Treatment with Compugen‘s immune checkpoint inhibitor COM701, either alone or in combination with Opdivo (nivolumab), is well-tolerated in people with advanced solid tumors, including ovarian cancer, early Phase 1 trial results show.
The findings were presented in a poster, “A Phase 1 Study Evaluating COM701 Monotherapy and in Combination with Nivolumab in Patients With Advanced Solid Malignancies,” at the recent ASCO-SITC Clinical Immuno-Oncology Symposium in Orlando, Florida.
Immune checkpoint proteins tell the immune system what is normal and what is abnormal. Cancer cells, however, hijack this checkpoint system and produce proteins that bind to the checkpoint receptors found on immune cells and deactivate them.
Several inhibitors of these checkpoint molecules are approved for cancer treatment, including the PD-1 inhibitors Keytruda (pembrolizumab) and Opdivo (nivolumab), the PD-L1 inhibitors Tecentriq (atezolizumab) and Imfinzi (durvalumab), and the CTLA-4 inhibitor Yervoy (ipilimumab).
Using its computational predictive platform, Compugen identified a novel target, called PVRIG, for immune checkpoint therapies. This receptor is found on the surface of T-cells that infiltrate cancers, and binds to PVRL2, which is produced by many cancers, including ovarian cancer.
COM701 is a first-in-class antibody against PVRIG that has been shown to inhibit its binding to PVRL2 in animal models, resulting in robust T-cell activation and reduced tumor growth. The study also suggested that COM701’s anti-tumor effect is even stronger when combined with a PD-1 inhibitor, such as Bristol-Myers Squibb‘s Opdivo.
The findings led Compugen and Bristol-Myers to collaborate on a clinical trial to evaluate the safety and preliminary signs of efficacy of COM701, alone and in combination with Opdivo, in a broad population of patients with advanced solid tumors.
The open-label Phase 1 trial (NCT03667716) aims to recruit 140 participants with cancers of the ovary, breast, lung, and endometrium, among others. It is enrolling at multiple sites in the United States.
The trial is being conducted in two parts. First, patients will receive increasing doses of COM701 intravenously (into the vein) every three or four weeks, either as a single therapy or in combination with intravenous Opdivo (given at a dose of 360 mg every three weeks or 480 mg every four weeks).
Up to eight different dose groups may be tested, either until a maximum tolerated dose is reached or an optimal dose is identified.
The second part of the trial is a dose expansion study, in which the optimal dose of COM701, alone or in combination with Opdivo, will be tested in patients with select tumour types, including ovarian, breast, endometrial, and non-small cell lung cancer.
The trial’s main goals are to assess the safety, tolerability, and pharmacokinetics (how it is absorbed, distributed, metabolized, and eliminated) of COM701 alone, and with Opdivo. Secondary measures include the treatment’s pharmacodynamics (how it affects the body), and preliminary signs of efficacy in the select cancers included in part 2.
Researchers have now reported that COM701 alone is well-tolerated through the 10 mg/kg dose, with no patient experiencing any dose-limiting toxicity. Enrolment for the eighth dose level (20 mg/kg every four weeks) in the single therapy group is ongoing.
Furthermore, enrolment has been completed in the fourth dose level (with treatment every four weeks) in the combination treatment group. No dose-limiting toxicities were identified in this group.
To date, 13 patients have been included in the trial. This was a heavily pretreated population, with a median of seven prior lines of therapy. The researchers have reported preliminary signs of anti-tumor efficacy, with 69% of these patients achieving at least stable disease.
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