Botensilimab Plus Balstilimab Shows Promise For Microsatellite Stable Metastatic Colorectal Cancer

Novel immunotherapy combination of botensilimab, a novel anti-CTLA-4 antibody, plus balstilimab, an anti-PD-1 antibody, demonstrated deep objective responses and evidence of durability in a cohort of heavily pretreated patients with microsatellite stable (MSS) metastatic colorectal cancer (CRC), according to a phase 1a/b study.

Anthony El-Khoueiry, MD, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, presented these findings at the 2022 ESMO World Congress on Gastrointestinal Cancer.

There is a “significant unmet need,” for the treatment of patients with MSS CRC, Dr El-Khoueiry stated, as the current standard of care approach “have low response rates and modest survival benefit.”

This analysis included 41 patients with heavily pretreated MSS CRC. The median number of prior lines of therapy was 4, with 34% who had previously been treated with immunotherapy. Patients received botensimilab at either 1 or 2 mg/kg every 6 weeks plus balstilimab at 3 mg/kg every 2 weeks. The primary and secondary end points included incidence of adverse events, objective response rate (ORR), and disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

The median follow up was 5.8 months. The ORR was 24%, and the DCR was 73%. The DOR ranged from 0 to 17+ months. In those patients who had no history of liver metastases or who had no recurrence after resection or ablation of liver metastases (n = 24), the ORR was 42% and the DCR was 96%. In those patients who responded, metastatic sites included soft tissue, peritoneum, retroperitoneum, pleural effusions, bone, lungs, and lymph nodes.

The combination had a favorable safety profile, with most adverse events (AEs) reported as grade 1 or 2 and no reported incidences of hypophysitis. Grade 3 treatment-related AEs occurred in 24% of patients. There were no grade 4 or 5 treatment-related AEs reported. The only grade 3 treatment-related AE that occurred in more than 1 patient was diarrhea/colitis. Botensilimab was discontinued in 8 (20%) patients, and botensilimab plus balstilimab was discontinued in 4 (10%) patients, due to a treatment related AE.

“[Botensilimab plus balstilimab] demonstrates unprecedented activity for immunotherapy in heavily pretreated patients with metastatic MSS CRC and manageable safety, consistent with its design,” concluded Dr El-Khoueiry and colleagues, adding “The ORR and DOR, including compelling efficacy in patients without liver metastases, are informing phase 2/3 study designs.”
 

Source:

Bullock A, Grossman J, Fakih M, et al. Botensilimab, a novel innate/adaptive immune activator, plus balstilimab (anti-PD-1) for metastatic heavily pretreated microsatellite stable colorectal cancer. Presented at: ESMO World Congress on Gastrointestinal Cancer; June 29-July 2, 2022. Barcelona, Spain. Abstract LBA O-9.