Dual checkpoint blockade shows promising activity in advanced cervical cancer
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Balstilimab plus zalifrelimab demonstrated promising and durable activity among women with recurrent and/or metastatic cervical cancer who relapsed after platinum-based therapy, according to a phase 2 study in Journal of Clinical Oncology.
The combination of checkpoint inhibitors also showed favorable tolerability, researchers wrote.
“Thanks to screening, most cervical cancers are detected in early or precancerous stages that are very treatable. For women with an advanced or recurrent cancer, however, there are still limited medical therapies that provide durable cancer control,” David M. O’Malley, MD, professor in the department of obstetrics and gynecology and director of the division of gynecologic oncology at The Ohio State University Comprehensive Cancer Center, said in a press release. “[These data suggest] the combination of balstilimab [AGEN2034, Agenus] and zalifrelimab [AGEN1884, Agenus] is an effective and durable new option for treating advanced or recurrent cervical cancers — particularly in patients whose tumors express PD-L1.”
Background and methodology
The open-label, single-arm, global trial included 155 women (median age, 50 years; range, 24-76; 95.5% white) enrolled between Aug. 27, 2018, and May 7, 2020. The efficacy-evaluable population consisted of 125 of these women who had measurable disease at baseline and one prior line of platinum-based therapy in the advanced setting.
The women received IV doses of 3 mg/kg balstilimab, an anti-PD-1 agent, every 2 weeks plus 1 mg/kg zalifrelimab, an anti-CTLA-4 antibody, every 6 weeks.
Treatment continued for up to 24 months or until disease progression, development of unacceptable toxicity, or an investigator or patient’s decision to withdraw, with median follow-up of 21 months.
Objective response rate, assessed by independent central review, served as the primary efficacy endpoint.
Key findings
Results showed a confirmed ORR of 25.6% (95% CI, 18.8-33.9), including 10 complete responders and 22 partial responders, with median duration of response not reached (86.5% estimated rate of duration at 6 months, 75.5% at 9 months and 64.2% at 12 months). Further analysis revealed an overall disease control rate of 52% (95% CI,43.3-60.6).
Researchers reported an ORR of 32.8% in patients with PD-L1-positive tumors, 9.1% in those with PD-L1-negative tumors, and 32.6% in those with squamous cell carcinoma.
The most common immune-mediated adverse events included hypothyroidism (14.2%) and hyperthyroidism (7.1%).
Implications
O’Malley and colleagues called the results of the trial “promising.”
“The high proportion of complete responders and activity irrespective of tumor PD-L1 status or histology were particularly promising outcomes that confirm the feasibility of dual targeted immunotherapy for this disease,” they wrote. “Given the lack of effective therapies and poor prognosis for patients in this setting, the findings suggest that this novel regimen may provide meaningful clinical benefit in this difficult-to-treat population and further evaluation of the combination is warranted.”
References:
O'Malley DM, et al. J Clin Oncol. 2022;doi:10.1200/JCO.21.02067.
Targeted two-drug therapy effective to treat advanced cervical cancer. https://cancer.osu.edu/news/targeted-two-drug-therapy-effective-to-treat-advanced-cervical-cancer. Published Jan. 5, 2022. Accessed Jan. 12, 2022.
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