FDA Clears NDA for Novel CDH17 CAR T-Cell Therapy in Advanced GI Cancer

"This is a critical step forward in developing an entirely new CAR T therapy for GI cancers and neuroendocrine tumors, providing new hopes for the patients [with cancer] who are refractory to the existing therapies," according to Xianxin Hua, MD, PhD.

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

CHM 2101 will be evaluated as part of a multi-center, open-label phase 1A/B trial in a population of patients who have been diagnosed with advanced colorectal cancer (CRC), gastric cancer, and neuroendocrine tumors.

“It is exciting to see the advancement from discovery of the CDH17 target and CAR T 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 Penn’s Perelman School of Medicine, as well as an investigator at the Abramson Family Cancer Research Institute, said in the press release. “This is a critical step forward in developing an entirely new CAR T therapy for GI cancers and neuroendocrine tumors, providing new hopes for the patients [with cancer] who are refractory to the existing therapies.”

Findings from a preclinical study assessing CHM 2101 in patients with neuroendocrine tumors and GI cancer indicated that the product was able to destroy established tumors across 7 models with no negative impact on healthy tissues.²

CHM 2102 is a novel third-generation, CAR T-cell product that targets CDH17, which is commonly known to be associated with worse outcomes and metastatic disease in those with select GI cancers, including CRC, gastric cancer, and neuroendocrine tumors.

Following the clearance of this application, investigators are now able to launch a phase 1/2 study (NCT06055439) in the aforementioned populations, with enrollment anticipated to begin in 2024.

The study’s primary outcomes are dose-limiting toxicities, cytokine release syndrome events, safety, and objective response rate. Key secondary outcomes will include disease control rate, time to response, duration of response, progression-free survival, and overall survival. The study will have patients undergo lymphodepletion with fludarabine and cytarabine for 3 days followed by a single infusion of CHM 2101.

To be included in the study, patients are required to have a histologic diagnosis of 1 or more solid tumors of a GI origin. Additional inclusion criteria include unstained archival tissue or new tumor biopsy and previous treatment with at least 1 previous line of systemic anti-cancer treatment in the locally advanced/metastatic setting. Those between the ages of 18 to 85 years with an ECOG performance status of 0 to 1 and a life expectancy of 12 weeks or more are eligible for enrollment.

Those who have previously undergone treatment with CDH17-target agents, unresolved adverse effects from previous treatments greater than grade 1, or uncontrolled seizure activity and/or central nervous system metastases are not eligible for the study. Additional exclusion criteria include liver involvement of 50% or more; active infection in need of oral or intravenous antibiotics; or diagnosis of pleural effusions, interstitial lung disease, or heart failure. Those who require ongoing treatment with corticosteroids or had a previous malignancy within 5 years of the study—with the exception of non-melanoma skin cancer or cervical cancer treated with curative intent—are unable to enroll on the study.

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. Chimeric Therapeutics. October 31, 2023. Accessed November 8, 2023. https://bit.ly/3FQmQED
2. Feng Z, He X, Zhang X, et al. Potent suppression of neuroendocrine tumors and gastrointestinal cancers by CDH17CAR T cells without toxicity to normal tissues. Nat Can. 2022;3:581-594. doi:10.1038/s43018-022-00344-7