Botensilimab and Balstilimab Optimization in Colorectal cancer (BB-OPCO)

Summary:

Eighty-five percent of colorectal cancer (CRC) are Microsatellite stable (MSS). MSS CRC has had limited response to conventional immune checkpoint inhibitors (ICIs), especially those with liver metastasis. ICIs work by blocking cancer cells’ ability to hide themselves from cancer killing T-cells by targeting PD-1/PD-L1 and CTLA-4. ​CRC patients with liver metastasis have been shown to mitigate anti-tumor T-cell activity via suppressive macrophages, which may dimmish the response to current ICI strategies. Additionally, trials of ICIs in patients with MSS CRC have occurred in later lines of therapy, resulting in the ICIs being less effective due to cross resistance.​ This raises the concept that patients with MSS CRC who lack liver metastasis may have a favorable response to immunotherapy, particularly if they receive ICIs prior to other treatments.​Botensilimab is an enhanced ICI targeting CTLA-4 which has demonstrated an improved activity and side effect profile over other CTLA-4 targeting drugs. Botensilimab combined with balstilimab (an ICI targeting PD-1) exhibited a disease control rate of 73% in patients with MSS CRC who have been heavily pre-treated. ​The researchers hypothesize that patients with MSS CRC who lack metastasis to immune-privileged sites such as the liver, brain, and bone may respond well to first-line botensilimab/balstilimab. ​This phase I study will assess the feasibility, safety, tolerability, and response rate of first-line botensilimab in combination with balstilimab in patients with MSS CRC without liver, brain, or bone metastasis. Patients who progress will be treated with botensilimab/balstilimab in combination standard of care treatment.

Trial Registration: ClinicalTrials.gov Identifier: NCT06268015