COM902 (A TIGIT Inhibitor) in Subjects With Advanced Malignancies

Conditions

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

Keywords

TIGIT antibody, PVRIG antibody, COM701, Low Fc-effector function, Pembrolizumab

Brief summary

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.

Manish Sharma, Anne M. Noonan, Daniel A. Vaena, Ecaterina E. Dumbrava, Judy S. Wang et al. (15 authors)

Journal of Clinical Oncology2024-06-011 citations

10.1200/jco.2024.42.16_suppl.3597

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Colby S. Shemesh, Yongsheng Wang, Andrew An, Hao Ding, Phyllis Chan et al. (10 authors)

Cancer Chemotherapy and Pharmacology2024-03-073 citations

10.1007/s00280-024-04650-y

Role of Next Generation Immune Checkpoint Inhibitor (ICI) Therapy in Philadelphia Negative Classic Myeloproliferative Neoplasm (MPN): Review of the Literature.

Yadav R, Hakobyan N, Wang JC.

2023-08-075 citations

10.3390/ijms241512502

Natural killer cells and bone marrow mesenchymal stem cells: A dangerous liaison in multiple myeloma

Iria Fernandez Botana, Etienne Moussay, Jérôme Paggetti

Clinical and Translational Discovery2022-07-281 citations

10.1002/ctd2.116

477 COM902 (Anti-TIGIT antibody) monotherapy – preliminary evaluation of safety, tolerability, pharmacokinetics and receptor occupancy in patients with advanced solid tumors (NCT04354246)

Ecaterina E. Dumbrava, Drew Rasco, Amita Patnaik, Daniel A. Vaena, Kyriakos P. Papadopoulos et al. (12 authors)

Regular and Young Investigator Award Abstracts2021-11-016 citations

10.1136/jitc-2021-sitc2021.477

Interventions

DRUGDose escalation: COM902 monotherapy.

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

COMBINATION_PRODUCTEvaluation of safety/tolerability: COM902 in combination with COM701 (both at the RDFE)

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.

DRUGCohort expansion: COM902 (RDFE) monotherapy.

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

DRUGCohort expansion: COM902 in combination with COM701 (both at the RDFE).

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.

COMBINATION_PRODUCTCohort expansion: Triplet combination of COM902 + COM701 + Pembrolizumab.

Triplet combination of COM902 + COM701 + Pembrolizumab administered IV every 3 weeks.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

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.

Design outcomes

Primary

Measure	Time frame	Description
The safety and tolerability of COM902 monotherapy and in combination with COM701.	DLT evaluation window in the 1st cycle (21 Days).	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.	18 months.	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.	18 months.	Evaluation of parameters of COM902 monotherapy or in combination with COM701 exposure such as Maximum Plasma Concentration \[Cmax\]).
Evaluation of safety and tolerability of the Triplet combination (COM902 + COM701 + Pembrolizumab).	18 months.	Incidence of subjects on the Triplet combination (COM902 + COM701 + Pembrolizumab) with Adverse Events (AEs) per CTCAE v5.0.
Evaluation of the PK profile of the Triplet combination (COM902 + COM701 + Pembrolizumab).	18 months.	Evaluation of PK parameters e.g., Cmax.

Secondary

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

Countries

United States

Contacts

STUDY_DIRECTORCOM902 Study Director COM902 Study Director

Compugen Ltd

Outcome results

None listed