Clinical trial NCT04570839: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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
Lead sponsor: Compugen Ltd
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2020-09-30
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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 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.

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).
* 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.

Primary outcomes:
measure: The proportion of subjects with adverse events on the study.
timeFrame: 2 years.
measure: The proportion of subjects with adverse events in the 1st cycle during dose escalation within the DLT window (28 days).
timeFrame: Within the DLT window (1st 28 days) of the 1st cycle during dose escalation.
measure: The recommended dose for expansion (RDFE) of the combination.
timeFrame: 2 years.
measure: The Area under the curve of COM701 in subjects receiving the 3-drug combination.
timeFrame: 2 years.
Secondary outcomes:
measure: The objective response rate of subjects enrolled in cohorts 1-4.
timeFrame: 3 years.
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University Oncology Center.
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Grand Rapids
country: United States
facility: START Midwest.
state: Michigan
city: New York
country: United States
facility: Columbia University
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Center.
state: Pennsylvania
city: Memphis
country: United States
facility: The University of Tennessee WEST Cancer Center.
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: The START Center for Cancer Care.
state: Texas
Study officials:
affiliation: Compugen Ltd
name: Lead COM701 ClinInfo
role: STUDY_DIRECTOR
References: