This is an edited version of an article by Ryan Scott published in OncLive Jan. 12, 2023
A triplet regimen comprised of COM701, BMS-986207, and nivolumab (Opdivo) was found to have encouraging antitumor activity and favorable tolerability in patients with heavily pretreated, platinum-resistant ovarian cancer, according to data from a phase 1/2 trial (NCT04570839) presented at the 2022 ESMO Immuno-Oncology Annual Congress.
COM701 is a novel, first-in-class, immune checkpoint inhibitor–blocker that binds to PVRIG. It has demonstrated preliminary antitumor activity when utilized as a single agent or when combined with nivolumab in patients with this disease. Investigators hypothesized that triple blockade comprised of PVRIG, TIGIT, and PD-1 would have activity in this population and be well tolerated.
In this Phase-1 trial, the key primary objective of the research was to evaluate the safety and tolerability of the regimen, and a key secondary objective was to examine antitumor activity…
“This was a standard phase 1 design, with a focus toward evaluating the safety and early efficacy of the combination,” lead study author John Moroney, M.D. noted. “First-in-human and first combination trials [of COM701] have already, for the most part, been done. This [investigation] was also done in parallel with a doublet trial [NCT04354246], evaluating the combination of COM701 with another TIGIT inhibitor [COM902].”
Of the 20 patients enrolled to the trial, 50% were aged 65 years or older, and 70% had an ECOG performance status of 1. [Note: ECOG is the Eastern Cooperative Oncology
Group Performance Status. An ECOG status of 1 refers to patients who are fully ambulatory and able to carry out light work, capable of all self-care, but strenuous physical activity is restricted].
Of the 20 patients enrolled, histology was recorded as: 55% of patients had high-grade serous disease, 15% had clear cell disease, and 30% did not have this information available. Moreover, 80% of patients previously received a bevacizumab (Avastin)-containing regimen, and 30% had prior exposure to a PARP inhibitor…. The median number of prior lines of therapy was 4…
“We had impressive responses in heavily pretreated patients,” lead study author John Moroney, MD, said during an interview with OncLive®. “Of the 20 patients who received this drug, there were 4 confirmed durable and deep responses. It was exciting in an ovarian cancer [setting] to see that at all.”
Eighty percent of patients discontinued study treatment. Reasons for discontinuation included progressive disease by RECIST v1.1 criteria (75%) or an adverse effect (AE; 5%).
Regarding safety, 55% of the patients evaluated experienced any-grade treatment-related AEs (TRAEs). Twenty percent of patients experienced a TRAE that was grade 2 or lower, and 35% had a grade 3 TRAE; no grade 4 AEs were observed.
“Historically, among different trials with immune checkpoint inhibition in ovarian cancer, the number and percentage of severe AEs was extremely low, and [the combination] was well tolerated,” Moroney said.
Additional translational research is ongoing, but investigators concluded that further investigation is warranted.
“It is hoped that with enough thoughtful investigation, we will identify good biomarkers to find who the responders are in advance,” Moroney concluded.