Chimeric Therapeutics Escalates CDH17 Trial to 450M Cells After Clean Safety Data
Chimeric Therapeutics advances CHM CDH17 trial to highest dose level
Chimeric Therapeutics (ASX: CHM) has escalated its Chimeric Therapeutics CHM CDH17 trial to Dose Level 3, administering 450 million CAR-T cells to the first patient in this cohort. The dose escalation follows completion of Dose Levels 1 and 2 with no safety concerns or off-target effects observed, concluding the Phase 1 portion of the study.
The trial (NCT06055439) targets advanced gastrointestinal cancers including colorectal cancer, gastric cancer, and intestinal neuroendocrine tumours. CHM CDH17 represents a first-in-class therapy targeting CDH17, a cancer biomarker associated with poor prognosis and metastases in common gastrointestinal tumours.
For investors, the clean dose escalation without safety issues represents clinical de-risking and progression toward Phase 2 dose selection. The achievement establishes a foundation for evaluating therapeutic responses at the highest planned dose level.
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What is CDH17 and why does targeting it matter for cancer treatment
CDH17 is a cancer biomarker linked to poor prognosis and metastatic spread in gastrointestinal tumours. The protein’s expression in these common cancers makes it an attractive therapeutic target for engineered immune cell therapies.
CAR-T therapy involves reprogramming a patient’s own immune cells to recognise and attack cancer cells expressing specific markers. The cells are extracted, genetically modified to carry a chimeric antigen receptor (CAR), then reinfused into the patient where they seek and destroy target cancer cells.
CHM CDH17 is a 3rd generation CAR-T therapy, incorporating the latest engineering advances to enhance cell function and persistence. This generational classification refers to the number of co-stimulatory domains built into the CAR construct, which influence how effectively the engineered cells activate and sustain their anti-cancer activity.
Solid tumours have historically presented challenges for CAR-T therapies, which have achieved remarkable success in blood cancers but struggled to penetrate and persist within solid tissue environments. The gastrointestinal cancer focus addresses both a significant unmet medical need and a large addressable market, given the prevalence of colorectal and gastric cancers globally.
For investors, the first-in-class targeting of CDH17 represents a differentiated approach in the competitive CAR-T landscape. Success in solid tumours could position Chimeric within a market segment where effective CAR-T therapies remain scarce.
Early clinical signals show disease control and exceptional cell persistence
The Chimeric Therapeutics CHM CDH17 trial has demonstrated compelling durability from single doses at lower dose levels. One colorectal cancer patient has maintained stable disease for 13 months following a single dose at Dose Level 1 (50 million cells), whilst another colorectal cancer patient has achieved ongoing stable disease at 9 months from a single dose at Dose Level 2 (150 million cells).
Both patients continue on study without requiring additional therapies during this period. CAR-T cells have been detected in patients’ blood for more than 12 months, indicating exceptional persistence of the engineered cells. The company has completed 11 successful manufacturing runs to date.
The safety profile remains clean, with no evidence of off-tumour effects or gastrointestinal toxicity observed. This absence of on-target, off-tumour toxicity is particularly significant given that CDH17 expression occurs in normal gastrointestinal tissue, though at lower levels than in tumours.
| Dose Level | Cell Count | Patients Treated | Key Observation |
|---|---|---|---|
| 1 | 50 million | 4 | 13-month stable disease (CRC) |
| 2 | 150 million | 5 (+1 pending) | 9-month stable disease ongoing (CRC) |
| 3 | 450 million | 1 (first patient) | Recruiting |
For investors, extended disease control from single doses at lower dose levels suggests potential for stronger responses at the therapeutic dose. The 12-month persistence indicates a durable mechanism of action, reducing the need for repeat dosing and potentially improving the therapy’s commercial viability.
CEO perspective on dose escalation milestone
Dr Rebecca McQualter, CEO, Chimeric Therapeutics
“Given what we’ve seen to date at much lower doses, we are particularly eager to see the response from Dose Level 3 in patients, which will conclude the Phase 1 portion of this study.”
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Trial structure and path to Phase 2
The Phase 1/2 study follows a two-stage design. Phase 1 establishes the recommended Phase 2 dose through dose escalation, whilst Phase 2 evaluates safety and objective response rate in indication-specific cohorts.
The trial targets three cancer types: advanced colorectal cancer, gastric cancer, and intestinal neuroendocrine tumours. Phase 1 is expected to enrol up to 15 patients across the three dose levels, leading to dose selection and expansion with indication-specific Phase 2 cohorts. The trial was initiated in 2024.
- Phase 1 dose escalation (Dose Levels 1-3), currently completing
- Recommended Phase 2 dose selection
- Indication-specific Phase 2 cohorts (colorectal, gastric, NETs)
For investors, the clear clinical pathway with defined patient numbers and expansion strategy provides visibility on development timelines. The multi-indication approach broadens commercial opportunity by addressing multiple gastrointestinal cancer types with a single therapeutic asset.
Chimeric’s broader cell therapy pipeline
CHM CDH17 sits within Chimeric’s diversified portfolio of four clinical-stage programmes spanning CAR-T and NK cell therapies. The therapy originated from research at the University of Pennsylvania, where preclinical evidence published in Nature Cancer in March 2022 demonstrated complete tumour eradication in seven cancer types in mice.
- CHM CDH17: First-in-class CDH17 CAR-T for gastrointestinal cancers (Phase 1/2)
- CHM CORE-NK: Allogeneic NK cell platform with Phase 1B combination trials underway
- CHM CLTX: CAR-T therapy for glioblastoma (Phase 1B)
For investors, multiple clinical-stage assets reduce single-programme risk whilst validating platform capabilities across both autologous and allogeneic approaches. The diversity of technology platforms and target indications provides multiple potential value inflection points.
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