AACR: Compugen's checkpoint inhibitor keeps cancer in check

Although Compugen tested COM701 in a variety of different tumors, it is developing the drug with an eye on tumors that express high levels of PVRIG, an immune checkpoint, and the protein it binds to, PVRL2. (Compugen)

Compugen’s anti-PVRIG antibody showed early promise in a small phase 1 study, curbing tumor growth in more than two-thirds of patients with various solid tumors who had exhausted all other treatment options. The treatment did similarly in tandem with Bristol Myers Squibb’s PD-1 blocker Opdivo, stopping tumor growth in three-quarters of patients.

The results come from a group of 28 patients who received varying dose levels of Compugen’s drug, COM701, ranging from 0.1 mg per kilogram of bodyweight to 20 mg/kg. Sixteen patients received the drug on its own, while 12 patients received it in combination with Opdivo. To be presented at the first virtual session of this year’s American Association for Cancer Research annual meeting, the data included two patients whose tumors shrank. One of those patients had a type of ovarian cancer and received COM701 on its own, while the other had colorectal cancer and received the Opdivo combination.

The study was small and focused on gauging the safety of COM701 alone, as well as in combination with Opdivo, but the early efficacy results are promising, especially in a group of patients who have run out of treatment options, including other experimental drugs.

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“We are talking about patients with relapsed disease who have no other options. They’ve exhausted everything,” Compugen Chief Medical Officer Henry Adewoye, M.D., told FierceBiotech, adding that some of the patients had tried as many as 15 prior treatments.

RELATED: Compugen cuts 35% of workforce to push cash runway into mid-2020

Although Compugen tested COM701 in a variety of different tumors, it is developing the drug with an eye on tumors that express high levels of PVRIG, an immune checkpoint, and the protein it binds to, PVRL2.

“Most of the patients are not in the patient population we previously selected based on expression of the biomarker that is of interest to us,” Adewoye said, referring to PVRL2. Compugen expects the drug to do even better in that patient group.

“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,” said Ryan Sullivan, M.D., a professor at Harvard Medical School who will present the study. “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.”

RELATED: Bristol-Myers, Compugen ally to test checkpoint combinations

Although checkpoint inhibitors have seen success in certain cancers, they don’t work for everyone. Compugen’s pipeline is based on the understanding that multiple pathways can drive cancer in the same patient: “There is now scientific literature that the PD-1 pathway—the current target of cancer immunotherapy—has a molecular intersection with PVRIG and TIGIT. We see this as a three-pathway story,” Compugen CEO Anat Cohen-Dayag, Ph.D., told FierceBiotech.

Compugen figures that PD-1 inhibitors like Opdivo work in cancers where the PD-1 pathway is dominant and other pathways’ contributions are smaller. Patients whose cancer isn’t affected by PD-1 blockade may need the other pathways to be released, Cohen-Dayag said. That’s where drugs targeting PVRIG and TIGIT come in.

In addition to testing COM701 alone and in combination with Opdivo, Compugen and BMS will also test a triple therapy, which includes the COM701-Opdivo combo and BMS’ experimental TIGIT blocker. That study, which will enroll patients with high levels of PVRL2, will kick off in the second half of 2020.

As for the current study, Compugen will expand the monotherapy patient group to include patients whose cancers have high levels of PVRL2, including non-small cell lung, ovarian, breast and endometrial cancers. But it will also enroll patients with lower levels of the protein so it can pinpoint a threshold of expression with respect to response, Cohen-Dayag said.

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