Chimeric Therapeutics (ASX:CHM) has announced that its CHM CDH17 CAR-T program has advanced to Dose Level 3. This is the highest dose tier in the Phase 1 portion of its ongoing trial.
The escalation follows the successful completion of Dose Levels 1 and 2, where 50 million and 150 million CDH17 CAR-T cells were administered, respectively. Across these cohorts, no safety concerns or off-target effects were observed, reinforcing confidence in the therapy’s safety profile. Encouraged by these findings, Chimeric has now dosed the first patient in the 450 million-cell cohort, marking the final escalation step in Phase 1.
At Dose Level 1, one colorectal cancer (CRC) patient has maintained stable disease for 13 months following a single administration. At Dose Level 2, another CRC patient remains stable at nine months post-treatment. Notably, both patients remain on study without requiring additional therapies. Across all treated subjects, the engineered cells have demonstrated expansion and persistence in the bloodstream for up to 12 months. This is an indicator of durable biological activity.
To date, four patients have been treated at Dose Level 1 and five at Dose Level 2, with one additional patient pending. Eleven successful manufacturing runs have been completed, underscoring operational consistency alongside clinical progress.
The absence of off-tumour effects or gastrointestinal toxicity significantly reduces the program's risk at this stage, the company said.
The ongoing Phase 1/2 trial (NCT06055439) is designed to determine a recommended Phase 2 dose and evaluate safety and objective response rates in patients with advanced colorectal cancer, gastric cancer and intestinal neuroendocrine tumours. The Phase 1 component is expected to enrol up to 15 patients before transitioning into indication-specific expansion cohorts.
CHM CDH17 is a first-in-class, third-generation CAR-T therapy targeting CDH17, a biomarker associated with poor prognosis and metastasis in common gastrointestinal tumours. The program originated at the University of Pennsylvania in the laboratory of Dr Xianxin Hua. Preclinical data published in Nature Cancer in March 2022 demonstrated complete tumour eradication across seven cancer types in murine models, providing the scientific rationale underpinning the clinical development strategy.