COM902 (A TIGIT Inhibitor) in Subjects With Advanced Malignancies

Phase 1 open label sequential dose escalation and cohort expansion study evaluating the safety, tolerability and preliminary antitumor activity of COM902 as monotherapy and in combination with COM701 in subjects with advanced malignancies.

Advanced Cancer, Ovarian Cancer, Lung Cancer, Colon Cancer, Plasma Cell Neoplasm, Multiple Myeloma, HNSCC, Microsatellite Stable Colorectal Carcinoma, MSS-CRC

Monotherapy dose escalation. COM902 monotherapy administered IV every 3 weeks in sequential dose escalation. Up to 7 dose escalation cohorts may be evaluated until a maximum tolerated dose or recommended dose for expansion (RDFE) is identified.

COM902 will be combined with COM701 for evaluation of safety and tolerability. All study drugs will be administered IV every 3 weeks.

COM902 monotherapy at the RDFE - in subjects with multiple myeloma. COM902 will be administered IV every 3 weeks.

COM902 + COM701 (both at the RDFE) evaluated in subjects with select tumor types who have exhausted standard of care treatment: HNSCC, CRC (MSS), NSCLC. All study drugs will be administered IV every 3 weeks.

Triplet combination of COM902 + COM701 + Pembrolizumab evaluated in subjects with MSS-CRC. All study drugs will be administered IV every 3 weeks.

Triplet combination of COM902 + COM701 + Pembrolizumab evaluated in subjects with PROC. All study drugs will be administered IV every 3 weeks.

COM902 monotherapy administered IV every 3 weeks in sequential dose escalation doses in cohorts of subjects.

Both study drugs will be evaluated at the RDFE for assessment of safety and tolerability. All study drugs will be administered IV every 3 weeks.

COM902 monotherapy (RDFE) in subjects with multiple myeloma. COM902 will be administered IV every 3 weeks.

COM902 in combination with COM701 (both at RDFE) in subjects with select tumor types who have exhausted standard treatment - HNSCC, CRC (MSS), NSCLC. All study drugs will be administered IV every 3 weeks.

Incidence of subjects with Adverse Events (AEs) as per CTCAE v5.0 and Dose-Limiting Toxicities (DLTs).

To identify the maximum tolerated dose (MTD) and/or recommended dose for expansion of COM902 monotherapy and in combination with COM701.

Evaluation of a dose of COM902 monotherapy and in combination with COM701 that is well tolerated by subjects.

To characterize the pharmacokinetic (PK) profile of COM902 as monotherapy and in combination with COM701.

Evaluation of parameters of COM902 monotherapy or in combination with COM701 exposure such as Maximum Plasma Concentration [Cmax]).

Incidence of subjects on the Triplet combination (COM902 + COM701 + Pembrolizumab) with Adverse Events (AEs) per CTCAE v5.0.

Evaluation of anti drug antibody to COM902 (monotherapy) or COM902, COM701 when administered in combination.

Evaluation of the preliminary antitumor activity of COM902 as monotherapy and in combination with COM701.

An assessment of preliminary antitumor activity eg ORR with COM902 monotherapy and COM902 in combination with COM701.

Key Inclusion Criteria: Subjects with histologically/cytologically confirmed advanced malignancy (solid tumor) who must have exhausted all available standard therapy, or not a candidate for standard therapy. Subject is able to provide written, informed consent before initiation of any study related procedures, and is able, in the opinion of the investigator, to comply with all the requirements of the study. Subject has Eastern Cooperative Oncology Group (ECOG) performance status 0-1. For Triplet combination MSS-CRC: Histologically confirmed adenocarcinoma of the colon/rectum Stage IV disease MSS-CRC status by an FDA approved test Disease progression with no more than 3 prior lines of treatment including fluroropyrimidines, irinotecan, and oxaliplatin For Triplet combination ovarian cancer: Advanced epithelial ovarian, fallopian tube, or primary peritoneal carcinoma Platinum resistant ovarian cancer (PROC) defined as disease recurrence < 6 months after completion of a platinum-containing regimen: Patients with primary platinum refractory disease are ineligible. Primary platinum refractory disease is defined as progression of disease prior to completion of 1st line platinum therapy or immediately following (≤ 3 months following last date of chemotherapy) Received ≤3 prior lines for PROC; maintenance bevacizumab or PARP are not included as a line of therapy Subjects who have received PARP inhibitor therapy are eligible Key Exclusion Criteria: Prior treatment with a TIGIT inhibitor. Prior treatment with an inhibitor of PVRIG Symptomatic interstitial lung disease or inflammatory pneumonitis. History of immune-related events that required immunotherapy treatment discontinuation For Triplet combination expansion cohorts (MSS-CRC and PROC): Prior treatment with an anti-PD-1/PD-L1/2, anti-CD96 antibody, anti-OX-40 antibody, anti-CD137 antibody, anti-LAG3, anti-TIM3, anti-CTLA4 antibody.