Create Medicines, a Cambridge, Massachusetts-based biotech, dosed the first patient in a Phase I/II study of MT-304, an mRNA-LNP-delivered in vivo CAR therapy designed to program NK and myeloid cells against HER2-positive breast cancer and other HER2-positive solid tumors, including gastric cancer, the company announced April 23, 2026.
MT-304 is an NKp44-CAR construct delivered via a redosable mRNA-LNP system, with DAP12-mediated signaling intended to drive NK-mediated tumor lysis and myeloid-driven tumor remodeling simultaneously. The company said the therapy requires no lymphodepletion or ex vivo manufacturing, distinguishing it from conventional adoptive cell approaches. Preclinical data presented at AACR the preceding weekend showed tumor regression in models refractory to CAR T cells and checkpoint inhibitors, though no clinical pharmacodynamic or antitumor activity data in patients have been disclosed at this stage.
The Phase I/II study (NCT07334119) is a multi-center, open-label, dose-escalation trial enrolling adults with HER2-positive breast cancer and HER2-positive solid tumors. Primary objectives include safety, tolerability, pharmacokinetics, pharmacodynamics, CAR expression kinetics, and preliminary antitumor activity, with data intended to inform recommended Phase II dose selection. Enrollment size was not disclosed, and specific dose levels have not been stated. The trial is being conducted at Calvary Mater Newcastle in New South Wales, Australia, among other sites, with Dr. Jordan Cohen serving as principal investigator.
MT-304 enters a HER2-directed landscape in which trastuzumab deruxtecan has set a broad cross-tumor benchmark, reporting an objective response rate of 37.1% in the DESTINY-PanTumor02 study (NCT04482309) across HER2-expressing metastatic solid tumors. Tucatinib combined with trastuzumab produced an ORR of 41.9% in the MOUNTAINEER trial (NCT04579380), though that result is anchored primarily to HER2-positive metastatic colorectal cancer. Cross-trial comparisons are limited by differences in study design, duration, and patient populations, and MT-304's in vivo immune-programming approach has not yet generated clinical response data against which any comparison could be drawn.
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