FDA Accepts IND for Novel CDH17-Targeted CAR T-Cell Therapy for Advanced Gastrointestinal Cancers

The FDA has cleared the investigational new drug application for CHM 2101, a novel CDH17-targeted CAR T-cell therapy, for the treatment of patients with gastrointestinal (GI) cancers, according to an announcement from Chimeric Therapeutics.¹

CDH17 is associated with poor prognosis and metastasis in the most common GI cancers, including colorectal cancer (CRC), gastric cancer, and neuroendocrine tumors (NETs). Preclinical studies showed that CHM 2101 successfully eradicated established tumors in 7 cancer models without toxicity to normal tissues.

CHM 2101 will be investigated in a phase 1/2 trial (NCT06055439), which will include patients with advanced CRC, gastric cancer, and NETs.

“It is exciting to see the advancement from discovery of the CDH17 target and CAR T-cell therapy in preclinical studies to the initiation of clinical trials in patients with GI-cancers and neuroendocrine tumors," Xianxin Hua, MD, PhD, professor of cancer biology at Perelman School of Medicine at the University of Pennsylvania, an investigator at the Abramson Family Cancer Research Institute, and a Harrington Scholar Innovator, stated in a news release. “This is a critical step forward in developing an entirely new CAR [T-cell] therapy for [patients with] GI cancers and NETs, providing new hopes for the [patients with] cancer who are refractory to the existing therapies.”

The phase 1/2 study will enroll patients between 18 and 85 years of age with a confirmed histologic diagnosis of gastric adenocarcinoma, colon and/or rectal adenocarcinoma, and grade 1/2 or well-differentiated grade 3 NETs of the midgut and hindgut. Notably, patients with gastric adenocarcinoma will need to have central laboratory confirmation of CDH17-positive tumor expression of at least 5 by immunohistochemistry.²

At least 1 prior line of systemic anticancer treatment in the locally advanced or metastatic setting is required, and patients must have exhausted or declined all available FDA-approved treatment options, including targeted therapies. Other key inclusion criteria consist of an ECOG performance status of 0 or 1, a life expectancy of at least 12 weeks, and a left ventricular ejection fraction of at least 50%.

Patients will be excluded if they received prior CDH17-targeted therapies; have uncontrolled seizure activity and/or known central nervous system metastases; have liver involvement of at least 50%; or are ongoing treatment with systemic corticosteroid therapy with prednisone at doses of at least 20 mg per day or equivalent treatment with another agent.

Patients will receive lymphodepletion with fludarabine and cyclophosphamide for 3 days prior to receiving a single infusion of CHM 2101.

Dose-limiting toxicities, incidence of cytokine release syndrome, safety, and objective response rate will serve as the trial’s primary end points. Secondary end points include disease control rate, time to response, duration of response, progression-free survival, and overall survival.

Patient enrollment is expected to begin in 2024.¹

“I am really excited about the planned phase 1 clinical trial of CHM 2101 and the opportunity to bring a potentially transformative new investigational agent to cancer patients who need them most,” Michael R. Bishop, MD, professor of medicine and director of the David and Etta Jonas Center for Cellular Therapy at the University of Chicago, added in the news release.

References

1. Chimeric Therapeutics announces FDA clearance of IND application for CHM 2101, a novel CDH17 CAR T cell therapy for advanced gastrointestinal cancers. News release. October 31, 2023. Accessed November 6, 2023. https://chimerictherapeutics.com/wp-content/uploads/2023/10/CHM2101IND-103023.pdf
2. A phase 1/​2 study to evaluate CHM-2101, an autologous cadherin 17 chimeric antigen receptor (CAR) T cell therapy. ClinicalTrials.gov. Updated September 26, 2023. Accessed November 6, 2023. https://clinicaltrials.gov/study/NCT06055439