CDH17 Remains a Promising Target, Even as the CHM CDH17 Trial Changes Course
The CHM CDH17 clinical trial, a CAR T-cell therapy built on research NETRF helped fund, is for people with certain gastrointestinal cancers, including well-differentiated intestinal neuroendocrine tumors (NETs). The therapy targets a protein called Cadherin 17, or CDH17, which is found on the surface of many neuroendocrine and other GI tumor cells.
Chimeric Therapeutics has now stopped enrollment and dosing in the Phase 1 trial after side effects were observed at the highest dose level. The company will not continue developing this version of the CAR T-cell therapy but believes CDH17 remains a valid target and plans to pursue a new in vivo approach.
The path from a laboratory discovery to a treatment for patients is rarely a straight line. Here, we explain what has changed, what hasn’t, and what this means for the neuroendocrine cancer community.
How NETRF’s Funding Led Here
The idea behind CHM CDH17 traces back to research NETRF supported in the lab of Xianxin Hua, MD, PhD, at the University of Pennsylvania. NETRF’s investment began with a grant in 2014 and continued with a 2018 Petersen Accelerator Award, helping to lay the foundation for a CAR T-cell therapy targeting CDH17. Chimeric Therapeutics later built on this foundational work to develop the CHM CDH17 CAR T-cell therapy and move it into clinical testing.
What Happened in the Trial
CHM CDH17 was being tested in the Phase 1 portion of a Phase 1/2 study using a standard dose- escalation design, a common and carefully controlled way to find a safe dose of a new therapy. After a second patient treated at Dose Level 3 experienced non-fatal dose-limiting side effects, the study’s independent Safety Monitoring Committee determined it was not safe to continue with this dose level. In keeping with the study’s protocol, enrollment and dosing have stopped. Patients already on the study will continue to be monitored and followed.
CDH17 Still Looks Like a Valid Target
This is the key takeaway for our community. The trial observed some anti-tumor activity, which is
meaningful evidence that CDH17 is a valid target for future treatments. However, the higher dose levels needed to achieve anti-tumor activity with this particular CAR T-cell product were not well tolerated by patients. Because of this, Chimeric will not continue developing CHM CDH17 in its current form.
What’s Next
Chimeric is now advancing a different approach: an in vivo delivery method for a CDH17-directed CAR T-cell therapy. Rather than modifying a patient’s T cells outside the body, as in the current trial, this method would potentially reprogram cells directly inside the body to target the cancer. Chimeric expects this approach to be faster and less costly to bring through early development. The in vivo program is still in the preclinical stage and requires more development before it could move into clinical testing.
What This Means for the Neuroendocrine Cancer Community
Setbacks like this one are a common part of drug development, and they don’t erase the progress made. CDH17 remains a scientifically validated target, one that traces directly back to research NETRF helped fund more than a decade ago. We’ll continue to follow this program and share updates as Chimeric’s CDH17-targeted research moves forward.
With Gratitude to Patients and Families
As Chimeric’s Non-Executive Chairman Bradley Glover noted in the announcement, “My first thoughts are with the patients who participated in this trial and with the clinicians and families who supported them.” We share that gratitude. NETRF is deeply thankful to the patients who participated in this study, as well as those who were screened or considered participating, and to their families and care teams. Their willingness to participate in clinical research helps advance knowledge and inform the development of better treatments for the neuroendocrine cancer community.
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Browse the NETRF Year in Research to learn more about recent, NETRF-funded research.