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.
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
Drug | Synonyms | Arms |
---|
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
Name | Type | Description | Interventions |
---|
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. | - COM701 in combination with BMS-986207 and nivolumab.
|
Cohort 1 Expansion Cohort A (ovarian cancer) | Experimental | 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. | - COM701 in combination with BMS-986207 and nivolumab.
|
Cohort 1 Expansion Cohort A (ovarian cancer). | Active Comparator | 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. | |
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. | - 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. | - 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