Compugen and BMS Launch New Triple Combination Therapy for Advanced Tumors Interview with:

Anat Cohen-Dayag, Ph.D.
President and CEO
Compugen What is the background for this announcement? Would you discuss Compugen’s underlying cancer hypothesis regarding the targeting of multiple checkpoint pathways to enhance tumor response?

Response: Cancer immunotherapy has revolutionized the landscape for cancer treatments by providing new drug options leading to lasting benefits for patients. Yet, response rates vary greatly across different cancer indications, leaving a significant unmet medical need for many patients and a continuing challenge to discover new biological pathways that can serve for the development of new cancer immunotherapies for non-responsive and refractory patients.

Using a computational approach which is designed to discover new biological pathways and drug targets, we identified PVRIG as a novel immune checkpoint and a newly discovered inhibitory pathway in the DNAM axis. Our hypothesis is that PVRIG and TIGIT (another inhibitory pathway discovered by us and others) are two parallel and complementary inhibitory pathways in the DNAM axis and that in certain tumor types and patient populations, there may be a need to block both PVRIG and TIGIT in order to enhance anti-tumor immune responses. Moreover, reported molecular intersections between the DNAM axis and the PD-1 pathway, the most prevalent pathway targeted by approved immunotherapies, suggest that there is a linkage between these three pathways. As such, our PVRIG inhibitor may work in synergy with PD-1 and TIGIT inhibitors, suggesting that various drug combinations may be required to address these three pathways based on their dominance in different cancer patients and cancer indications. With this recently announced Phase 1/2 triple combination study, we will be directly testing our hypothesis of an intersection between the three parallel immune checkpoint pathways – PVRIG, TIGIT and PD-1 – and that the simultaneous blockade of these pathways has the potential to synergistically enhance anti-tumor immune response and expand the reach of cancer immunotherapy to patients non-responsive or refractory to approved immunotherapies. What are the main findings of the Phase 1 monotherapy trial of COM701?

Response: In our Phase 1 monotherapy trial we are exploring the potential of COM701, an anti-PVRIG antibody, in patients with advanced solid tumors who have exhausted standard of care treatment. Patients in this trial were heavily pretreated with anticancer therapies, receiving a median of 7 prior therapies that failed. Having seen signals of antitumor activity in the dose escalation portion of the study is highly encouraging. Specifically, nine of the 13 patients enrolled in the dose escalation study had a best timepoint antitumor activity of stable disease. Moreover, of those 13 patients, six had MSS-colorectal cancer, a notoriously difficult cancer to treat. For the MSS-CRC patients – we reported a best timepoint antitumor activity of stable disease in five out of six patients.

Upon completion of dose escalation study, we look forward to beginning a biomarker-driven COM701 monotherapy cohort expansion in patients with advanced non-small cell lung, ovarian, breast, endometrial, and colorectal cancer. This selection of cancer indications which we believe patients are more likely to respond to COM701 treatment is based on expression profile data of the various axis members and the initial clinical data we reported. How will the partnership with BMS enhance/expedite this research?

Response: In addition to strategic insight as a leader in the immuno-oncology space, BMS is providing Compugen its approved PD-1 inhibitor Opdivo® and investigational TIGIT inhibitor, BMS-986207 which allows us to move directly into testing our central hypothesis in a triple combination study. Ultimately, this triple combination study will accelerate the development of a potentially new powerful therapeutics for the treatment of refractory and resistant cancers. What should readers take away from your report? 

Response: We are very proud of our computational target discovery capabilities with which we discovered, to date, three new biological pathways that are now being evaluated in the clinic. COM701, an immuno-oncology therapeutic antibody, which targets the PVRIG pathway, a novel therapeutic target we discovered computationally, has the potential to serve as a first-in-class cancer immunotherapy drug. This follows our discovery of the TIGIT pathway which we published in 2009, and which now appears to be clinically validated by others. These two pathways and our suggested linkage between PVRIG, TIGIT and PD-1 pathways will be evaluated in this new Phase 1/2 triple combination trial and accelerate our clinical development of COM701. Is there anything else you would like to add?

Response: There is a large unmet need for patients with cancer, with a majority of cancers still being untreatable using approved immunotherapies. Through the identification of new potential drug target opportunities to improve the response rate to cancer therapies, we believe we can develop therapeutic strategies that are more effective in a broader patient population. This new Phase 1/2 triple combination trial represents the next step in our efforts to do so. We are uniquely positioned to evaluate the full potential of the DNAM axis, which is receiving growing attention in the pharma industry given that, to our knowledge, we are the only company with a clinical program targeting PVRIG.


Compugen and Bristol-Myers Squibb will initiate a Phase 1/2 triple combination clinical trial in advanced solid tumors.
Compugen Announces Phase 1/2 Triple Combination Study to Evaluate COM701 in Combination With Bristol-Myers Squibb’s Opdivo® (Nivolumab) and TIGIT Inhibitor
Published: Feb 20, 2020


Last Modified: Mar 19, 2020 @ 7:38 pm

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