Agenus is now looking for alternative pathways to initiate a Phase III trial for BOT/BAL, including exploring partnerships.
Agenus revealed Thursday that the FDA has “advised against” applying for accelerated approval for its investigational immunotherapy combination regimen consisting of botensilimab and balstilimab for the treatment of a specific subtype of relapsed or refractory colorectal cancer.
The regulator made its recommendation during an end-of-Phase II meeting, where Agenus presented interim mid-stage data for the botensilimab (BOT) and balstilimab (BAL) combo. At a 75-mg BOT dose, paired with 240 mg of BAL, Agenus’ investigational regimen elicited an overall response rate of 19.4% over an average follow-up of 9.5 months.
When the BOT dose was hiked to 150 mg, ORR dropped to 8.2%. BOT monotherapy at either 75 mg or standard of care resulted in a 0% ORR.
“These results are particularly meaningful, as the landscape of MSS colorectal cancer treatment has seen little advancement leaving a significant gap in effective therapies for patients,” according to the company’s news release. Despite this promising performance, the FDA discouraged Agenus from seeking accelerated approval for BOT/BAL, noting that ORR “may not translate to survival benefit.”
Given the FDA’s position, Agenus is now seeking potential alternative pathways to make BOT/BAL available to patients. “This includes exploring opportunities to partner in the U.S. to accomplish a successful Phase III trial,” Chief Medical Officer Steven O’Day said in a statement.
As of the end of March 2024, Agenus had $52.9 million in cash and cash equivalents, which it can use to support the development of BOT/BAL, according to its first-quarter 2024 financial report. The biotech has also secured a $100 million royalty financing agreement with Ligand Pharmaceuticals, which is meant to support the confirmatory Phase III study of the combo regimen, as well as launch preparations.
However, in an interview with Endpoints News, CEO Garo Armen said the company “cannot justify, without near-term commercialization revenue coming in, funding a full-fledged Phase III trial that will yield commercialization in three or four years in the absence of an accelerated approval pathway.”
BOT is a human monoclonal antibody that works by blocking the CTLA-4 protein, in turn enhancing both the innate and adaptive immune responses against cancer. The therapy is specifically designed to also elicit therapeutic benefits for so-called cold tumors, which have suboptimal responses to standard of care or are refractory to conventional PD-1 therapies.
Meanwhile, BAL is a PD-1 blocker that complements BOT’s mechanism of action by restoring the ability of T cells to fight cancer. According to Agenus’ website, preclinical data indicate that it might have a broader spectrum of action compared with Merck’s Keytruda, leading to stronger anti-cancer activity against PD-L1-negative tumors.
In October 2021, Agenus withdrew its application for BAL—which it was proposing as a treatment for cervical cancer—after the FDA recommended that it do so. The regulator had granted Keytruda full approval in the same indication a few days earlier.
