Mechanism of Action of Botensilimab and its Use in Ovarian Cancer

Bruno Bockorny, MD, assistant professor of medicine with Harvard Medical School and an attending physician in Gastrointestinal Oncology at Beth Israel Deaconess Medical Center, explains the mechanism of action of botensilimab (AGEN1181).

Bockorny also discusses what rationalizes the use of botensilimab in combination with balstilimab (AGEN2034) for the treatment of patients with ovarian cancer.

In the C-800 study, (NCT03860272), patients with platinum-resistant or refractory, metastatic disease received 1 mg/kg (29%) or 2 (71%) mg/kg of botensilimab every 6 weeks in addition to 3 mg/kg of balstilimab every 2 weeks. Those enrolled were allowed to have received prior immunotherapy, and crossover from prior botensilimab monotherapy was allowed.

Results from the ovarian cancer cohort of 64 patients had an objective response rate of 33% (95% CI, 15.6%-55.3%), including a complete response in 1 patient, 7 partial responses, 8 cases of stable disease, and 8 cases of progressive disease, at a median follow-up of 6.9 months (range, 1.7-29.2 months). Additionally, the disease control rate was 67% (44.7%-84.4%) and the median duration of response was not reached (4.2 months to not reached).

According to Bockorny, this experimental combination of botensilimab with balstilimab could provide this field a potential solution as currently, there is lack of effective therapies for patients with ovarian cancer.

Transcription:

0:08 | Botensilimab is a novel, multifunctional CTLA-4 antibody that was designed to extend the benefits of immunotherapy to patients who are immunologically cold and refractory to immunotherapy. What is unique about this drug is the FC portion of the antibody is enhanced. It has a structure that induces more memory immune cells.

0:46 | There is more downregulation of regulatory T cells and more priming of the T cells. Through this, we see an amplification of the immune responses. We, in this clinical trial, combined botensilimab with balstilimab, which is an antibody against PD-1.