The Lynx Group

Balstilimab Shows Promise in the Treatment of Advanced Cervical Cancer

October 2021, Vol 12, No 5

According to results from a recent study, balstilimab, an investigational PD-1 inhibitor, demonstrated meaningful and durable clinical activity in patients with recurrent or metastatic cervical cancer. These findings were presented by Cailin E. Joyce, MD, Director, Applied Technology, Agenus, Boston, MA, during the American Society of Clinical Oncology 2021 virtual annual meeting

In contrast to other inhibitors in the same class, responses to balstilimab occurred irrespective of tumor PD-L1 status or histology, indicating a potential opportunity to extend the therapeutic reach of immune checkpoint blockade to a greater proportion of patients.

Study Details

Balstilimab, a novel, fully human monoclonal immunoglobulin G4 (IgG4) antibody, was studied as monotherapy in a phase 2 clinical trial of 140 patients with recurrent or metastatic cervical cancer that had relapsed following platinum-based chemotherapy for advanced disease. The primary end point of the trial was overall response rate. Secondary end points included duration of response, disease control rate, progression-free survival, and overall survival.

Results showed that overall, 17.6% of patients with metastatic cervical cancer who received balstilimab responded to treatment, regardless of their PD-1/PD-L1 status. The average length of response was 15.4 months, a significant extension of survival for this patient population.

In patients with squamous-cell carcinoma (the most common type of cervical cancer), the response rate was 17.6%, which increased to 21.0% in those who had PD-L1 expression. In patients with adenocarcinoma (the second most common type of cervical cancer), the response rate was 12.5%, which increased to 20.0% in those with adenocarcinoma associated with PD-L1 expression.

Median duration of response was 15.4 months in patients with squamous-cell carcinoma and 8.5 months in patients with adenocarcinoma. In patients with PD-L1 and squamous-cell carcinoma, the average duration of response was not reached, and was 7.1 months in those with adenocarcinoma.

“In the phase 2 study, balstilimab exhibited higher overall response rates and duration of responses than those reported for other PD-1 antibodies,” said Dr Joyce. “Notably, balstilimab exhibited durable responses even in patients with poorest prognosis due to PD-L1–negative status or adenocarcinoma histology.”

Results Support Earlier Findings

These results support findings from an earlier investigation using a proprietary platform called Virtual Systems for Immuno-Oncology (VISION), which is a human co-culture system of engineered primary T-cells that is “capable of mimicking patients’ tumor microenvironment and immune system,” Dr Joyce explained. “A key feature of this model is that the T-cells are preconditioned to mimic tumor-infiltrating lymphocytes through previous tumor cell exposures. The objective is to predict how immunologic or other types of interventions will perform in a patient, then apply that information to identify patients who are most likely to benefit and customize new treatments that will expand benefits.”

The co-culture system was maintained for 2 weeks to drive partial T-cell exhaustion. Cytotoxicity of these partially exhausted T-cells was measured against PD-L1/L2 double-positive, single-positive, or double-negative cancer cells in the presence of balstilimab, pembrolizumab (Keytruda), and nivolumab (Opdivo).

As expected, balstilimab enhanced T-cell killing against tumor cells expressing both PD-L1 and PD-L2. However, it also enhanced T-cell killing against PD-L1– and PD-L2–deficient tumor cells for one of two blood donors tested.

“These data indicate the potential activity of balstilimab regardless of PD-L1 status,” Dr Joyce said. “In summary, our results demonstrate the potential for differentiated activity of balstilimab in the clinic, with preliminary confirmation using our VISION platform,” she concluded.

FDA Approval Pending

In 2020, the FDA granted balstilimab a fast-track review for the treatment of patients with cervical cancer, as well as for use in combination with zalifrelimab, a CTLA-4 inhibitor, for patients with relapsed or refractory cervical cancer. The regimen of balstilimab plus zalifrelimab has shown superior overall response rates and longer duration of response compared with balstilimab alone.

In April 2021, based on these new study results, a new application was submitted to the FDA for balstilimab, for the treatment of patients with recurrent or metastatic cervical cancer. The FDA is expected to issue its final decision regarding the use of balstilimab for the treatment of patients with recurrent or metastatic cervical cancer in December 2021.

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