FDA Grants Fast Track Designation to CHM CDH17 for Gastroenteropancreatic NETs

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Ashling Wahner & MJH Life Sciences Using AI

The FDA has granted fast track designation to CDH17 (CHM-2101 CAR T cells) for the treatment of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs).1

The designation was based on the FDA’s evaluation of CHM CDH17’s ability to improve outcomes for patients with GEP-NETs whose disease progressed on at least 1 prior line of therapy in the advanced or metastatic setting.

With this designation, Chimeric, the developer of the agent, will have access to more frequent meetings with the FDA to discuss the development plan for CHM CDH17, more frequent written communication from the FDA, and potential eligibility for accelerated approval, priority review, and rolling biologics license application review.

“We are thrilled to announce that the US FDA has granted this designation and acknowledged the important unmet need that CHM CDH17 may serve for patients with GEP-NETs,” Jason B. Litten, MD, chief medical officer at Chimeric, stated in a news release.

CDH17 is an oncogenic biomarker that is associated with poor prognosis and metastases in select types of gastrointestinal tumors. CHM CDH17 is a third-generation, novel CDH17-directed CAR-T cell therapy that has previously shown complete eradication of CDH17-expressing NETs and gastric, pancreatic, and colorectal cancers in either tumor xenograft or autochthonous mouse models.1,2

The agent is now under evaluation in an ongoing, two-stage phase 1/2 trial (NCT06055439) in patients with advanced colorectal cancer, gastric cancer, and intestinal NETs.1 The phase 1 portion of the study will enroll up to 15 patients. Confirmation of the recommended phase 2 dose of CHM CDH17 will lead to phase 2 expansion in indication-specific cohorts.

“It is really gratifying to see scientific research that NETRF [Neuroendocrine Tumor Research Foundation] has supported at The University of Pennsylvania since 2014 is now in the clinic and is being recognized for its potential to be an effective treatment for [patients with] neuroendocrine tumor[s],” Elyse Gellerman, MHS, chief executive officer of NETRF said in a news release.

To be eligible for enrollment in the study, patients must have a confirmed histologic diagnosis of either gastric adenocarcinoma with central confirmation of CDH17-positive tumor expression, colon and/or rectal adenocarcinoma, or grade 1 or 2, or well-differentiated grade 3 NETs of the midgut and hindgut (ileal, jejunal, cecal, distal colonic, or rectal; with ≤ 55% Ki67 expression).3

Patients must also have unstained tumor tissue slides from archived tumor tissue or a new tumor biopsy, if medically feasible; received at least 1 prior line of systemic anticancer therapy in the locally advanced or metastatic setting; have an ECOG performance status of 0 or 1; have a life expectancy of at least 12 weeks; and have no known contraindications to leukapheresis, cyclophosphamide, fludarabine, or steroids.

Eligible patients will undergo leukapheresis to collect peripheral blood mononuclear cells for product manufacturing. A second attempt at leukapheresis may be allowed for patients who have an initial leukapheresis or manufacturing failure.

Notably, bridging chemotherapy will be allowed to ensure stable disease during CHM-2101 manufacturing. However, bridging chemotherapy will be prohibited within 2 weeks prior to leukapheresis and 2 weeks prior to planned CHM-2101 infusion.

Eligible patients will undergo 3 daily doses of intravenous (IV) fludarabine and cyclophosphamide before receiving a single IV dose of CHM-2101. The study’s primary outcome measures include dose-limiting toxicity, rates and grades of cytokine release syndrome, all other adverse effects, and objective response rate. Secondary outcome measures include traditional efficacy end points like disease control rate, time to response, duration of response, progression-free survival, and overall survival.

“We are gaining significant momentum [with the development of] CHM CDH17 and look forward to our interactions with the FDA to get our advanced therapy to patients in need,” Rebecca McQualter, PhD, chief executive officer of Chimeric, concluded in the news release.1

References

1. CHM CDH17 receives FDA fast track. News release. Chimeric Therapeutics. June 4, 2025. Accessed June 12, 2025. https://app.sharelinktechnologies.com/announcement/asx/a7db7fe3e622ec50cb7de1fce98e5b79
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 Cancer. 2022;3(5):581-594. doi:10.1038/s43018-022-00344-7
3. A phase 1/2 study to evaluate CHM-2101, an autologous cadherin 17 chimeric antigen receptor (CAR) T cell therapy. Clinicaltrials.gov. Updated April 27, 2025. Accessed June 12, 2025. https://clinicaltrials.gov/study/NCT06055439