Cervical cancer is the fourth leading cause of cancer death among women worldwide. Statistics show that women aged 35-44 are most frequently diagnosed with cervical cancer. This disease is usually curable when detected early and treated effectively, but treatment options are more limited in later stages. Recently, the U.S. FDA accepted the Biologics License Application (BLA) for the PD-1 antibody Balstilimab and granted it priority review status. This drug is intended for the treatment of patients with recurrent or metastatic cervical cancer whose disease has progressed during or after chemotherapy.
Balstilimab drug introduction
Drug name: Balstilimab
Other names: AGEN2034
Developer: Agenus
Consultant: United Cancer Center
Balstilimab is a novel fully human monoclonal immunoglobulin G4 (IgG4) designed to block the interaction between PD-1 (programmed cell death protein 1) and its ligands PD-L1 and PD-L2. PD-1 is a negative regulator of immune activation and is considered a fundamental target in the immuno-oncology market. Balstilimab is currently undergoing clinical trials as monotherapy and in combination with the anti-CTLA-4 antibody zalifrelimab in a Phase II clinical trial for the treatment of recurrent/metastatic cervical cancer. In April 2020, the FDA granted the PD-1 inhibitor Balstilimab Fast Track designation for the treatment of patients with advanced cervical cancer.
Balstilimab research data
The Balstilimab BLA submission is based on updated data presented at the 2020 ESMO online meeting. The Phase II clinical trial (NCT03894215) is a multicenter international trial enrolling 161 patients. Enrolled patients received 3 mg/kg of Balstilimab every 3 weeks for 24 months. In subsequent phases of the trial, researchers performed imaging examinations every 6 weeks for 2 years. The primary endpoint was the objective response rate (ORR) assessed according to the independent review committee and RECIST v1.1 criteria. Secondary endpoints were duration of response (DOR), progression-free survival (PFS), and overall survival (OS).
Data presented at the conference showed that, in the modified intention-to-treat (mITT) population (n=160) and 13% (n=18; 95% CI, 8%–20%), Balstilimab monotherapy achieved an optimal overall response rate (ORR) of 14% (n=23; 95% CI, 10%–21%) in a subset of patients who had received at least one or more lines of chemotherapy. The duration of response (DOR) with Balstilimab lasted 15.4 months in both groups.
In the mITT population, 3 patients reported complete remission (CR) and 20 patients reported partial remission (PR). The objective response rate (ORR) was 19.0% (95% CI, 13%–28%) in PD-L1-positive patients and 10.0% (95% CI, 4%–22%) in patients without PD-L1 expression. Among participants who had received at least one or more chemotherapy regimens, 3 patients achieved CR and 15 achieved PR. In this group, the ORR was 18.0% (95% CI, 11%–27%) in PD-L1-positive patients and 8.0% (95% CI, 3%–21%) in patients without PD-L1 expression.
Regarding safety, the most frequently reported adverse events (AEs) were systemic disturbances and administration site conditions, occurring in 33.5% (n=54) of patients treated with Balstilimab; one patient experienced this at grade 3 or higher. Furthermore, gastrointestinal toxicities of all grades were observed in 25.5% (n=41) of patients, while hematologic and lymphatic disturbances of all grades occurred in 14.3% (n=23) of patients.
Specifically, regarding immune-related adverse events, 5.6% (n=9) of patients experienced gastrointestinal disorders, 5.6% (n=9) experienced laboratory abnormalities, and 5.0% (n=8) experienced endocrine disorders. Treatment-related immunotherapy adverse events included gastrointestinal disorders (3.1%; 5 cases), laboratory abnormalities (1.2%; n=2), and skin and soft tissue disorders (0.6%; n=1).
A friendly reminder: Women with recurrent or metastatic cervical cancer have a poor prognosis and limited treatment options. However, trial results demonstrate that Balstilimab has the potential to address unmet medical needs in cervical cancer patients, potentially becoming a new treatment option for these patients. We look forward to the early approval of this new drug and its rapid clinical application, benefiting more cancer patients.
