COM701 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 a programmed cell death protein 1 (PD-1) inhibitor.
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 a PD-1 inhibitor in subjects with
advanced solid tumors. Cohort expansion will be explored evaluating COM701 monotherapy and in
combination with a PD-1 inhibitor 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 a PD-1 inhibitor):
- 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.
- Endometrial cancer: Subjects with locally advanced or metastatic endometrial cancer, Disease recurrence or progression during or after prior therapy that included platinum-based chemotherapy.
- 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).
- 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).
- CRC (microsatellite stable, KRAS mutation)
- 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 a PD-1 inhibitor):
- 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.
- Endometrial cancer: Subjects with locally advanced or metastatic endometrial cancer, Disease recurrence or progression during or after prior therapy that included platinum-based chemotherapy.
- 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).
- 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).
- CRC (microsatellite stable, KRAS mutation)
- 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.