COM701 shows antitumor activity in advanced solid tumors
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COM701, a novel first-in-class immune checkpoint inhibitor, demonstrated antitumor activity alone and in combination with nivolumab among patients with advanced solid tumors, according to results of a phase 1 study presented at the virtual American Association for Cancer Research Annual Meeting.
The agent also induced objective responses with and without nivolumab (Opdivo, Bristol-Myers Squibb) in difficult-to-treat tumor types, such as primary peritoneal and microsatellite stable colorectal cancer.
“Remarkable advances in antitumor activity have been made during the past several years. However, a critical unmet need remains for the treatment of patients who are refractory to or relapse following treatment with checkpoint inhibitors,” Ryan J. Sullivan, MD, assistant professor in the department of hematology/oncology at Massachusetts General Hospital, said during the presentation. “We have previously reported on the preliminary antitumor activity of COM701 [Compugen] monotherapy, but we are now reporting the preliminary safety and antitumor activity of the agent in combination with nivolumab.”
COM701 binds with high affinity to poliovirus receptor-associated immunoglobulin domain containing (PVRIG), blocking its interaction with its ligand, PVRL2, and regulates the activity of T cells and natural killer cells through the DNAM/TIGIT axis.
PVRIG blockade induces a robust antitumor immune response and shows synergistic activity when used in combination with inhibitors of TIGIT and/or PD-1, according to a press release issued by Compugen prior to the presentation.
Sullivan and colleagues enrolled 28 patients with advanced solid tumors and an ECOG status of 0 to 1 who failed previous standard of care therapy. Researchers administered COM701 alone in doses ranging from 0.01 mg/kg to 10 mg/kg every 3 weeks or 20 mg/kg every 4 weeks (Arm A, n = 16) compared with COM701 in doses ranging from 0.3 mg/kg to 3 mg/kg plus 360 mg nivolumab every 3 weeks, or 10 mg/kg COM701 plus 480 mg nivolumab every 4 weeks (Arm B, n = 12).
Median number of prior anticancer therapies was six (range, 2-15) in Arm A and four (range, 2-12) in Arm B.
At the time of data cutoff, eight patients remained on treatment, including three patients who had not reached first imaging assessment. No dose-limiting toxicities had been reported among any of the cohorts.
Results showed partial responses in two patients in both arms combined. In addition, stable disease was achieved among six patients and the disease control rate was 69% in Arm A and 75% in Arm B.
The most common grade 1 to grade 2 treatment-related adverse events in Arm A included fatigue (39%), nausea (28%), anxiety (22%) and diarrhea (17%). Common grade 1 to grade 2 adverse events in Arm B included fatigue (39%), anemia (23%), constipation (23%) and nausea (15%).
“Based upon the promising preclinical data and the data from the current study, a phase 1/2 trial is in development, which includes a triple combination,” Sullivan said. – by Jennifer Southall
Reference:
Sullivan R, et al. Abstract CT031. Presented at: AACR Annual Meeting; April 27-28, 2020 (virtual meeting).
Disclosures: The study was funded by Compugen Ltd. in collaboration with Bristol-Myers Squibb. Sullivan reports consultant/advisory roles with Bristol-Myers Squibb, Merck, Novartis and Replimune; and research funding from Amgen and Merck. Please see the abstract for all other researchers’ relevant financial disclosures.