COM902 (A TIGIT Inhibitor) in Subjects With Advanced Malignancies

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1 Study of The Safety and Tolerability of COM902 in Subjects With Advanced Malignancies

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

Intervention / Treatment
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* Drug: Dose escalation: COM902 monotherapy.
* Combination Product: Evaluation of safety/tolerability: COM902 in combination with COM701 (both at the RDFE)
* Drug: Cohort expansion: COM902 (RDFE) monotherapy.
* Drug: Cohort expansion: COM902 in combination with COM701 (both at the RDFE).
* Combination Product: Cohort expansion: Triplet combination of COM902 + COM701 + Pembrolizumab.


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COM902 monotherapy dose escalation.<br>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. | Drug: Dose escalation: COM902 monotherapy.<br>* COM902 monotherapy administered IV every 3 weeks in sequential dose escalation doses in cohorts of subjects.<br>|
| Experimental: Dual combination (COM902 + COM701) for evaluation of safety/tolerability (both at RDFE).<br>COM902 will be combined with COM701 for evaluation of safety and tolerability. All study drugs will be administered IV every 3 weeks. | Combination Product: Evaluation of safety/tolerability: COM902 in combination with COM701 (both at the RDFE)<br>* 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.<br>|
| Experimental: COM902 monotherapy cohort expansion at RDFE.<br>COM902 monotherapy at the RDFE - in subjects with multiple myeloma. COM902 will be administered IV every 3 weeks. | Drug: Cohort expansion: COM902 (RDFE) monotherapy.<br>* COM902 monotherapy (RDFE) in subjects with multiple myeloma. COM902 will be administered IV every 3 weeks.<br>|
| Experimental: COM902 + COM701 combination cohort expansion both at RDFE.<br>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. | Drug: Cohort expansion: COM902 in combination with COM701 (both at the RDFE).<br>* 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.<br>|
| Experimental: MSS-CRC Triplet combination (COM902 + COM701 + Pembrolizumab).<br>Triplet combination of COM902 + COM701 + Pembrolizumab evaluated in subjects with MSS-CRC. All study drugs will be administered IV every 3 weeks. | Combination Product: Cohort expansion: Triplet combination of COM902 + COM701 + Pembrolizumab.<br>* Triplet combination of COM902 + COM701 + Pembrolizumab administered IV every 3 weeks.<br>|
| Experimental: Platinum resistant ovarian cancer Triplet combination (COM902 + COM701 + Pembrolizumab).<br>Triplet combination of COM902 + COM701 + Pembrolizumab evaluated in subjects with PROC. All study drugs will be administered IV every 3 weeks. | Combination Product: Cohort expansion: Triplet combination of COM902 + COM701 + Pembrolizumab.<br>* Triplet combination of COM902 + COM701 + Pembrolizumab administered IV every 3 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety and tolerability of COM902 monotherapy and in combination with COM701. | Incidence of subjects with Adverse Events (AEs) as per CTCAE v5.0 and Dose-Limiting Toxicities (DLTs). | DLT evaluation window in the 1st cycle (21 Days). | 
| 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. | 18 months. | 
| 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]). | 18 months. | 
| Evaluation of safety and tolerability of the Triplet combination (COM902 + COM701 + Pembrolizumab). | Incidence of subjects on the Triplet combination (COM902 + COM701 + Pembrolizumab) with Adverse Events (AEs) per CTCAE v5.0. | 18 months. | 
| Evaluation of the PK profile of the Triplet combination (COM902 + COM701 + Pembrolizumab). | Evaluation of PK parameters e.g., Cmax. | 18 months. | 
| Evaluation of the PK profile of the Triplet combination (COM902 + COM701 + Pembrolizumab). | Evaluation of PK parameters e.g., AUC. | 18 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To characterize immunogenicity of COM902 monotherapy and in combination with COM701. | Evaluation of anti drug antibody to COM902 (monotherapy) or COM902, COM701 when administered in combination. | 18 months. | 
| To characterize the immunogenicity of the Triplet combination (COM902 + COM701 + Pembrolizumab). | Evaluation of antidrug antibody to COM902, COM701. | 18 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TIGIT antibody, PVRIG antibody, COM701, Low Fc-effector function, Pembrolizumab