FDA Approval Sought for Balstilimab for Recurrent or Metastatic Cervical Cancer


A biologics license application has been submitted to the FDA seeking the accelerated approval of balstilimab for use in the treatment of patients with recurrent or metastatic cervical cancer with disease progression on, or following, chemotherapy.

Jennifer Buell, PhD

Jennifer Buell, PhD

A biologics license application (BLA) has been submitted to the FDA seeking the accelerated approval of balstilimab for use in the treatment of patients with recurrent or metastatic cervical cancer with disease progression on, or following, chemotherapy.1

The application was based on data from a pivotal phase 2 trial (NCT03894215), which showed that the agent elicited encouraging responses in patients with advanced cervical cancer.

Data presented during the 2020 ESMO Virtual Congress indicated a best overall response rate (ORR) of 14% with balstilimab monotherapy (n = 23; 95% CI, 10%-21%) in the modified intent-to-treat (mITT) population (n = 160) and 13.0% (n = 18; 95% CI, 8%-20%) in a subset of patients who receive 1 or more prior lines of chemotherapy (n = 138). The duration of response (DOR) with the agent in both groups was 15.4 months.

In the mITT population, 3 patients experienced a complete response (CR), and 20 patients achieved a partial response (PR). Among the patients with PD-L1 positivity, the ORR was 19.0% (95% CI, 13%-28%) compared with 10.0% (95% CI, 4%-22%) in those without PD-L1 expression. In the subset of patients who had previously received 1 or more lines of chemotherapy, 3 achieved a CR and 15 had a PR. Here, the ORR was 18.0% (95% CI, 11%-27%) in those with PD-L1–positive disease and 8.0% (95% CI, 3%-21%) in those without PD-L1 expression.

“Women with recurrent or metastatic cervical cancer have a very poor prognosis and limited treatment options,” Jennifer Buell, PhD, president and chief operating officer at Agenus, stated in a press release. “This submission also marks a significant step in our transition to a commercial company and the advancement of our oncology combination strategy.”

In December 2020, the completion of the BLA for balstilimab in this indication was delayed for the first half of 2021 after the FDA asked that all patients be followed for a median of 12 months and responders to treatment to be followed for a minimum of 6 months because 2 newly-identified late responses were identified in the trial. Moreover, additional follow-up was needed to present findings on 2 patients who went from having durable disease stabilization to confirmed responses on long-term treatment with the agent.

A total of 161 patients were enrolled to the multicentric international trial. Patients needed to have histologically confirmed squamous cell carcinoma, adenosquamous carcinoma, adenocarcinoma of the cervix and have relapsed following platinum-based treatment, in order to enroll. They also needed to have measurable disease and an ECOG performance status of 0 to 1.

Study participants were given balstilimab at 3 mg/kg every 3 weeks for up to 24 months. In the follow-up portion of the trial, investigators will do imaging every 6 weeks for 2 years. The primary objective of the trial is ORR per independent review committee and RECIST v1.1 criteria. Important secondary end points comprised DOR, progression-free survival, and overall survival.

The median age was 53 years in the safety population (n = 161) and the subset of patients who received 1 or more prior lines of chemotherapy (n = 138). Moreover, 47% of patients had an ECOG performance status of 0. In the safety population, 62% of patients had a PD-L1 combined positive score of 1% or greater and 26% had a score of less than 1; in the chemotherapy subgroup, these rates were 61% and 27%, respectively. Most patients in both populations had squamous disease.

All patients on the trial had received prior platinum systemic therapy. Additionally, in the safety and chemotherapy populations, 29% and 33% of patients, respectively, had prior bevacizumab (Avastin).

The most frequently reported toxicity was general disorder at an administration site condition; this was observed in 33.5% of patients who were given balstilimab. One of these patients experienced this effect at a severity that was grade 3 or higher. All-grade gastrointestinal toxicity was reported in 25.5% of patients and 14.3% experienced all-grade blood and lymphatic system disorder with the agent.

Moreover, 5.6% of patients were observed to have gastrointestinal disorders, 5.6% had laboratory abnormalities, and 5.0% experienced endocrine disorders. Immune-related adverse effects that were determined to be associated with treatment included gastrointestinal disorders (3.1%), laboratory abnormalities (1.2%), as well as skin and soft tissue disorders (0.6%).

“We expect that the potential approval of balstilimab will enable us to better pursue our oncology combination strategy for our own extensive pipeline of agents as well as for existing and future partner products,” Steven O’Day, MD, chief medical officer at Agenus, added in the 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.”

Previously, in April 2020, the FDA granted balstilimab a fast track designation for the treatment of patients with cervical cancer. In March 2020, the agent was granted fast track designation for use in combination with zalifrelimab in patients with relapsed or refractory cervical cancer.


  1. Agenus submits balstilimab biologics license application to the US FDA for patietns with recurrent or metastatic cervical cancer. News release. Agenus Inc. April 19, 2021. Accessed April 19, 2021. https://bit.ly/2P103PA
  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. Ann Oncol. 2020;31(suppl 4):S1164-S1165. doi:10.1016/j.annonc.2020.08.2264
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