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

NCT04570839 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CPG-03-101.
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 9

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.

Conditions

Endometrial Neoplasms; Ovarian Cancer; Solid Tumor; Head and Neck Cancer

Keywords

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

Outcome Measures

Primary Outcomes (4)

• The proportion of subjects with adverse events on the study.

  The proportion of subjects with any adverse event (AE) per CTCAE v5.0.

  2 years.

• The proportion of subjects with adverse events in the 1st cycle during dose escalation within the DLT window (28 days).

  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.

  Within the DLT window (1st 28 days) of the 1st cycle during dose escalation.

• The recommended dose for expansion (RDFE) of the combination.

  The dose of COM701 in combination with BMS-986207 and nivolumab for the expansion cohort.

  2 years.

• The Area under the curve of COM701 in subjects receiving the 3-drug combination.

  The PK profile of COM701 in combination with BMS-986207 and nivolumab.

  2 years.

Secondary Outcomes (1)

• The objective response rate of subjects enrolled in cohorts 1-4.

  3 years.

Study Arms (5)

Dose Escalation Cohorts.

EXPERIMENTAL

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.

Cohort 1 Expansion Cohort A (ovarian cancer)

EXPERIMENTAL

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.

Cohort 2 Expansion Cohort (endometrial cancer).

EXPERIMENTAL

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.

Cohort 3 Expansion Cohort (basket cohort - high PVRL2 tumors).

EXPERIMENTAL

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.

Cohort 4 Expansion Cohort (Head and Neck cancer).

EXPERIMENTAL

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.

Interventions

COM701 in combination with BMS-986207 and nivolumab. DRUG

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

Cohort 1 Expansion Cohort A (ovarian cancer); Cohort 2 Expansion Cohort (endometrial cancer).; Cohort 3 Expansion Cohort (basket cohort - high PVRL2 tumors).; Cohort 4 Expansion Cohort (Head and Neck cancer).; Dose Escalation Cohorts.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Compugen Ltd: lead
• Bristol-Myers Squibb: collaborator

Study Sites (9)

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Johns Hopkins University Oncology Center.

Baltimore, Maryland, 21231, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

START Midwest.

Grand Rapids, Michigan, 49503, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of Pittsburgh Cancer Center.

Pittsburgh, Pennsylvania, 15232, United States

Location

The University of Tennessee WEST Cancer Center.

Memphis, Tennessee, 38138, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

The START Center for Cancer Care.

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Endometrial Neoplasms; Ovarian Neoplasms; Head and Neck Neoplasms

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Lead COM701 ClinInfo

  Compugen Ltd

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 18, 2020
• First Posted: September 30, 2020
• Study Start: August 31, 2020
• Primary Completion: May 15, 2024
• Study Completion: May 15, 2024
• Last Updated: July 18, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)