A pair of immune checkpoint inhibitors — balstilimab and zalifrelimab — produced durable responses in patients with recurrent and/or metastatic cervical cancer, according to phase 2 results published in the Journal of Clinical Oncology.

“To our knowledge, this is the largest study report assessing dual targeting of PD-1 and CTLA-4 as a therapeutic modality in this disease setting to date,” the researchers wrote.

The phase 2 trial (ClinicalTrials.gov identifier: NCT03495882) was designed to evaluate the efficacy and safety of balstilimab plus zalifrelimab in patients with recurrent and/or metastatic cervical cancer who relapsed after prior platinum-based therapy.

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The study enrolled 155 patients with squamous cell carcinoma (70.3%), adenocarcinoma (27.1%), and adenosquamous carcinoma (2.6%). The patients’ median age was 50 years (range, 24-76 years).

The 125 patients who had relapsed after platinum-based treatment comprised the evaluable population, and 12 patients were still on study treatment at the time of analysis.

The objective response rate (ORR) was 25.6%, with a complete response rate of 8% and a partial response rate of 17.6%. At a median follow-up of 21 months, the median duration of response was not reached. The median time to response was 2.7 months, and the disease control rate was 52%.

An exploratory analysis showed an ORR of 32.8% in the 67 patients with PD-L1-positive disease and an ORR of 9.1% in the 33 patients with PD-L1-negative disease.

When patients were analyzed by histologic subtype, the greatest benefit was seen in those with squamous cell carcinoma, with an ORR of 32.6%. Patients with cervical adenocarcinomas had an ORR of 8.8%. There were no responses in the adenosquamous carcinoma group.

At the data cutoff, the median progression-free survival (PFS) was 2.7 months, and the 12-month PFS rate was 21.3%. The median overall survival (OS) was 12.8 months. The 6-month OS rate was 69.2%, and the 12-month OS rate was 53.3%.

The most common any-grade treatment-related adverse events (TRAEs) were hypothyroidism (16.8%), diarrhea (14.2%), fatigue (11.6%), and nausea (9.0%).

Grade 3 or higher TRAEs occurred in 20% of patients. The most common were ALT increase (2.6%) and diarrhea (1.9%). TRAEs leading to dose interruptions occurred in 12.3% of patients, and TRAEs leading to treatment discontinuation occurred in 7.7%.

There were 3 treatment-related deaths reported. The causes of death were pneumonitis, immune-mediated nephritis, and diabetes mellitus.

“This novel combination regimen provides meaningful clinical benefit for a patient population with significant unmet medical need and lack of effective therapies,” the researchers wrote. “On the basis of these findings, further evaluation of balstilimab plus zalifrelimab as second-line treatment in this disease setting is warranted.”

Disclosures: This research was supported by Agenus Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


O’Malley DM, Neffa M, Monk BJ, et al. Dual PD-1 and CTLA-4 checkpoint blockade using balstilimab and zalifrelimab combination as second-line treatment for advanced cervical cancer: An open-label phase II study. J Clin Oncol. Published online December 21, 2021. doi:10.1200/JCO.21.02067