This Phase 2 clinical study will evaluate evorpacept (ALX148) in combination with cetuximab and pembrolizumab for refractory microsatellite stable metastatic colorectal cancer

This is an open-label, multi-center, single-arm phase II clinical trial (with safety run-in) evaluating the combination of evorpacept (ALX148), cetuximab, and pembrolizumab in patients with metastatic microsatellite stable colorectal cancer who have progressed on at least 2 lines of systemic therapy. A subset of patients will undergo study-related biopsies. There will be a safety run-in stage followed by a dose expansion stage. Patients in both stages will continue to receive study therapy until disease progression according to RECIST v1.1.

Inclusion Criteria:

To be eligible to participate in this study, an individual must meet all of the following criteria:

• Have a diagnosis of metastatic colorectal cancer previously treated with at least two lines of therapy for unresectable/metastatic disease
• Have microsatellite stable disease
• Adequate hematologic and end organ function

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

• Patients with known MSI-high status or known mismatch repair deficiency (dMMR)
• Patients in whom both mismatch repair and microsatellite stability status are unknown
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to any of the study medications or their classes
• Left-sided (at or distal to the splenic flexure) RAS/BRAF wild-type metastatic colorectal cancer who are EGFR inhibitor naïve.
• Prior therapy with an anti-PD-1, anti-PD-L1, anti PD L2, anti-CD47, or anti-SIRPα agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137)