A 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.

Abstract

TPS844 Background: Patients with advanced gastrointestinal (GI) malignancies have poor prognoses and limited treatment options. Cadherin 17 (CDH17) is a cell membrane-associated protein important for GI cell-cell interactions that is expressed in proximity to epithelial tight junctions. In some GI malignancies, CDH17 expression is also expressed diffusely across the cancer cell membrane, thus providing access to CDH17 directed CAR T-cells. CHM CDH17 is a third generation autologous CAR T-cell product candidate that was designed to target and eradicate CDH17+ solid tumors. Notably, expression of CDH17 varies across indications in the cancer setting CDH17– TABLE 1. Methods: Clinical Trial NCT06055439 is a seamless Phase 1/2 clinical trial of autologous CHM CDH17 CAR T-cells for patients with advanced gastric cancer (GC), colorectal (CRC) cancer or neuroendocrine tumors (NETs) of the midgut or hindgut. As CDH17 expression in GC is heterogenous, GC subjects will be screened for CDH17 expression. In preparation for receiving CDH17 CAR T-cells, subjects receive 3-days of lymphodepleting intravenous (IV) chemotherapy (fludarabine and cyclophosphamide). The Phase 1 portion of the clinical trial uses a 3+3 dose escalation and a starting dose of 50 million CAR-T cells in a single IV infusion. Decisions regarding dose escalation/de-escalation are based on real-time dose-limiting toxicity evaluation during the first 28 days of treatment during dose escalation. After establishing a recommended Phase 2 dose, three indication-specific Simon 2-Stage cohorts will be initiated in (1) GC (2) CRC and (3) NETs of the midgut or hindgut to further characterize the safety and assess the efficacy of CHM CDH17 CAR T-cells. This is an ongoing first-in-human multi-center clinical trial of CHM CDH17, a CDH17 directed autologous CAR T-cell product candidate, enrolling subjects with advanced GI cancers that express CDH17. Clinical trial information: NCT06055439 . Expression of CDH17 in selected gastrointestinal cancer indications. Indication Sample size CDH17Expression %* Colorectal cancer 821 96% Neuroendocrine tumors of the midgut and hindgut 119 97% Gastric cancer 1,409 64% *Expression of total tumors tested for CDH17 by immunohistochemistry (CHM data on file).