The FDA has accepted the biologics license application for the anti-PD-1 antibody drug balstilimab for the treatment of recurrent of metastatic cervical cancer with disease progression on or after chemotherapy.
The FDA has accepted the biologics license application (BLA) for the anti-PD-1 antibody drug balstilimab for the treatment of recurrent of metastatic cervical cancer with disease progression on or after chemotherapy, according to a press release by Agenus Inc.
Balstilimab, which is a fully human monoclonal immunoglobulin G4 (IgG4), prevents its ligands, PD-L1 and PD-L2, from interacting with programmed cell death protein 1 (PD-1). Additionally, the novel agent is a negative regulator or immune activation- a foundational target for the immuno-oncology space. The news of BLA acceptance comes after a December 2020 announcement that the BLA was delayed in order to solidify diagnostic requirement for PD-L1 testing.
The agent is being studied as both a monotherapy and in combination with zalifrelimab, an anti-CTLA-4 antibody for recurrent or metastatic cervical cancer. The BLA is based on data from 2 phase 2 trials presented at the 2020 European Society of Medical Oncology’s (ESMO) Virtual Congress.
The first study (NCT03104699) looked at balstilimab as a monotherapy. The study, which has an actual enrollment of 211 participants, evaluated the safety and efficacy of the agent given at 3mg/kg by IV every 2 weeks for up to 24 months. The primary outcome of the study was objective response rate (ORR). Secondary outcomes included safety and tolerability, maximum drug concentration observed post dose at steady-state, minimum observed concertation at steady-state, area under the drug concentration-time curve from time zero to time t, time to maximum observed concentration, duration of response (DoR), disease control rate (DCR), duration of stable disease, time to response, progression-free survival (PFS), and the overall survival rate (OS).
In order to participate, patients must be 18 years of age or older, have confirmed squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix, have metastatic, locally advanced, and/or unresectable disease at the time of enrollment, have relapsed disease after platinum-based treatment, have a life expectancy of at least 3 months, have adequate organ function, and have measurable disease. Patients with prior exposure to anti-PD-1 and anti-PD-L1 therapy, have an inadequate washout period prior to first dose, has a central nervous system tumor, has had an allogeneic tissue/solid organ transplant, has had or current has interstitial lung disease, or an active infection are not eligible to participate.
The second study (NCT03495882) looked at the safety and efficacy of balstilimab in combination with zalifrelimab. The study had an actual enrollment of 154 participants. During the study, patients received the two agents in combination according to protocol design. The primary outcome of the study was ORR. Secondary outcomes include safety and tolerability, maximum drug concentration, minimum observed concentration, area under the drug concentration-time curve, time to maximum observed dose, DoR, DCR, duration of stable disease, time to response, PFS, and OS.
In order to participate, patients must be 18 years of age or older, have confirmed cervical cancer, have relapsed after platinum-based chemotherapy, measurable disease, a life expectancy of at least 3 months, and adequate organ function. Patients who have had an inadequate washout period prior to first dose of the study drug, persisting toxicity related to prior therapy, has a central nervous system tumor, a history or an active autoimmune disease, has received allogenic tissue/solid organ function, or has a known history of HIV are not eligible to participate.
The ORR for patients in the combination trial was 27% compared to the 18% in the single-agent study. In the monotherapy study, the ORR was 19% for those with PD-L1 positive disease, 10% for PD-L1 negative disease, and 0% for those with unknown PD-L1 status. For the combination study, the ORRs for these groups were 17%, 11% and 21%, respectively.
During both studies, treatment was well tolerated, and no new safety signals were identified. All-grade endocrine disorders occurred at a rate of 20.6% in the combination study and 9.3% in the monotherapy study. Additionally, immune-related adverse events (AEs) occurred at a higher rate in the combination study compared to the monotherapy study. Gastrointestinal disorders, for example, occurred in 8.4% of those in the combination study and 5.6% in the monotherapy study. Laboratory abnormalities occurred in 11.6% of patients in the combination study versus 5.6% in the monotherapy study, and endocrine disorders occurred in 18.7% of the patients enrolled in the combination study compared to 5% in the monotherapy study.
The BLA for the agent was granted priority review and it has a Prescription Drug User Fee Act target action date of December 16, 2021.