Combo results may offer route back to approval for Agenus' unlucky cervical cancer drug

Fifteen months after the FDA blindsided Agenus with a decision not to offer accelerated approval for the cervical cancer drug balstilimab, the biotech is back with fresh data for a combo featuring the therapy it claims could finally make headway.

The phase 1b study saw 70 patients with refractory metastatic microsatellite stable colorectal cancer (CRC) receive 3 mg of the anti-PD-1 drug every three weeks as well as 1 mg/kg or 2 mg/kg of Agenus’ anti-CTLA-4 botensilimab every six weeks. The patients, who were heavily pre-treated, experienced an overall response rate of 23% and disease control rate of 76%, the company said.

Other PD-(L)1 and CTLA-4 combinations in comparable patient populations have reported response rates of between 1% and 5%, the company noted. Presenting the data at the American Society of Clinical Oncology – Gastrointestinal Cancers Symposium on Saturday, Agenus also drew attention to a 12-month survival rate of 63%, which it compared to a rate among patients on standard of care of closer to 25%.

“This data highlights the deep and durable responses achieved with botensilimab and balstilimab in advanced MSS CRC, underscoring remarkable benefit for these patients who have failed standard of care or other investigative therapies,” said Agenus Chief Medical Officer Steven O’Day, M.D. in a release. “With over 300 patients enrolled to date, botensilimab alone and in combination with balstilimab have demonstrated durable clinical responses across nine cold and treatment-resistant cancers.”

While it may be a relatively small patient population and an early-stage trial, Agenus already has phase 2 trials on the go for the combo in CRC and solid tumors. A late-stage study in CRC is also due to go live this year, the company pointed out.

It marks a revival in the flagging fortunes of balstilimab, which at one point looked set for approval. However, the biotech pulled the application in October 2021 after Merck’s blockbuster Keytruda beat the rival checkpoint inhibitor to get the FDA’s attention in the same indication leading to some consternation from Agenus’ execs.

While the company dropped its related trial, the combo studies went on. As well as testing the therapy in combo with botensilimab, a phase 2 trial is ongoing with balstilimab and Agenus' anti-CTLA-4 zalifrelimab in cervical cancer.