Data presented at the plenary session of the annual Society of Gynecologic Oncology Meeting in March 2023 suggests that combined immunotherapy with botensilimab and balstilimab produces durable responses in advanced ovarian cancer. “These results add to the growing body of data showing deep and durable efficacy signals for botensilimab across nine cold and treatment-resistant cancers,” said Steven O’Day, M.D., Chief Medical Officer of Agenus. “Botensilimab is designed with a unique mechanism of action that stimulates both innate and adaptive immune responses against cancer, resulting in an improved benefit compared to what has been reported for other checkpoint therapies.”
About Botensilimab
Botensilimab is an Fc-enhanced CTLA-4 antibody. In addition to blocking the interaction of CTLA-4, the enhanced Fc portion of the drug has several unique properties, such as increased frequency of dendritic cell concentration, a boost in T-cell formation, T-cell memory formation, T-cell priming, and enhanced T-reg depletion. Balstilimab is an IgG4, anti–PD-1 antibody with a similar profile to other anti–PD-1 agents (Keytruda, Opdivo etc).
Ovarian cancer has long been considered to be a “cold tumor” that is not likely to trigger a strong immune response making current immunotherapy drugs ineffective. Cold tumors tend to be surrounded by cells that are able to suppress the immune response and keep T cells (a type of immune cell) from attacking the tumor cells and killing them. Cold tumors usually do not respond to treatment with immunotherapy. mImmunotherapy has been considered ineffective in ovarian cancer producing response in less than 10% of advanced patients.
Botensilimab, as compared with the earlier anti–CTLA-4 agents is a multifunctional CTLA-4 agent. In addition to binding the CTLA-4, botensilimab also had some point mutations in the Fc region that increase the binding to some receptors in the antigen-presenting cells and natural killer cells. These “activating” Fc gamma receptors engage other immune cells and trigger better immune responses than other first-generation CTLA-4 agents.
The current study evaluated the novel immunotherapy combination in 24 patients as part of an expansion Phase 1b clinical trial in patients with recurrent platinum resistant/refractory ovarian cancer. Overall, one in three patients responded to treatment and reported side effects were minimal.
References
- Bockorny B, Matulonis UA, O’Day SJ, et al. Botensilimab, a novel innate/adaptive immune activator, plus balstilimab (anti–PD-1) in patients with recurrent platinum refractory/resistant ovarian cancer. Presented at: 2023 SGO Annual Meeting on Women’s Cancer; March 25-28, 2023; Tampa, Florida.
- Results from a phase 1a/1b study of botensilimab (BOT), a novel innate/adaptive immune activator, plus balstilimab (BAL; anti-PD-1 antibody) in metastatic heavily pretreated microsatellite stable colorectal cancer (MSS CRC). J Clin Oncol. 2023;41(suppl 4; abstr LBA8). https://10.1200/JCO.2023.41.4_suppl.LBA8
