Agenus Begins Rolling Submission of Balstilimab to FDA for Advanced Cervical Cancer

Agenus Begins Rolling Submission of Balstilimab to FDA for Advanced Cervical Cancer

Agenus is seeking U.S. approval of balstilimab, its investigational immunotherapy for the treatment of recurrent or metastatic cervical cancer, which has limited effective treatment options and disproportionately affects younger people.

The company has begun a rolling submission of a biologics license application (BLA) to the U.S. Food and Drug Administration (FDA). This means it will submit individual sections of the application as soon as each one is completed, rather than waiting to submit the entire document at once, as is typical.

This process is made possible due to balstilimab’s placement in the FDA’s fast track program for advanced metastatic cervical cancer.

“The initiation of the rolling BLA is an exciting step forward for Agenus as we are closer to making our therapies commercially available for patients with cervical cancer who have limited treatment options available,” Jennifer Buell, PhD, president and chief operating officer of Agenus, said in a press release. “We continue to collaborate with the leading [key opinion leaders] and the FDA in our efforts to make these treatments available to patients.”

The rolling submission is based on data from an ongoing Phase 2 clinical trial (NCT03894215), which has shown promising response rates among people with advanced cervical cancer receiving balstilimab alone.

Updated data from the trial were recently presented at the European Society for Medical Oncology Virtual Congress by David O’Malley, MD, a professor at The Ohio State University, in a presentation titled, “Single-agent anti-PD-1 balstilimab or in combination with anti-CTLA-4 zalifrelimab for recurrent/metastatic (R/M) cervical cancer (CC): Preliminary results of two independent phase II trials.”

The immune system has the capacity to kill cancer cells; however, when tumors develop, the cancer cells usually evolve strategies for avoiding immune-mediated destruction. One of the more common strategies is for cancer cells to overproduce checkpoint molecules — signaling molecules that tell the immune system not to attack.

One of the best-known checkpoint molecules is PD-L1, which binds to a receptor on immune cells called PD-1. Balstilimab is an antibody therapy designed to block PD-1 and prevent this interaction, thus allowing the immune system to more effectively destroy cancer cells.

The new data come from two recently completed clinical trials of balstilimab in people with recurrent or metastatic cervical cancer — cervical cancer that has reappeared after treatment or spread elsewhere in the body — who had previously received platinum-based chemotherapy as their first line of therapy. Both trials were funded by Agenus.

In a Phase 1/2 trial (NCT03104699), 161 participants were treated with balstilimab alone. In another Phase 1/2 trial (NCT03495882), 155 participants were treated with both balstilimab and zalifrelimab, an investigational immunotherapy that works by blocking another checkpoint molecule called CTLA4.

In both trials, the average participant age was about 50 years, and about half of the participants had PD-L1-positive tumors.

Results showed that 14% receiving balstilimab alone and 22% of those given the combination responded to treatment — meaning their cancer decreased meaningfully in size after therapy.

In both trials, response rates were better among those with PD-L1-positive tumors: 19% vs. 10% in the balstilimab only group; and 27% vs. 11% in the combination trial.

While the median response duration was 15.4 months with balstilimab alone, that measure could not yet be calculated in the combination trial after a median follow-up of 12 months (because most participants were still responding at that time).

The treatment was generally well tolerated. The rate of treatment-related immune disorders (e.g., gastrointestinal disorders and laboratory test abnormalities) was greater on the combination than on balstilimab alone.

“Balstilimab has shown activity in both PD-L1 positive and negative tumors,” Garo Armen, PhD, chairman and CEO of Agenus, in another press release. “Furthermore, we have also shown important expansion in response rates, to near doubling in PD-L1 positive patients, and durability of response when patients receive zalifrelimab in combination with balstilimab.”

The company also has plans to file another BLA seeking approval of balstilimab in combination with zalifrelimab as a second-line treatment of advanced cervical cancer that responded poorly to platinum chemotherapy.

“These trials represent the largest trials of immuno-oncology therapies in relapsed cervical cancer to date and show that balstilimab and zalifrelimab may present meaningful new therapies for patients with cervical cancer,” O’Malley said. “Advances in these agents offer renewed hope for patients who have limited treatment options.”