Balstilimab for patients with metastatic cervical cancer


Results of a phase 2 study demonstrate that the anti-programmed death-1 (PD-1) antibody balstilimab from Agenus Inc. provides meaningful and durable clinical activity in patients with previously treated, recurrent/metastatic cervical cancer.

The study in the journal Gynecologic Oncology also found that the safety profile of the therapy is comparable to other PD-1 inhibitors that have been reported or approved.

David M. O’Malley, MD

David M. O’Malley, MD

Balstilimab is an investigational, fully human monoclonal antibody that binds with high affinity to PD-1 and is designed to prevent the interaction between this receptor and its ligands PD-L1 and PD-L2, according to principal investigator David M. O’Malley, MD, professor and director of gynecologic oncology at The Ohio State University and the James Cancer Center in Columbus, Ohio. “By functioning as a PD-1 antagonist, balstilimab enhances T-cell receptor (TCR) signaling and T-cell responsiveness under conditions of TCR stimulation,” he said.

The study comprised 161 women, 18 years or older (media age 53), with recurrent and/or metastatic cervical cancer and who had relapsed after a prior platinum-based treatment regimen for advanced disease. All enrollees were treated with balstilimab intravenously at 3 mg/kg once every 2 weeks, for up to 24 months.

The primary endpoint was the objective response rate (ORR), as assessed by an independent review committee.

“Of the entire cohort, 15% had an ORR and 4% had a complete response (CR) to balstilimab,” O’Malley told Contemporary OB/GYN®.

The median duration of response was 15.4 months, across the entire breadth of cervical cancer patients.

In patients with PD-L1-positive tumors the ORR was 20%. Patients with PD-L1-negative tumors also responded to balstilimab, for which the ORR was 7.9%.

In addition, responses were not restricted to tumors of squamous cell histology. For instance, an ORR of 12.5% was seen in patients with cervical adenocarcinoma.

“Overall, the duration of response was impressive, with over 50% of responses sustained at 12 months among those patients who had that length of follow-up,” O’Malley said.

The 2 most common grade 3 or higher treatment-related adverse events were immune-mediated enterocolitis (3.1%) and diarrhea (1.9%).

“The greatest surprise was the responses seen across all groups of patients with recurrent, progressive cervical cancer, including those who were PDL-1 negative, were adenocarcinoma histology or were pretreated with bevacizumab, as well as those previously described as having PDL-1+ and squamous histology,” O’Malley said.

In addition to a favorable tolerability profile, “balstilimab represents an attractive candidate for use as a backbone in combination-based therapeutic approaches,” O’Malley said.

Nonetheless, because there are known toxicities in patients treated with PD-1 intravenously, “it is important to have a high clinical suspicion,” O’Malley said. “Timely identification and treatment are key.”

Study results indicate that balstilimab might be a differentiated anti-PD-1 antibody as compared to currently approved PD-1 inhibitors. For instance, pembrolizumab in the same setting has been shown to have an ORR of 14.6% in the PD-L1 positive population, but no observed responses in the PD-L1 negative population.

An ongoing phase 2 study of balstilimab alone or in combination with the novel cytotoxic T-lymphocyte-associated protein 4 inhibitor zalifrelimab (NCT03495882) is assessing the feasibility of dual immune checkpoint blockade for further improving outcomes in this patient population.


O’Malley is a consultant and advisor to Agenus.


O’Malley DM, Oaknin A, Monk BJ, et al. Phase II study of the safety and efficacy of the anti-PD-1 antibody balstilimab in patients with recurrent and/or metastatic cervical cancer. Gynecol. Oncol. Published online August 25, 2021. doi:org/10.1016/j.ygyno.2021.08.018

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