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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 : August 3, 2021
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Compugen Ltd

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.

Condition or disease Intervention/treatment Phase
Endometrial Neoplasms Ovarian Cancer Solid Tumor Head and Neck Cancer Drug: COM701 in combination with BMS-986207 and nivolumab. Phase 1 Phase 2

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 the 3-drug combination.

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, 2 and 4 will not be enrolled into this cohort.

Cohort 4: subjects with HNSCC. This cohort will enroll subjects who have received treatment with an immune checkpoint inhibitor or subjects who have received treatment with chemotherapy but not an immune checkpoint inhibitor. All subjects enrolled in this cohort will receive study treatment with the 3-drug combination.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
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
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.
Actual Study Start Date : August 31, 2020
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
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.
Drug: COM701 in combination with BMS-986207 and nivolumab.
Study treatment with the 3 drug combination (COM701 in combination with BMS-986207 and nivolumab).

Experimental: Cohort 1 Expansion Cohort A (ovarian cancer)
Single arm: 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.
Drug: COM701 in combination with BMS-986207 and nivolumab.
Study treatment with the 3 drug combination (COM701 in combination with BMS-986207 and nivolumab).

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.
Drug: COM701 in combination with BMS-986207 and nivolumab.
Study treatment with the 3 drug combination (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.
Drug: COM701 in combination with BMS-986207 and nivolumab.
Study treatment with the 3 drug combination (COM701 in combination with BMS-986207 and nivolumab).

Experimental: Cohort 4 Expansion Cohort (Head and Neck cancer).

Two arms: subjects with head and neck cancer. Equal number of subjects in each of the 2 arms. One arm will enroll subjects who have not previously received treatment with an immune checkpoint inhibitor, the other arm will enroll subjects who have received prior treatment with an immune checkpoint inhibitor.

All subjects will receive study treatment with COM701 in combination with BMS-986207 and nivolumab. All study drugs will be administered IV every 4 weeks.

Drug: COM701 in combination with BMS-986207 and nivolumab.
Study treatment with the 3 drug combination (COM701 in combination with BMS-986207 and nivolumab).




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.


Secondary Outcome Measures :
  1. The objective response rate of subjects enrolled in cohorts 1-3. [ Time Frame: 3 years. ]
    Objective response rate per RECIST v1.1.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).
  • Cohort 4 (Head and Neck cancer)
  • Histologically confirmed recurrent or metastatic HNSCC (oral cavity, oropharynx, larynx, hypopharynx, nasopharynx, paranasal sinus, nasopharyngeal)
  • Cohort 4a - IO naïve. Eligible subjects can be systemic therapy naïve (frontline) or platinum failure.
  • Cohort 4b - IO failure. No limitations on the number of prior lines of systemic therapy.

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.
  • Cohort 4: Subjects who have received prior therapy with COM701 (or any inhibitor of PVRIG), anti-TIGIT antibody, anti-CTLA-4 antibody, anti-OX-40 antibody, anti-CD137 antibody. Subjects in cohort 4a must be IO-naïve.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04570839


Contacts
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Contact: Lead COM701 ClinInfo. 415-770-0922 COM701-03-101@cgen.com
Contact: Backup COM701 ClinInfo 415-770-0922 COM701-03-101@cgen.com

Locations
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United States, Illinois
University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
Contact: COM701 Study Director    415-770-0922    COM701-03-101@cgen.com   
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: COM701 Study Director    415-770-0922    COM701-03-101@cgen.com   
United States, Michigan
START Midwest. Recruiting
Grand Rapids, Michigan, United States, 49503
Contact: COM701 Study Director.    415-770-0922    COM701-03-101@cgen.com   
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Contact: COM701 Study Director    415-770-0922    COM701-03-101@cgen.com   
United States, Tennessee
The University of Tennessee WEST Cancer Center. Recruiting
Memphis, Tennessee, United States, 38138
Contact: COM701 Study Director    415-770-0922    COM701-03-101@cgen.com   
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: COM701 Study Director    415-770-0922    COM701-03-101@cgen.com   
The START Center for Cancer Care. Recruiting
San Antonio, Texas, United States, 78229
Contact: COM701 Study Director    415-770-0922    COM701-03-101@cgen.com   
Sponsors and Collaborators
Compugen Ltd
Bristol-Myers Squibb
Investigators
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Study Director: Lead COM701 ClinInfo Compugen Ltd
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Responsible Party: Compugen Ltd
ClinicalTrials.gov Identifier: NCT04570839    
Other Study ID Numbers: CPG-03-101.
First Posted: September 30, 2020    Key Record Dates
Last Update Posted: August 3, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Compugen Ltd:
TIGIT
PVRIG
checkpoint inhibitor
Immune checkpoint
Immuno-oncology
CD226
CD112
CD155
Solid tumor
Ovarian cancer
Endometrial cancer
PVRL2
Basket study
Opdivo
DNAM
Additional relevant MeSH terms:
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Ovarian Neoplasms
Endometrial Neoplasms
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Uterine Neoplasms
Uterine Diseases
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action