Substantial Benefit Shown With Botensilimab/Balstilimab in Ovarian Cancer

Bruno Bockorny, MD

There is an immense need for new therapies to treat ovarian cancer, according to Bruno Bockorny, MD. Although immunotherapy exists for ovarian cancer treatment, the response rates have been low.

The experimental combination of botensilimab (AGEN1181) and balstilimab (AGEN2034) could be the solution for the lack of effective therapies in the field. According to Bockorny, assistant professor of medicine with Harvard Medical School and an attending physician in Gastrointestinal Oncology at Beth Israel Deaconess Medical Center, results from an ovarian cancer cohort of the study botensilimab/ balstilimab (C-800 study, NCT03860272) were impressive.

“The numbers we observed are substantially higher than what we would expect for a traditional combination immunotherapy. The response rate to immunotherapy in patients with ovarian cancer is between 3% and 10%,” Bockorny told Targeted Oncology™, in an interview.

The ovarian cancer cohort of the study included 64 patients with ovarian cancer who had a median age of 64 years (range, 37-75 years). At a median follow-up of 6.9 months (range, 1.7-29.2 months), the objective response rate was 33% (95% CI, 15.6%-55.3%), which included a complete response in 1 patient, 7 partial responses, 8 cases of stable disease, and 8 cases of progressive disease. The disease control rate was 67% (44.7%-84.4%) and the median duration of response was not reached (4.2 month to not reached).

In the interview, Bockorny discussed background and key takeaways from the phase 1 C-800 study.

TARGETED ONCOLOGY: Can you explain the mechanism of action of botensilimab and what rationalizes its use in combination with balstilimab for ovarian cancer treatment?

Bockorny: 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 any structure that induce more memory immune cells. 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.

Can you discuss the study design?

The C-800 trial is a phase 1b clinical trial. It's a very large study that enrolled patients with any solid tumors with disease progression after standard-of-care treatment options including, investigational options and immunotherapy options. This study started with a monotherapy phase with botensilimab at a lower dose, followed by that combination with balstilimab. Now, we are in the final phases with disease specific expansion cohorts.

At [the Society of Gynecologic Oncology [SGO] 2023 Annual Meeting on Women’s Cancer] this year, we presented data of patients with ovarian cancer who were platinum resistant or refractory.

What should an oncologist takeaway from this study?

In this population of their patients with ovarian cancer, we presented the data on 24 patients. What's key here is that this patient population has been heavily pretreated and they had a median 4 prior lines of therapy. About 20% of them had previously received immunotherapy. In this heavily pretreated population, the numbers we observed were substantially higher than what we would expect for a traditional combination immunotherapy. The response rate to immunotherapy in patients with ovarian cancer is between 3% and 10%.

I think the key highlights are that the objective response rate that we're seeing this heavily pretreated population is higher than what we would expect for traditional immunotherapy combination. We are also seeing that the safety profile has been comparable to what we would expect for traditional immunotherapy. I think what's also unique with this combination is that we are seeing very little high-grade visceral toxicity outside the gastrointestinal tract. That is unique for this combination and good for our patients.

The trial is ongoing, so we continue to enroll patients with ovarian cancer, as well as endometrial cancer.

What other exciting data were presented during SGO?

I was excited to see my colleagues discussing novel targets for immunotherapy during the same plenary session. I'm hopeful to see immunotherapy moving forward in ovarian cancer. It's a tumor type for which immunotherapy has not helped. We urgently need better treatment options for these patients.

_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.}