FDA Grants Priority Review to Balstilimab for Recurrent or Metastatic Cervical Cancer

The FDA has granted priority review to the biologics license application (BLA) for balstilimab for use in the treatment of patients with recurrent or metastatic cervical cancer who experienced disease progression on, or after, chemotherapy.¹

The application is supported by findings from a phase 2 trial (NCT03894215), which indicated that the agent has differentiated features from other anti–PD-1 antibodies.² Moreover, the submission was based on an update to findings presented during the 2020 ESMO Virtual Congress that were published in Oncogene and showed that balstilimab elicited a response rate of 20% in patients whose tumors have PD-L1 positivity, and 15% in all tumors.³ The median duration of response (DOR) achieved with the immunotherapy was 15.4 months.

The regulatory agency is expected to decide on the application by December 16, 2021, under the Prescription Drug User Fee Act.

“We expect that the potential approval of balstilimab will enable us to better pursue our oncology combination strategy of our own extensive pipeline of agents as well as for exciting and future partner products,” Steven O’Day, MD, chief medical officer at Agenus, stated in a prior press release. “In particular, we hope to use this potential approval to allow us to rapidly proceed with our anti–CTLA-4 combination strategy, which we believe can add significantly to the benefit provided by our anti–PD-1 agent.”

Preliminary data from 2 independent, single-arm phase 2 trials (NCT03104699, NCT03495882) were presented during the 2020 ESMO Virtual Congress.⁴ To be eligible for enrollment, patients needed to have histologically confirmed squamous cell cancer, adenosquamous cancer, and adenocarcinoma of the cervix that relapsed following platinum-based therapy. Patients also needed to have measurable disease and an ECOG performance status of 0 or 1.

In the monotherapy trial, balstilimab was given at a dose of 3 mg/kg every 2 weeks to a total of 161 patients. In the combination trial, balstilimab was given at a dose of 3 mg/kg every 2 weeks in combination with zalifrelimab (AGEN1884), which was administered at a dose of 1 mg/kg every 6 weeks. Treatment was administered for up to 24 months.

The primary end point of the trials was ORR per independent review committee and RECIST v1.1 criteria, while key secondary end points included DOR, progression-free survival, and overall survival.

Results showed that in the modified intent-to-treat (mITT) population (n = 160), single-agent balstilimab elicited an objective response rate of 14% (95% CI, 10%-21%), with a complete response (CR) rate of 2% and a partial response (PR) rate of 12%. Among those with PD-L1 positivity (n = 99), the ORR was 19% (95% CI, 13%-28%). Among the 42 patients whose tumors did not express PD-L1, the ORR achieved with balstilimab was 10% (95% CI, 4%-22%).

In a subgroup of patients who had received at least 1 prior chemotherapy (n = 138), the ORR achieved with the agent was 13% (95% CI, 8%-20%), with a CR and PR rate of 2% and 11%, respectively. Among those with PD-L1 positivity (n = 84) and negativity (n = 37), these rates were 18% (95% CI, 11%-27%) and 8% (95% CI, 3%-21%), respectively.

When paired with zalifrelimab in the mITT population (n = 143), the regimen induced an ORR of 22% (95% CI, 16%-29%); the CR rate in this group was 6%, and the PR rate is 16%. These rates were 27% (95% CI, 19%-37%) and 11% (95% CI, 4%-25%), respectively, in those whose tumors were PD-L1 positive (n = 79) or negative (n = 36).

In the subgroup of patients who had previously received at least 1 line of chemotherapy (n = 119), the doublet elicited an ORR of 20% (95% CI, 14%-28%), with a CR rate of 5% and a PR rate of 15%. Among those with PD-L1 positivity (n = 61), the ORR with the combination was 26% (95% CI, 17%-38%). In those who were negative for PD-L1 (n = 33), the ORR achieved with the doublet was 9% (95% CI, 3%-24%).

Single-agent balstilimab and balstilimab plus zalifrelimab were found to have tolerable safety profiles. Adverse effects that were reported with both regimens included gastrointestinal toxicities, general disorder and administration site conditions, blood and lymphatic systemic disorders, musculoskeletal and connective tissue disorders, metabolism and nutrition, and laboratory abnormalities, among others.

References

1. Agenus announces US FDA acceptance and priority review of balstilimab biologics license application for the treatment of recurrent or metastatic cervical cancer. News release. Agenus Inc. June 17, 2021. Accessed June 17, 2021. https://bit.ly/3gGHfPx
2. Agenus submits balstilimab biologics license application to the US FDA for patients with recurrent or metastatic cervical cancer. News release. Agenus Inc. April 19, 2021. Accessed June 17, 2021. https://bit.ly/2P103PA
3. Grossman JE, Vasudevan D, Joyce CE, et al. Is PD-L1 a consistent biomarker for anti–PD-1 therapy? The model of balstilimab in a virally-driven tumor. Oncogene. 2021;40(8):1393-1395. doi:10.1038/s41388-020-01611-6
4. O’Malley DM, Oaknin A, Monk BJ, et al. LBA34 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 trial. Ann Oncol. 2020;31(4):S1164-S1165. doi:10.1016/j.annonc.2020.08.2264