COM701 (an Inhibitor of PVRIG) in Subjects With Advanced Solid Tumors.
- Interventional
- Recruiting
- NCT03667716
Contact Information
A Phase 1a/1b Study of COM701 as Monotherapy and In Combination With an Anti-PD-1 Antibody in Subjects With Advanced Solid Tumors.
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.
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.
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers?
No
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.
- 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.