Well-tolerated tumor drug

HOLON, Israel—Compugen Ltd., a clinical-stage cancer immunotherapy company specializing in predictive target discovery, presented updated results from its ongoing Phase 1 dose-escalation study of COM701 at the 2020 American Association for Cancer Research (AACR) Virtual Annual Meeting I in April. COM701 is a first-in-class anti-PVRIG antibody being evaluated in patients with advanced solid tumors who have exhausted all available standard therapies. Compugen is attempting to establish a predictive drug discovery infrastructure and to discover and develop novel therapeutic proteins and drug targets.

Demonstrating what the company called “encouraging signals of durable disease control,” COM701 was well tolerated with no dose-limiting toxicities observed, both as a monotherapy and in combination with Bristol-Myers Squibb’s Opdivo (nivolumab). Additionally, COM701 demonstrated promising signs of anti-tumor activity with high disease control rate in both the monotherapy and combination therapy arms (69 percent and 75 percent, respectively). Those figures included two confirmed partial responses and durable responses of more than six months across cohorts, in the heavily pretreated patients enrolled in the study.

Key findings presented by Dr. Ryan J. Sullivan, assistant professor of Medicine at Harvard Medical School and faculty member of the Termeer Center for Targeted Therapy and Immunotherapy Programs at Massachusetts General Hospital Cancer, showed that 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). No dose-limiting toxicities were reported, no increased toxicity was observed in the combination arm, and no patients discontinued treatment because of the toxicity of any study drug. Sullivan said that preliminary COM701 pharmacokinetic data supports IV Q4 weeks dosing, allowing the dosing schedule with Opdivo.

Half of the patients (six of 12) in the combination arm remain on study, some with continued responses observed beyond 200 days of treatment. Across cohorts, there were durable responses of stable disease for over six months in six of 28 (21 percent) 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.

As Sullivan commented in his presentation, “There is a high unmet medical need for the treatment of patients who are refractory to or relapse following treatment with checkpoint inhibitors. COM701 is a novel first-in-class humanized IgG4 monoclonal antibody that binds with high-affinity PVRIG, a novel immune checkpoint discovered computationally by Compugen, blocking its interaction with its ligand PVRL2. We have previously reported on the preliminary antitumor activity of COM701 monotherapy. We are now reporting the preliminary safety and antitumor activity of COM701 in combination with nivolumab (Arm B), and we provide data update in COM701 monotherapy dose cohorts (Arm A).”

“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,” he added. “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 percent—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.”

According to Dr. Anat Cohen-Dayag, president and CEO of Compugen, “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.”

“COM701 proved to be well tolerated and with a manageable safety profile as monotherapy and in combination with nivolumab. Currently, 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,” Sullivan concluded.