In a phase II trial reported in the Journal of Clinical Oncology, David M. O’Malley, MD, and colleagues found that the PD-1 inhibitor balstilimab and the CTLA-4 inhibitor zalifrelimab—both investigational agents—produced durable responses as second-line treatment for patients with recurrent or metastatic cervical cancer who relapsed after prior platinum-based therapy.

David M. O’Malley, MD

Study Details

In the study, 155 women enrolled from sites in the United States, Europe, South America, and Australia between August 2018 and May 2020 received balstilimab at 3 mg/kg once every 2 weeks and zalifrelimab at 1 mg/kg once every 6 weeks for up to 24 months.

The primary endpoint was objective response rate on independent central review. A total of 125 patients with measurable disease at baseline constituted the efficacy evaluable population.

Responses

At data cutoff (April 2021), median follow-up was 21 months (range = 11.8–32.1+ months). An objective response was observed in 32 (25.6%, 95% confidence interval [CI] = 18.8%–33.9%) of 125 evaluable patients, including complete response in 10 (8%). Median duration of response was not reached, with responses ongoing at 6, 9, and 12 months in 86.5%, 75.5%, and 64.2% of responders, respectively. The overall disease control rate was 52% (95% CI = 43.3%–60.6%).

Among patients with known PD-L1 status, objective response rates were 32.8% among 86 PD-L1–positive patients (combined positive score ≥ 1%) and 9.1% among 33 PD-L1–negative patients. Objective response rates were 32.6% among 89 patients with squamous cell carcinoma and 8.85% among 34 with adenocarcinoma.

At data cutoff, median progression-free survival was 2.7 months (95% CI = 1.5–3.7 months), with a 12-month rate of 21.3%. Median overall survival was 12.8 months (95% CI = 8.8–17.6 months) with 6- and 12-month rates of 69.2% and 53.3%.

Adverse Events

Among all 155 patients, treatment-related grade ≥ 3 adverse events occurred in 20.0%, the most commonly reported being increased alanine aminotransferase (2.6%) and diarrhea (1.9%). Serious treatment-related adverse events occurred in 10.3% of patients, most commonly enterocolitis (n = 3).

Treatment-related adverse events led to discontinuation of treatment in 7.7%. Treatment-related death occurred in three patients, due to pneumonitis, nephritis, and diabetes mellitus, respectively. Immune-mediated adverse events occurred in 44.5% of patients, most commonly, hypothyroidism (14.2%), hyperthyroidism (7.1%), and diarrhea (7.1%).

The investigators concluded, “Promising and durable clinical activity, with favorable tolerability, was seen in this largest trial to date evaluating dual PD-1/ CTLA-4 blockade in patients with recurrent and/or metastatic cervical cancer. Further investigation of the balstilimab and zalifrelimab combination in this setting is continuing.”

David M. O’Malley, MD, of The Ohio State University and James Comprehensive Cancer Center, Columbus, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Agenus Inc. For full disclosures of the study authors, visit ascopubs.org.