This example phase 1/2, open-label, biomarker-selected study evaluates EB-HC01, an allogeneic dual-target CARNK product composed of a 1:1 mixture of HER2-CAR-NK and CEACAM5-CAR-NK cells, in adults with unresectable or metastatic cholangiocarcinoma or other biliary tract cancers after standard therapy. Part A determines safety, dose-limiting toxicities (DLTs), and the recommended phase 2 dose (RP2D) after reduced-intensity lymphodepletion. Part B evaluates preliminary anti-tumor activity, CAR-NK persistence, and biomarker-response associations.
Histologically or cytologically confirmed unresectable, recurrent, or metastatic intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder carcinoma.
Disease progression after at least 1 prior gemcitabine/platinum-containing regimen in the advanced setting; prior durvalumab and prior HER2-targeted therapy are allowed.
Central biomarker confirmation of HER2 positivity (IHC 3+ or IHC 2+/ISH+ or ERBB2 amplification) and CEACAM5/CEA positivity (membranous expression in >=20% of viable tumor cells by IHC).
At least 1 measurable lesion according to RECIST 1.1.
Prior HER2-directed or CEA-directed gene-modified cell therapy.
Untreated or unstable CNS metastases or leptomeningeal disease.
Active uncontrolled infection, including uncontrolled cholangitis, sepsis, or clinically significant uncontrolled hepatitis or HIV infection.
Ongoing systemic immunosuppression greater than 10 mg/day prednisone equivalent within 7 days before lymphodepletion.