Clinical and translational results from the phase 1 portion of the phase 1/2 study to evaluate CHM-2101, an autologous cadherin 17 (CDH17) chimeric antigen receptor (CAR) T cell therapy for the treatment of relapsed or refractory gastrointestinal cancers.

2536 Background: CHM-2101 is a Cadherin 17 directed autologous CAR T-cell product being developed to address the continuing unmet medical need for effective therapy against relapsed or refractory gastrointestinal (GI) cancers. Solid tumors of the GI tract such as gastric cancer, colorectal cancer (CRC) and neuroendocrine tumors (NETs) are devastating diseases associated with poor outcomes and more than 1.3 million global deaths annually. Despite advances in surgical and medical treatment of these solid tumors, the prognosis for patients with relapsed or refractory disease remains poor. There remains a need for innovative and effective treatments for patients with advanced and treatment-recalcitrant GI malignancies. Methods: The ongoing clinical trial is a seamless Phase 1/2 study enrolling subjects with gastric cancer, CRC or NETs of the midgut or hindgut. Enrolled subjects undergo screening and apheresis to enable manufacturing of CHM-2101. After completing apheresis, bridging therapy is permitted to provide disease control. After confirming successful CHM-2101 manufacturing and washout of bridging therapy, study subjects receive 3 days of lymphodepleting chemotherapy (fludarabine 30mg/m2/day and cyclophosphamide 500mg/m2/day). After two days of rest, subjects receive a one-time IV infusion of CHM-2101. Results: As of October 24, 2025, 13 subjects have been enrolled with 2 screen failures. Eleven of eleven successful manufacturing runs enabled treatment of 9 subjects to date (4 subjects at Dose Level 1 and 5 subjects at Dose Level 2). Most AEs were Grade 1-2. Aside from lymphodepleting chemotherapy-related cytopenias, Grade 3 Treatment-Related Adverse Events (TRAEs) were Cytokine Release Syndrome (CRS) and Enterocolitis in 1 subject each. There have been no Grade 4 or 5 TRAEs or DLTs. After IV infusion, CHM-2101 was noted to expand and persist (by flow and ddPCR) in the peripheral blood of all treated subjects. Conclusions: CHM-2101 has demonstrated cellular expansion and persistence with clinical tolerability in study subjects with advanced GI cancers at two dose levels. Enrollment of patients at Dose Level 3 is ongoing at US Cancer Centers. Clinical trial information: NCT06055439 .