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

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ClinicalTrials.gov Identifier: NCT04570839
Recruitment Status : Recruiting
First Posted : September 30, 2020
Last Update Posted : May 14, 2021
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Compugen Ltd

Tracking Information
First Submitted Date  ICMJE September 18, 2020
First Posted Date  ICMJE September 30, 2020
Last Update Posted Date May 14, 2021
Actual Study Start Date  ICMJE August 31, 2020
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 29, 2020)
  • The proportion of subjects with adverse events on the study. [ Time Frame: 2 years. ]
    The proportion of subjects with any adverse event (AE) per CTCAE v5.0.
  • The proportion of subjects with adverse events in the 1st cycle during dose escalation within the DLT window (28 days). [ Time Frame: Within the DLT window (1st 28 days) of the 1st cycle during dose escalation. ]
    The proportion of subjects with adverse events meeting the criteria of dose-limiting toxicities (DLTs) in the 1st 28 days of the 1st cycle of study treatment during dose escalation.
  • The recommended dose for expansion (RDFE) of the combination. [ Time Frame: 2 years. ]
    The dose of COM701 in combination with BMS-986207 and nivolumab for the expansion cohort.
  • The Area under the curve of COM701 in subjects receiving the 3-drug combination. [ Time Frame: 2 years. ]
    The PK profile of COM701 in combination with BMS-986207 and nivolumab.
Original Primary Outcome Measures  ICMJE
 (submitted: September 25, 2020)
  • The proportion of subjects with adverse events on the study. [ Time Frame: 2 years. ]
    Incidence of subjects with Adverse Events (AEs) per CTCAE v5.0.
  • The proportion of subjects with adverse events in the 1st cycle during dose escalation within the DLT window (28 days). [ Time Frame: DLT evaluation window in the 1st cycle of study treatment during dose escalation (DLT evaluation window in the 1st cycle (28 Days). ]
    Incidence of subjects with Dose Limiting Toxicities (DLTs).
  • The recommended dose for expansion (RDFE) of the combination. [ Time Frame: 2 years. ]
    The dose of COM701 in combination with BMS-986207 and nivolumab for the expansion cohort.
  • The Area under the curve of COM701 in subjects receiving the 3-drug combination. [ Time Frame: 2 years. ]
    The PK profile of COM701 in combination with BMS-986207 and nivolumab.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 25, 2020)
The objective response rate of subjects enrolled in cohorts 1-3. [ Time Frame: 3 years. ]
Objective response rate per RECIST v1.1.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE COM701 in Combination With BMS-986207 and Nivolumab in Subjects With Advanced Solid Tumors.
Official Title  ICMJE 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.
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:
Sequential dose escalation, followed by an expansion cohort upon determination of the recommended dose for expansion (RDFE) of COM701 in combination with BMS-986207 and nivolumab.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Endometrial Neoplasms
  • Ovarian Cancer
  • Solid Tumor
Intervention  ICMJE
  • Drug: COM701 in combination with BMS-986207 and nivolumab.
    Study treatment with COM701 in combination with BMS-986207 and nivolumab.
  • Drug: Nivolumab monotherapy.
    Study treatment with nivolumab monotherapy.
Study Arms  ICMJE
  • Experimental: Dose Escalation Cohorts.
    Up 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.
    Intervention: Drug: COM701 in combination with BMS-986207 and nivolumab.
  • Experimental: Cohort 1 Expansion Cohort A (ovarian cancer)
    Subjects 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.
    Intervention: Drug: COM701 in combination with BMS-986207 and nivolumab.
  • Active Comparator: Cohort 1 Expansion Cohort A (ovarian cancer).
    Subjects 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.
    Intervention: Drug: Nivolumab monotherapy.
  • Experimental: Cohort 2 Expansion Cohort (endometrial cancer).
    Single 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.
    Intervention: Drug: COM701 in combination with BMS-986207 and nivolumab.
  • Experimental: Cohort 3 Expansion Cohort (basket cohort - high PVRL2 tumors).
    Single 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.
    Intervention: Drug: COM701 in combination with BMS-986207 and nivolumab.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 25, 2020)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lead COM701 ClinInfo. 415-770-0922 COM701-03-101@cgen.com
Contact: Backup COM701 ClinInfo 415-770-0922 COM701-03-101@cgen.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04570839
Other Study ID Numbers  ICMJE CPG-03-101.
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Compugen Ltd
Study Sponsor  ICMJE Compugen Ltd
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Study Director: Lead COM701 ClinInfo Compugen Ltd
PRS Account Compugen Ltd
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP