The purpose of this study is to study the safety and effects of two new immunotherapies aimed at achieving and maintaining tumor shrinkage in patients with non-microsatellite stable colorectal cancer without liver metastases.

Botensilimab (also known as AGEN1181) and balstilimab (also known as AGEN2034) are both experimental drugs, which means that neither have been approved by the U.S. Food and Drug Administration (FDA).

There are currently no approved immunotherapies for patients with non-microsatellite stable colorectal cancer without liver metastases. For patients whose disease has progressed following approved chemotherapies and biologic agents, approved options are limited and it is rare that tumors shrink in response to these therapies, or for patients who receive them to survive long-term.   

Participants will be placed into one of five groups. Each of the five groups will receive a different combination and different dosages of the study drugs. The study team will discuss what group and dose each participant is assigned to. 

Botensilimab and balstilimab are administered intravenously through an IV in a vein.

The five groups will receive the following study drugs:

• Group A: Botensilimab 75 mg once every 6 weeks PLUS balstilimab 240 mg once every 2 weeks
• Group B: Botensilimab 150 mg once every 6 weeks PLUS balstilimab 240 mg once every 2 weeks 
• Group C: Botensilimab 75 mg once every 6 weeks
• Group D: Botensilimab 150 mg once every 6 weeks
• Group E: Standard of care chosen by the study doctor between one of two FDA approved medications, regorafenib or trifluridine and tipiracil. These medications are taken orally.

Participants should expect to take part in this study for approximately 2 years.