Clinical trial NCT03667716: COM701 (an Inhibitor of PVRIG) in Subjects With Advanced Solid Tumors.
Official title: A Phase 1a/1b Study of COM701 as Monotherapy and In Combination With an Anti-PD-1 Antibody in Subjects With Advanced Solid Tumors.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Cancer
Ovarian Cancer
Breast Cancer
Lung Cancer
Endometrial Cancer
Ovarian Neoplasm
Triple Negative Breast Cancer
Lung Neoplasm
Neoplasm Malignant
Colo-rectal Cancer
Keywords: PVRIG
advanced cancer
checkpoint inhibitor
DNAM (DNAX Accessory molecule 1)
PD-1 inhibitor
CD112
CD 112R
Poliovirus receptor-related immunoglobulin
PVRL2
Nivolumab
opdivo
TIGIT antibody
COM902
Lead sponsor: Compugen Ltd
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2018-09-12
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1 open label sequential dose escalation and cohort expansion study evaluating the safety, tolerability and preliminary clinical activity of COM701 as monotherapy and in combination with nivolumab.

Detailed description: This Phase 1 study evaluates the safety, tolerability, Pharmacokinetics (PK) and preliminary clinical activity of COM701 an inhibitor of poliovirus receptor related immunoglobulin domain containing (PVRIG) as monotherapy and in combination with nivolumab in subjects with advanced solid tumors. Cohort expansion will be explored evaluating COM701 monotherapy and in combination with nivolumab in subjects with the following select tumor types (Non-Small cell lung cancer (NSCLC), Ovarian, Breast (including Triple negative breast cancer (TNBC) and endometrial cancer. Other tumor types such as CRC-MSS, CRC-KRAS mutant will be enrolled based on emerging clinical activity data.

Eligibility criteria: Key Inclusion Criteria:

* Subject has Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
* Subjects who received prior immune-stimulatory antitumor agents, such as anti-PD-1, anti-PD-L1, anti-CTLA-4, OX-40, CD137, etc. are eligible.
* Histologically or cytologically confirmed, locally advanced or metastatic solid malignancy and has exhausted all the available standard therapy or is not a candidate for the available standard therapy.

Select Tumor Types (COM701 monotherapy cohort expansion; COM701 in combination with nivolumab):

* Breast cancer (TNBC): Histologically confirmed incurable, advanced estrogen receptor-, progesterone receptor-, and human epidermal growth factor receptor 2 (HER2)-negative (triple-negative) adenocarcinoma of the breast, as defined by the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) guidelines. Disease recurrence or progression during or after at least one systemic treatment that included an anthracycline and/or a taxane in the neoadjuvant, adjuvant, or metastatic setting. Subjects must have progressed after a poly ADP-ribose polymerase (PARP) inhibitor for patients with deleterious or suspected deleterious germline breast cancer susceptibility gene (BRCA) mutated metastatic breast cancer. P1b COM701 + nivolumab expansion cohort, COM701 monotherapy expansion cohort.
* Endometrial cancer: Subjects with locally advanced or metastatic endometrial cancer, disease recurrence or progression during or after prior therapy that included platinum-based chemotherapy. P1b COM701 + nivolumab expansion cohort, COM701 monotherapy expansion cohort.
* Ovarian cancer: Disease recurrence or progression during or after prior therapy that included: surgical resection, platinum agent, PARP inhibitor (for subjects with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer or as a maintenance therapy for subjects who have had complete or partial response to platinum-based therapy). P1b COM701 + nivolumab expansion cohort, COM701 monotherapy expansion cohort.
* NSCLC: Documented stage IIIB or IV or recurrent NSCLC, Disease recurrence or progression during or after prior treatment that included: platinum agent, targeted therapy such as a TKI (if with biopsy-confirmed cytogenetic mutation eg EGFR, ROS, BRAF). COM701 monotherapy expansion cohort.
* CRC (microsatellite stable, KRAS mutation) - P1b COM701 + nivolumab expansion cohort, COM701 monotherapy expansion cohort.
* For Phase 1a monotherapy expansion and Phase 1b only: subject has at least one measurable lesion that could be followed during the study according to RECIST v1.1.

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.
* Impaired cardiac function or clinically significant cardiac disease, including any of the following: a) Unstable angina pectoris ≤ 6 months prior to first scheduled dose of COM701; b) Acute myocardial infarction ≤ 6 months prior to first scheduled dose of COM701.

Primary outcomes:
measure: Incidence of subjects with Adverse Events (AEs) as per CTCAE v4.03 and Dose-Limiting Toxicities (DLTs).
timeFrame: DLT evaluation window in the 1st cycle (21 or 28 days).
measure: Determine the maximum tolerated dose (MTD) and/or the recommended dose for expansion (RDFE) (COM701 monotherapy and in combination with nivolumab).
timeFrame: Approximately 2 year.
Secondary outcomes:
measure: Incidence of subjects with Anti-COM701 antibody.
timeFrame: Approximately 2 years.
measure: Overall Response Rate as per RECIST v1.1
timeFrame: Approximately 2 years.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles (UCLA).
state: California
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
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: Cleveland
country: United States
facility: Cleveland Clinic.
state: Ohio
city: Memphis
country: United States
facility: The University of Tennessee WEST Cancer Center.
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute.
state: Tennessee
city: Houston
country: United States
facility: M D Anderson Cancer Center.
state: Texas
city: San Antonio
country: United States
facility: The START Center for Cancer Care.
state: Texas
Study officials:
affiliation: Compugen USA, Inc.
name: COM701 Study Director
role: STUDY_DIRECTOR
References: