FDA Grants Fast Track Designation to Balstilimab/Zalifrelimab Combination for Cervical Cancer

The FDA granted fast track designation to balstilimab and zalifrelimab based on comprehensive data found to support their potential as a combination therapy.

The FDA granted fast track designation for investigation of balstilimab in combination with zalifrelimab for the treatment of patients with relapsed or refractory metastatic cervical cancer, according to Agenus, the agent’s developer.1

The designation was based on comprehensive data that supported the potential for balstilimab and zalifrelimab. 

“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,” said Jennifer Buell, PhD, president and COO of 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.”

Following this regulatory action, the company anticipates filing 2 biologics license applications (BLAs) this year for accelerated approval of the combination of balstilimab and zalifrelimab and balstilimab monotherapy in metastatic cervical cancer. 

Updated data reported by Agenus from a pre-planned interim analysis revealed robust and durable activity of balstilimab and zalifrelimab in patients with relapsed or refractory metastatic cervical cancer. The data demonstrated 26.5% objective response rates (ORR) which are durable in an all-comer, non-biomarker selected population of patients with refractory cervical cancer who have failed prior platinum chemotherapy with or without bevacizumab. Four patients had a complete response (CR), 5 had a partial response (PR), and 8 were found to have stable disease (SD), though the median has not yet been reached.

In February, early data from the pre-planned interim analysis of balstilimab and zalifrelimab were announced, as well as data from an analysis of balstilimab monotherapy.2 For 34 evaluable patients, researchers observed an ORR of 20.6% in the combination arm, which included an 8.8% CR rate. Of the 44 patients evaluable in the balstilimab monotherapy analysis, the ORR was 11.4%.

Moreover, clinical activity in both studies has been comparable to other agents in their classes. Further, the combination therapy and monotherapy were found to be well-tolerated among patients with no new safety signals found. 

Balstilimab is a PD-1 inhibitor and zalifrelimab is a CTLA-4 inhibitor.3 Balstilimab is under ongoing evaluation in combination with investigational PD-1 inhibitor AGEN1181 in a phase I dose-escalation study including patients with advanced solid tumors, which began in April 2019.


1. Agenus Receives Fast Track Designation for Balstilimab & Zalifrelimab in Advanced Cervical Cancer [news release]. Lexington, Massachusetts. Published March 12, 2020. investor.agenusbio.com/2020-03-12-Agenus-Receives-Fast-Track-Designation-for-Balstilimab-Zalifrelimab-in-Advanced-Cervical-Cancer. Accessed March 13, 2020. 

2. Agenus Announces Positive Interim Data from Balstilimab and Zalifrelimab Clinical Trials in Second-Line Cervical Cancer [news release]. Lexington, Massachusetts. Published February 20, 2020. investor.agenusbio.com/2020-02-20-Agenus-Announces-Positive-Interim-Data-from-Balstilimab-and-Zalifrelimab-Clinical-Trials-in-Second-Line-Cervical-Cancer. Accessed March 13, 2020.

3. Agenus Commences Combination Trial of its Next-Gen CTLA-4 with its PD-1 Antibody [news release]. Lexington, Massachusetts. Published December 19, 2019. investor.agenusbio.com/2019-12-19-Agenus-Commences-Combination-Trial-of-its-Next-Gen-CTLA-4-with-its-PD-1-Antibody. Accessed March 13, 2020.