Cervical cancer is the fourth leading cause of cancer death among women in the world. Relevant statistics show that women aged 35-44 are most often diagnosed with cervical cancer. This disease is usually curable when it is detected at an early stage and effectively treated, but treatment options in the late stage are more limited. Recently, the U.S. FDA has accepted the biological product license application (BLA) for the PD-1 antibody Balstilimab and granted priority review qualifications. The drug is used to treat patients with recurrent or metastatic cervical cancer who have 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).
Warm reminder: Female patients with recurrent or metastatic cervical cancer have a poor prognosis and limited treatment options, but the trial results have proved that Balstilimab has the potential to solve the unmet medical needs of cervical cancer patients, and it is expected to become a brand new treatment option for such patients. It is hoped that this new drug will be approved as soon as possible and will be used in clinical practice as soon as possible for the benefit of more cancer patients.
