On April 27, 2020 Compugen Ltd. (Nasdaq: CGEN), a clinical-stage cancer immunotherapy company and a leader in predictive target discovery, reported that results from its ongoing Phase 1 dose escalation study of COM701, a first-in-class anti-PVRIG antibody, in patients with advanced solid tumors who have exhausted all available standard therapies, at the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting I, today at 11:45 am EDT (Press release, Compugen, APR 27, 2020, View Source [SID1234556615]).

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COM701 was well-tolerated with no dose-limiting toxicities observed as a monotherapy and in combination with Opdivo (nivolumab). Furthermore, COM701 demonstrated encouraging signals of anti-tumor activity with high disease control rate in both the monotherapy and combination therapy arms (69% and 75%, respectively), including two confirmed partial responses and durable responses of over six months across cohorts, in the heavily pretreated patients enrolled in the study.

"I am highly encouraged by the safety profile and preliminary anti-tumor activity observed with COM701 both as a monotherapy and in combination with nivolumab," said Ryan J. Sullivan, M.D., Assistant Professor, Medicine, Harvard Medical School and Faculty Member of the Termeer Center for Targeted Therapy and Immunotherapy Programs at Massachusetts General Hospital Cancer Center, and presenting author. "With a highly refractory and all comer patient population, this trial enrolled patients that are difficult to treat including those who progressed on numerous prior therapies. Achieving durable disease control, including partial responses, is remarkable in this population and I am particularly enthusiastic about the proportion of patients in the combination arm, currently 50%, who remain on treatment. Taken together, these results support further investigation of targeting PVRIG with COM701 and suggest that targeting the PVRIG/TIGIT pathways may broaden the patient population that can benefit from immunotherapies."

Anat Cohen-Dayag, Ph.D., President and CEO of Compugen, said, "We are thrilled to see durable responses in patients with extremely challenging cancer types with poor prognosis. These findings from the completed monotherapy dose escalation and ongoing combination dose escalation study arms continue to support the potential of COM701 as a monotherapy and in combination with nivolumab in patients who have exhausted all available treatment options. Notably, the ongoing responses in microsatellite stable colorectal cancer and primary peritoneal cancer, a type of ovarian cancer, are supportive of our biomarker-informed selection of indications for the monotherapy expansion cohorts."

The reported data are from the monotherapy and combination arms of the ongoing, Phase 1, open label, dose escalation study and include all eight cohorts from the monotherapy arm (n=16), and the first three of four cohorts of the combination arm (n=12).

Key findings to be presented by Dr. Sullivan in an oral virtual presentation titled "COM701 Demonstrates Antitumor Activity as Monotherapy and in Combination with Nivolumab in Patients with Advanced Malignancies" include:

COM701 was well-tolerated through 20 mg/kg IV Q4 weeks as a monotherapy and 10 mg/kg IV Q4 weeks in combination with Opdivo (480 mg IV Q4 weeks) with no dose-limiting toxicities reported.

No increased toxicity was observed in the combination arm.

No patients discontinued treatment due to toxicity of any study drug.

Preliminary COM701 pharmacokinetic data supports IV Q4 weeks dosing, allowing dosing schedule with Opdivo.

Encouraging disease control rates of 69% (11/16) for monotherapy and 75% (9/12) for combination arm.

50% of patients (6/12) in the combination arm remain on study, some with continued responses observed beyond 200 days of treatment.

Across cohorts, durable responses of stable disease for over six months in six of 28 (21%) patients.

The two patients previously reported with confirmed partial responses, one from the monotherapy arm (microsatellite stable primary peritoneal cancer) and one from the combination arm (microsatellite stable colorectal cancer), remain on treatment.

Enrollment in the COM701 monotherapy dose escalation arm is completed and enrollment in the combination dose escalation arm at 20 mg/kg IV Q4 weeks is ongoing. The monotherapy expansion cohorts that will follow the monotherapy dose escalation arm is based on a biomarker-informed selection of indications, and will include non-small cell lung cancer, ovarian, breast, endometrial and colorectal cancer. During this monotherapy expansion study, biopsies will be collected before and on COM701 treatment to allow retrospective analyses of Compugen’s DNAM axis biomarker approach.

About the COM701 Phase 1 Study
The Phase 1 open-label clinical trial of COM701 is designed to assess the safety and tolerability of administering escalating doses of COM701 monotherapy as well as of combination administration with Bristol-Myers Squibb’s Opdivo (nivolumab) in patients with advanced solid tumors. Additionally, secondary endpoints include preliminary antitumor activity, pharmacokinetics and pharmacodynamics of COM701 monotherapy and in combination with Opdivo (nivolumab) in patients with selected tumor types, including non-small cell lung cancer, ovarian cancer, breast cancer, endometrial cancer and colorectal cancer. Additional information is available at www.clinicaltrials.gov (NCT 03667716).

About COM701
COM701 is a humanized antibody that binds with high affinity to PVRIG, a novel immune checkpoint discovered computationally by Compugen, and blocks the interaction with its ligand, PVRL2. TIGIT, discovered by Compugen’s computational discovery platform in 2009, and PVRIG constitute parallel immune checkpoint pathways that counteract DNAM, a costimulatory molecule on T cells and NK cells. Preclinical data suggest that the blockade of PVRIG induces a robust anti-tumor immune response and demonstrates synergistic activity when used in combination with inhibitors of TIGIT and/or PD-1. Currently, COM701 is being evaluated in a Phase 1 clinical study. Data from the ongoing study have shown that COM701 is well-tolerated and demonstrated preliminary signals of anti-tumor activity in a heavily pretreated patient population.