Botensilimab-Balstilimab Showed Durable Responses for Metastatic Microsatellite Stable Colorectal Cancer

Updated Efficacy and Safety Data from a Phase 1b Study

At the 2023 World Congress on Gastrointestinal Cancers, Andrea Bullock, MD,  Beth Israel Deaconness Medical Center, Harvard Medical School, Boston, Massachusetts, shares results from an expanded phase 1 trial evaluating botensilimab plus balstilimab for patients with heavily pretreated, metastatic microsatellite stable colorectal cancer.

Dr Bullock stated, "We have been encouraged by the responses seen in this heavily pretreated population of patients with microsatellite stable colorectal cancer, both those with and without liver metastasis."

Transcript:

Hi, I'm Andrea Bullock and I am here at the 2023 World Congress on Gastrointestinal Cancers. I am here presenting the results from an expanded phase 1 trial of botensilmab, a novel anti-CTLA-4 and balstilimab, a PD-1 inhibitor in patients with microsatellite stable colorectal cancer.

Microsatellite stable colorectal cancer is a disease that has, to date, been refractory to most of the available immuno-oncology agents, but comprises the majority of patients with that disease. This study was conducted in patients with heavily pretreated, microsatellite stable colorectal cancer, and patients received a combination of these two immunotherapy agents.

Botensilimab is a novel anti-CTLA-4. It was designed to increase T-cell activation as well as reduction of T-regulatory cells and has a unique FC-enhanced portion of the antibody, which increases its binding to an APC and NK cells. And this has led to, we believe, increased efficacy in what have historically been considered cold or immune refractory tumors, and also a decrease in some of the immune related toxicities that are more commonly seen with other immune therapies.

Our study included 101 patients in the intent to treat population, and 87 patients in the efficacy evaluable population. We have seen impressive deep and durable responses in that population, among patients without liver metastases in their colorectal cancer, with a response rate of 23% and an estimated 12-month survival of 74%. The median overall survival in our subjects was 20.9 months overall.

The adverse event profile has been similar to what's been reported with this combination previously, but interestingly, the toxicity seemed to be confined primarily to the GI tract. Diarrhea/colitis has been the most prominent side effect that we have seen. The diarrhea/colitis has been reversible with early intervention. And visceral toxicities have been very minimal with this combination.

In addition, there has been stable disease seen in a large number of patients, and so even in the absence of a resist response, the survival estimates have been encouraging across the population, including both those with and without liver metastases.

Overall, we have been encouraged by the responses seen in this heavily pretreated population of patients with microsatellite stable colorectal cancer, both those with and without liver metastasis, and are excited to move this combination forward in a phase 2 trial that is accruing present. Thank you so much for your time.

Source:

Bullock A, Fakih M, Gordon M, et al. Results from an expanded phase 1 trial of botensilimab (BOT), a multifunctional anti-CTLA-4, plus balstilimab (BAL; anti-PD-1) for metastatic heavily pretreated microsatellite stable colorectal cancer (MSS CRC). Presented at the 2023 World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain. Abstract LBA-4