BLA Submission Delayed for Balstilimab For Treatment of Recurrent/metastatic Cervical Cancer

The FDA pushed back its the Biologic License Application (BLA) filing for the potential approval of balstilimab as treatment of recurrent/metastatic cervical cancer, announced Agenus Inc, in a press release.¹

Late responses among patients in a phase 2 trial of balstilimab has caused the FDA to delay the completion of the BLA filing is planned for the first half of 2021. Agenus, Inc is also working with the FDA to solidify the diagnostic requirements for PD-L1 testing.

Plans for submission of the rolling BLA were announced in September 2020 after positive data were presented on the drug alone and in combination with zalifrelimab during the European Society for Medical Oncology (ESMO) Virtual Annual Meeting. The phase 2 study of balstilimab plus zalifrelimab showed encouraging objective response rates (ORRs) regardless of the PD-L1 status of patients and also showed a tolerable safety profile.

There was a total of 161 patients enrolled in the single-agent trial (NCT03104699), and 160 were a part of the modified intention-to-treat (ITT) population. Of those included, 138 patients had previously received 1 or more prior line of chemotherapy. The median age of the population was 53 years. Forty-seven percent of the patients had an ECOG performance status of 0, and 62% of patients had a CPS of 1% or higher. Squamous cell histology was seen in 63%of patients, and 37% had an adenocarcinoma or adenosquamous histology. All patients were treated with balstilimab at 3 mg/kg every 2 weeks and zalifrelimab at a dose of 1 mg/kg every 6 weeks.²

The combination trial (NCT03495882) included 155 patients in the safety population. One hundred-nineteen patients had received 1 or more lines of chemotherapy. The modified ITT population included 143 patients with measurable disease. Patients had a median age of 50 years. Fifty-seven percent of patients had an ECOG performance status of 0, and 55% of patients had a CPS of 1% or higher. In terms of histology, 70% of patients had squamous disease and 30% had adenocarcinoma/adenosquamous histology.

Single-agent balstilimab led to an ORR of 14% ORR in the ITT population, which included 3 complete responses (CRs) and 20 partial responses (PRs). The combination of balstilimab and zalifrelimab achieved a higher ORR of 22%, which included 8 CRs and 23 PRs. The median duration of response (DOR) observed was 15.4 months (1.1+ to 15.4) with single-agent balstilimab and was not reached (1.3+ to 16.6+) when zalifrelimab was added to balstilimab.

Single-agent balstilimab was well-tolerated in patients. No new safety signals were observed. Balstilimab in combination with zalifrelimab led to both immune-related adverse events and gastrointestinal toxicities. In addition, all-grade endocrine disorders were observed with both single-agent balstilimab and the combination which occurred in 20.6% vs 9.3% of patients, respectively.

Following the request from the FDA, patients additional follow-up will ensue for the 2 patients who experienced durable disease stabilization and later had confirmed responses on long-term balstilimab therapy.

_References:

_{1. Completion of balstilimab BLA filing extended to 1h2021.News release. Agenus, Inc. December 4, 2020. Accessed December 4, 2020. https://bit.ly/2VDlc26}

_{2. O’Malley DM, Oaknin A, Monk B, et al. 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. Presented at: 2020 ESMO Congress; September 19-21, 2020; Virtual. Abstract LBA34.}