FDA Grants Balstilimab/Zalifrelimab Dual Immunotherapy Fast Track Designation in Cervical Cancer

Jennifer Buell, PhD

The FDA has granted a Fast Track designation to the combination of the PD-1 inhibitor balstilimab and the CTLA-inhibitor zalifrelimab for the treatment of patients with relapsed or refractory metastatic cervical cancer.¹

An early study evaluating the combination showed durable responses in an all-comer, nonbiomarker selected population of patients with refractory cervical cancer who progressed following prior platinum-based chemotherapy with or without bevacizumab (Avastin). The latest data from the study showed that the combination induced an objective response rate (ORR) of 26.5%, including 4 complete responses (CRs) and 5 partial responses (PRs). Eight patients had a best response of stable disease.

"We are pleased that balstilimab and zalifrelimab have been granted Fast Track designation by FDA in recognition of the high unmet medical need in second line cervical cancer. The Fast Track designation confers important benefits, including the potential eligibility for a Priority Review," Jennifer Buell, PhD, president and COO, Agenus, said in a press release. "We are excited about the prospect of making these novel agents available to women who suffer from metastatic cervical cancer. We look forward to continuing to work with FDA as we advance new treatment options for patients with cancer."

Data initially reported from the study of the 2 drugs showed that combination induced an ORR of 20.6% in 34 evaluable patients, including a CR rate of 8.8% in the second-line setting.² The combination was considered by the investigators to be well tolerated.

Agenus reported in the press release that the company plans to file applications to the FDA this year for both the balstilimab/zalifrelimab combination and single-agent balstilimab for the treatment of patients with metastatic cervical cancer.

Overall, researchers in the cervical cancer field hope that immunotherapy offers a gateway to improve on the results chemotherapy offers patients with this disease. Investigators are all hoping to build on the initial success with the PD-1 inhibitor pembrolizumab (Keytruda).

In June 2018, the FDA granted pembrolizumab an accelerated approval for the treatment of patients with advanced, PD-L1—positive cervical cancer with disease progression on or after chemotherapy. The approval defined PD-L1 positivity as a combined positive score (CPS) of ≥1 as measured by an FDA-approved test.

The FDA based its decision on data from 98 patients with recurrent or metastatic cervical cancer enrolled in a single cohort in the phase II KEYNOTE-158 trial.³ The global, open-label, nonrandomized, multicohort, multicenter study evaluated pembrolizumab in patients with multiple types of advanced solid tumors who progressed on standard of care therapy.

Results showed that the ORR was 12.2% (95% CI, 6.5-20.4) with 3 CRs and 9 PRs. Overall, the median progression-free survival was 2.1 months (95% CI, 2.0-2.1) and the median overall survival (OS) was 9.4 months (95% CI, 7.7-13.1). All 12 responses were in patients with PD-L1—positive tumors, for an ORR of 14.6% (95% CI, 7.8-24.2). The median OS was 11.1 months (95% CI, 9.1-14.1) in the PD-L1–positive population.

The hope to build on this success, R. Wendel Naumann, MD, recently told an audience at the 2020 SGO Winter Meeting, is that cervical cancer is a virally induced tumor that should be highly angiogenic. Virus-induced cancers generally make good targets for immunotherapy because viral proteins are strong immune stimulants, Naumann, professor and director of minimally invasive surgery in gynecologic oncology with Levine Cancer Institute, Carolinas Medical Center, Atrium Health, explained to the attendees.

References

1. Agenus Receives Fast Track Designation for Balstilimab & Zalifrelimab in Advanced Cervical Cancer. Accessed March 12, 2020. https://investor.agenusbio.com/2020-03-12-Agenus-Receives-Fast-Track-Designation-for-Balstilimab-Zalifrelimab-in-Advanced-Cervical-Cancer. Published March 12, 2020.
2. Agenus Announces Positive Interim Data from Balstilimab and Zalifrelimab Clinical Trials in Second-Line Cervical Cancer. Published online February 20, 2020. https://investor.agenusbio.com/2020-02-20-Agenus-Announces-Positive-Interim-Data-from-Balstilimab-and-Zalifrelimab-Clinical-Trials-in-Second-Line-Cervical-Cancer. Accessed March 12, 2020.
3. Chung HC, Ros W, Delord JP, et al. Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol. 2019;37(17):1470-1478. doi: 10.1200/JCO.18.01265.