2) Sparse plasma concentrations for binimetinib
Time Frame:Duration of each treatment cycle, 28 days
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Array BioPharma

Trial Keywords

  • cancer

Last Updated