CHM-2101, an autologous Cadherin 17 (CDH17) Chimeric Antigen Receptor (CAR-) T-cell therapy for the treatment of advanced gastrointestinal (GI) cancers that are relapsed or refractory to at least 1 standard treatment regimen in the metastatic or locally advanced setting, has been granted Fast Track Designation by the US Food and Drug Administration (FDA). The investigational drug is being developed by Chimeric Therapeutics while preclinical development was funded by the Neuroendocrine Tumor Research Foundation (NETRF).
Discovered at the University of Pennsylvania in the laboratory of Xianxin Hua, MD, Ph.D., CHM-2101 is a third generation, novel CAR-T cell therapy that targets CDH17, a cancer biomarker associated with poor prognosis and metastases in the most common gastrointestinal tumors. These tumors are often refractory to therapy after metastasis.
Preclinical study results for CDH17 CAR T were published by Hua and his colleagues in 2022 in Nature Cancer, demonstrating complete eradication of tumors in 7 types of cancer in mice.[1]
Improving outcomes
The Fast Track Designation was granted based on the FDA’s assessment of the potential of the investigational drug to improve outcomes for patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) who have progressed beyond at least one prior line of therapy in the advanced or metastatic setting.
This designation recognizes the potential of this new treatment to address the unmet medical need for additional therapies for GEP-NETs. a first-in-class, 3rd generation CDH17 CAR T-cell therapy invented
Fast Track Designation is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need.
This designation by the US FDA is intended to get important new drugs to patients earlier. With this designation, Chimeric will have increased FDA interactions that include more frequent meetings with the FDA to discuss the drug’s development plan, more frequent written communication from the FDA, and potential eligibility for Accelerated Approval, Priority Review and Rolling BLA 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,” said Jason B Litten MD, Chief Medical Officer at Chimeric Therapeutics.
“It is deeply gratifying to see the scientific research that NETRF has supported at The University of Pennsylvania since 2014 is now in the clinic and being recognized for its potential as an effective treatment for neuroendocrine tumor patients,” added Elyse Gellerman, MHS, Chief Executive Officer of the Neuroendocrine Tumor Research Foundation said,
Development
The Phase 1/2 clinical trial (NCT06055439) is a two-stage study designed to determine a recommended Phase 2 dose of CHM CDH17 and evaluate its safety and objective response rate in patients with advanced colorectal cancer, gastric cancer, and intestinal neuroendocrine tumors (NETs).
The Phase 1 portion of this study is expected to enroll up to 15 patients and lead to dose selection and expansion with indication-specific Phase 2 cohorts. Five patients have been treated so far. In addition to the University of Pennsylvania, the trial is open at the University of Chicago, Sarah Cannon Research Institute, and Emory University Winship Cancer Center.
“We are gaining significant momentum on CHM CDH17 and look forward to our interactions with the FDA to get our advanced therapy to patients in need,” said Rebecca McQualter, MD, the Chief Executive Officer of Chimeric Therapeutics.
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Clinical trials
A Phase 1/2 Study to Evaluate CHM-2101, an Autologous Cadherin 17 Chimeric Antigen Receptor (CAR) T Cell Therapy – ClinicalTrials.gov ID NCT06055439
Reference
[1] Feng Z, He X, Zhang X, Wu Y, Xing B, Knowles A, Shan Q, Miller S, Hojnacki T, Ma J, Katona BW, Gade TPF, Siegel DL, Schrader J, Metz DC, June CH, Hua X. Potent suppression of neuroendocrine tumors and gastrointestinal cancers by CDH17CAR T cells without toxicity to normal tissues. Nat Cancer. 2022 May;3(5):581-594. doi: 10.1038/s43018-022-00344-7. Epub 2022 Mar 21. Erratum in: Nat Cancer. 2024 Apr;5(4):691. doi: 10.1038/s43018-024-00766-5. PMID: 35314826.
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