The U.S. Food and Drug Administration (FDA) has now given fast track status to Agenus’ balstilimab — both alone and in combination — as an immunotherapy candidate for advanced metastatic cervical cancer.
This designation, given separately to these different treatment approaches, is meant to help speed its development by facilitating discussions with the FDA and enabling the therapy to qualify for priority review and accelerated approval, provided certain criteria are met.
The company plans to file two biologics license applications (BLAs) seeking approval of balstilimab alone and in combination with zalifrelimab as a second-line treatment of advanced cervical cancer that responded poorly to platinum chemotherapy.
“We are pleased to have now been granted Fast Track designation by FDA for both balstilimab as a monotherapy and in combination with zalifrelimab … in recognition of the high unmet medical need in second line cervical cancer,” Anna Wijatyk, head of clinical development at Agenus, said in a press release.
“[W]e are excited to work with the FDA to quickly advance novel agents for women who suffer from metastatic cervical cancer,” she added.
The FDA’s decision was supported by early data from an ongoing Phase 2 clinical trial (NCT03894215). This study is assessing the effectiveness and safety of balstilimab alone or in combination with zalifrelimab as a second-line therapy for women whose cervical cancer relapsed or worsened after first-line platinum-based chemotherapy.
The trial may be recruiting eligible patients at sites across in the U.S.; many trials are on temporary hold during ongoing COVID-19 pandemic, however. Those interested in taking part can learn more by contacting a coordinator at a site of their choice.
Participants are being treated for a maximum of 24 months, or until disease progression or unacceptable toxicity.
Updated data showed robust and durable activity for balstilimab combined with zalifrelimab. The group given both therapies had a 26.5% objective response rate (ORR), meaning either complete (four patients) or partial reduction (five) in tumor size over 50 weeks of treatment. Those given balstilimab as monotherapy showed a lower ORR (14.3%), including one complete and five partial responses.
Balstilimab (previously called AGEN2034) and zalifrelimab (previously AGEN1884) are investigational anticancer therapies, called immune checkpoint inhibitors.
Balstilimab blocks the activity of the protein PD-1, while zalifrelimab blocks CTLA-4. PD-1 and CTLA-4, found in healthy cells, act as an “off switch” in T-cells to prevent immune attack.
But cancer cells have taken advantage of this process to evade immune defenses. When PD-1 or CTLA-4 bind to proteins on immune or cancer cells — such as PD-L1 and CD80 — T-cells are not able to kill the tumor cells.
By targeting these interactions, balstilimab and zalifrelimab are intended to boost the immune system’s ability to fight cancer.
This treatment combination is also being tested in a Phase 1/2 clinical trial (NCT03495882) in people with advanced solid tumors. Phase 1 is tested escalating doses to determine the dose for the study’s Phase 2, which is examining tumor response in patients, and plans to include a group with advanced cervical cancer.
Phase 2 may still be recruiting advanced cervical and other cancer patients at sites across the U.S., Europe, Australia and Brazil; more information is available here. But again, the pandemic may require changes in the interest of safety.
