COM701 (an Inhibitor of PVRIG) in Subjects With Advanced Solid Tumors.

Breast Cancer Clinical Trial

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03667716
• Other study ID #: CPG-01-001
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 6, 2018
• Est. completion date: May 31, 2024

Study information

• Verified date: February 2024
• Source: Compugen Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 140
• Est. completion date: May 31, 2024
• Est. primary completion date: February 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Cancer
• Breast Cancer
• Breast Neoplasms
• Colo-rectal Cancer
• Endometrial Cancer
• Endometrial Neoplasms
• Lung Cancer
• Lung Neoplasm
• Lung Neoplasms
• Neoplasm Malignant
• Neoplasms
• Ovarian Cancer
• Ovarian Neoplasm
• Ovarian Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• COM701
COM701 monotherapy.
• COM701 with Opdivo (Nivolumab).
COM701 in combination with Opdivo (Nivolumab).

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Cleveland Clinic.	Cleveland	Ohio
United States	START Midwest.	Grand Rapids	Michigan
United States	M D Anderson Cancer Center.	Houston	Texas
United States	University of California Los Angeles (UCLA).	Los Angeles	California
United States	The University of Tennessee WEST Cancer Center.	Memphis	Tennessee
United States	Sarah Cannon Research Institute.	Nashville	Tennessee
United States	Columbia University	New York	New York
United States	The START Center for Cancer Care.	San Antonio	Texas
United States	Florida Cancer Specialists	Sarasota	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Compugen Ltd	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of subjects with Adverse Events (AEs) as per CTCAE v4.03 and Dose-Limiting Toxicities (DLTs).	To evaluate the safety profile of COM701 monotherapy and in combination with nivolumab.	DLT evaluation window in the 1st cycle (21 or 28 days).
Primary	Determine the maximum tolerated dose (MTD) and/or the recommended dose for expansion (RDFE) (COM701 monotherapy and in combination with nivolumab).		Approximately 2 year.
Secondary	Incidence of subjects with Anti-COM701 antibody.	Immunogenicity of COM701 monotherapy and in combination with nivolumab.	Approximately 2 years.
Secondary	Overall Response Rate as per RECIST v1.1	Preliminary antitumor activity of COM701 in combination with nivolumab.	Approximately 2 years.