BLA Submission for Balstilimab in Recurrent/Metastatic Cervical Cancer Delayed

The completion of the biologics license application (BLA) for balstilimab in the treatment of patients with recurrent or metastatic cervical cancer has been delayed to the first half of 2021, according to an announcement from Agenus Inc.¹

The decision follows feedback from the FDA to follow all patients for a median of 12 months and responders to treatment for a minimum of 6 months, as two newly-identified late responses have been identified in the trial examining the agent’s use.

Specifically, the additional follow-up is needed to present data on 2 patients who went from having durable disease stabilization to confirmed responses on long-term treatment with balstilimab.

The clinical-stage immune-oncology company is also working with the regulatory agency to refine diagnostic requirements for PD-L1 testing.

The rolling submission for balstilimab in this indication was announced in October 2020 based on findings from an ongoing phase 2 trial (NCT03894215), which demonstrated that the monotherapy elicited encouraging responses in patients with advanced cervical cancer.

Updated data presented during the 2020 ESMO Virtual Congress showed that the best overall response with single-agent balstilimab was 14% (n = 23; 95% CI, 10-21) and 13% (n = 18; 95% CI, 8-20) in the modified intent-to-treat population (mITT; n = 160) and in those who previously received 1 or more lines of chemotherapy (n = 138), respectively.² The duration of response (DOR) in both groups was 15.4 months.

In the mITT population, 3 patients achieved a complete response (CR) and 20 patients experienced a partial response. In those with PD-L1 positivity, the ORR was 19% (95% CI, 13-28) versus 10% (95% CI, 4-22) in those who did not express PD-L1. In the subgroup of patients who received 1 or more lines of previous chemotherapy, 3 patients had a CR and 15 experienced a PR. In those with PD-L1 positivity, the ORR was 18% (95% CI, 11-27) versus 8% (95% CI, 3-21) in those who did not express PD-L1.

The multicentric international clinical trial enrolled a total of 161 patients. To be eligible for enrollment, patients had to have histologically confirmed squamous cell carcinoma, adenosquamous carcinoma, adenocarcinoma of the cervix and have relapsed after platinum-based treatment. Patients had to have measurable disease and an ECOG performance status of 0 or 1.

Patients received the agent at a dose of 3 mg/kg every 3 weeks for up to 24 months. For the follow-up portion of the trial, imaging will be done every 6 weeks for the duration of 2 years. The primary end point of the trial was overall response rate (ORR) via independent review committee (IRC) by RECIST v1.1 criteria, while key secondary end points included DOR, progression-free survival, and overall survival.

The median age of participants in the safety population (n = 161) and the subset of patients who previously received 1 or more previous chemotherapy (n = 138) was 53 years. Forty-seven percent of patients had an ECOG performance status of 0, while 52% had a status of 1. Sixty-two percent (n = 99) of patients in the safety population had a PD-L1 combined positive score of 1% or greater, while 26% (n = 42) had a score of less than 1%; in the chemotherapy subset, these rates were 61% (n = 84) and 27% (n = 37), respectively. The majority of patients in both populations had squamous disease.

All participants had previously received platinum systemic therapy. Twenty-nine percent (n = 46) of those in the safety population had previously received bevacizumab (Avastin) as systemic therapy versus 33% (n = 46) of those in the chemotherapy subset.

With regard to safety, the most commonly reported adverse effect (AE) was a general disorder an administration site condition, which occurred in 33.5% (n = 54) of patients who received balstilimab; 1 patient experienced this at grade 3 or higher. Additionally, all-grade gastrointestinal toxicity was observed in 25.5% (n = 41) of patients, while 14.3% (n = 23) of patients had all-grade blood and lymphatic system disorder.

Looking specifically at immune-related AEs, 5.6% (n = 9) of patients experienced gastrointestinal disorders, 5.6% (n = 9) of patients had laboratory abnormalities, and 5.0% (n = 8) had endocrine disorders. Immune-treated AEs associated with treatment included gastrointestinal disorders (3.1%; n = 5), laboratory abnormalities (1.2%; n = 2), and skin and soft tissue disorders (0.6%; n = 1).

In April 2020, the FDA granted balstilimab a fast track designation for the treatment of patients with cervical cancer. In the month prior, March 2020, the FDA granted a fast track designation to balstilimab in combination with zalifrelimab for patients with relapsed or refractory cervical cancer.

Updated data with this combination were also presented during the 2020 ESMO Virtual Congress and showed that the regimen elicited an ORR of 22% (95% CI, 16-29) in the mITT population (n = 143) and 20% (95% CI, 14-28) in those who previously received 1 or more lines of chemotherapy (n = 119).

References

1. Completion of balstilimab BLA filing extended to 1H2021. News release. Agenus Inc. December 3, 2020. Accessed December 4, 2020. https://bit.ly/39Faalb.
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