Clinical Trials /

COM701 in Combination With BMS-986207 and Nivolumab in Subjects With Advanced Solid Tumors.

NCT04570839

Description:

This is a phase 1/2 open label sequential dose escalation and cohort expansion study evaluating the safety, tolerability and preliminary antitumor activity of COM701 in combination with BMS-986207 and nivolumab in patients with advanced solid tumors.

Related Conditions:
  • Endometrial Carcinoma
  • Fallopian Tube Carcinoma
  • Malignant Ovarian Epithelial Tumor
  • Malignant Solid Tumor
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: COM701 in Combination With BMS-986207 and Nivolumab in Subjects With Advanced Solid Tumors.
  • Official Title: A Phase 1/2 Study Evaluating the Safety, Tolerability and Preliminary Antitumor Activity of COM701 in Combination With BMS-986207 (Anti-TIGIT Antibody) and Nivolumab in Subjects With Advanced Solid Tumors.

Clinical Trial IDs

  • ORG STUDY ID: CPG-03-101.
  • NCT ID: NCT04570839

Conditions

  • Endometrial Neoplasms
  • Ovarian Cancer
  • Solid Tumor

Interventions

DrugSynonymsArms
COM701 in combination with BMS-986207 and nivolumab.Cohort 1 Expansion Cohort A (ovarian cancer)
Nivolumab monotherapy.Cohort 1 Expansion Cohort A (ovarian cancer).

Purpose

This is a phase 1/2 open label sequential dose escalation and cohort expansion study evaluating the safety, tolerability and preliminary antitumor activity of COM701 in combination with BMS-986207 and nivolumab in patients with advanced solid tumors.

Detailed Description

      This phase 1/2 study evaluates the safety/tolerability, pharmacokinetics and preliminary
      antitumor activity of COM701 an inhibitor of poliovirus receptor related immunoglobulin
      domain containing (PVRIG) in combination with BMS-986207 (an inhibitor of TIGIT) and
      nivolumab in subjects with advanced solid tumors. The study will consist of 2 parts (part 1 -
      dose escalation and part 2 - dose expansion).

      Part 1: escalating doses of COM701 will be combined with fixed doses of BMS-986207 and
      nivolumab. Upon completion of dose escalation a recommended dose of COM701 in combination
      with BMS-986207 and nivolumab (3-drug combination) will be determined.

      Part 2: subjects will be administered the recommended dose of COM701 in combination with
      BMS-986207 and nivolumab. Subjects will be enrolled into one of three cohorts based on their
      cancer type.

      Cohort 1: subjects with platinum resistant/refractory ovarian cancer, primary peritoneal or
      fallopian tube cancer will receive study treatment with either the 3-drug combination or
      nivolumab monotherapy.

      Cohort 2: subjects with MSS- endometrial cancer will receive study treatment with the 3-drug
      combination.

      Cohort 3 (Basket cohort): subjects with tumors that have high expression of a biomarker
      (PVRL2) will receive study treatment with the 3-drug combination. Subjects with tumor types
      in cohorts 1 and 2 will not be enrolled into this cohort.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation Cohorts.ExperimentalUp to 5 sequential dose escalation cohorts of COM701 in combination with fixed doses of BMS-986207 and nivolumab. All study drugs will be administered IV every 4 weeks until a maximum tolerated dose or recommended dose for expansion is identified.
  • COM701 in combination with BMS-986207 and nivolumab.
Cohort 1 Expansion Cohort A (ovarian cancer)ExperimentalSubjects with platinum resistant/refractory epithelial ovarian cancer, primary peritoneal or fallopian tube cancer will be randomized to receive study treatment with COM701 in combination with BMS-986207 and nivolumab. The study drugs will be administered IV every 4 weeks.
  • COM701 in combination with BMS-986207 and nivolumab.
Cohort 1 Expansion Cohort A (ovarian cancer).Active ComparatorSubjects with platinum resistant/refractory epithelial ovarian cancer, primary peritoneal or fallopian tube cancer will be randomized to receive study treatment with nivolumab monotherapy. The study drug will be administered IV every 4 weeks.
  • Nivolumab monotherapy.
Cohort 2 Expansion Cohort (endometrial cancer).ExperimentalSingle arm: subjects with MSS-endometrial cancer will receive study treatment with COM701 in combination with BMS-986207 and nivolumab. All study drugs will be administered IV every 4 weeks.
  • COM701 in combination with BMS-986207 and nivolumab.
Cohort 3 Expansion Cohort (basket cohort - high PVRL2 tumors).ExperimentalSingle arm: subjects with tumor types with high expression of PVRL2 will receive study treatment with COM701 in combination with BMS-986207 and nivolumab. All study drugs will be administered IV every 4 weeks.
  • COM701 in combination with BMS-986207 and nivolumab.

Eligibility Criteria

        Key Inclusion Criteria:

          -  Histologically or cytologically confirmed, locally advanced or metastatic solid
             malignancy and has exhausted all available standard therapy or is not a candidate for
             the available standard therapy.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

          -  During dose escalation - Subjects who received prior therapy with anti-PD-1,
             anti-PD-L1, anti- CTLA-4, OX-40, CD137, etc., are eligible.

        During cohort expansion: All subjects must have measurable disease as defined by RECIST
        v1.1.

        Expansion Cohorts:

          -  Cohort 1 (subjects with advanced epithelial ovarian, fallopian tube, or primary
             peritoneal carcinoma)

          -  Subject must have platinum refractory/resistant ovarian cancer defined as
             refractoriness to platinum-containing regimen or disease recurrence < 6 months after
             completion of a platinum-containing regimen

          -  Cohort 2 (endometrial cancer cohort)

          -  Subjects with locally advanced or metastatic microsatellite stable endometrial cancer
             with disease recurrence or progression during or after prior therapy that included
             platinum-based chemotherapy.

          -  Subjects must have documented MSS status by an approved test e.g. genomic testing, IHC
             for mismatch repair proficient.

          -  Subjects must have received no more than 2 prior systemic cytotoxic therapies; there
             are no limits to the number of prior endocrine or antiangiogenic regimens

          -  Cohort 3 (basket cohort, excludes tumor types in cohorts 1 and 2)

          -  Tumor types with high expression of PVRL2 (determined by central testing).

        Key Exclusion Criteria:

          -  Active autoimmune disease requiring systemic therapy in the last 2 years prior to the
             first dose of COM701.

          -  Symptomatic interstitial lung disease or inflammatory pneumonitis.

          -  History of immune-related events that lead to immunotherapy treatment discontinuation.

          -  Untreated or symptomatic central nervous system (CNS) metastases.

        Key Exclusion Criteria For Dose Expansion Cohorts:

          -  Cohort 1: Prior therapy with an anti-PD-1/PD-L1/2, COM701 (or any inhibitor of PVRIG),
             anti-TIGIT antibody, anti-CTLA-4 antibody, anti-OX-40 antibody, anti-CD137 antibody.

          -  Cohort 2: Prior therapy with COM701 (or any inhibitor of PVRIG) or anti-TIGIT
             antibody. Subjects with MSI-H endometrial cancer are ineligible.

          -  Cohort 3: Prior therapy with COM701 (or any inhibitor of PVRIG) or anti-TIGIT antibody
             are ineligible.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The proportion of subjects with adverse events on the study.
Time Frame:2 years.
Safety Issue:
Description:The proportion of subjects with any adverse event (AE) per CTCAE v5.0.

Secondary Outcome Measures

Measure:The objective response rate of subjects enrolled in cohorts 1-3.
Time Frame:3 years.
Safety Issue:
Description:Objective response rate per RECIST v1.1.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Compugen Ltd

Trial Keywords

  • TIGIT
  • PVRIG
  • checkpoint inhibitor
  • Immune checkpoint
  • Immuno-oncology
  • CD226
  • CD112
  • CD155
  • Solid tumor
  • Ovarian cancer
  • Endometrial cancer
  • PVRL2
  • Basket study
  • Opdivo
  • DNAM

Last Updated

October 1, 2020