On February 14, 2026, Alphamab Oncology reported that the first patient was dosed in JSKN003-005, a Phase III study in HER2-positive advanced colorectal cancer (CRC). The investigational drug is JSKN003, described by the company as a biparatopic HER2 antibody–drug conjugate (ADC).
The event is an operational milestone that typically signals trial activation is complete at initial sites (e.g., approvals in place, drug supply released, and screening converting to dosing), moving the program from setup into patient accrual.
The company described JSKN003-005 as a randomized, open-label, controlled, multicenter Phase III trial comparing:
- JSKN003 (experimental arm)
vs - Investigator’s choice of later-line therapies: regorafenib, fruquintinib, or trifluridine–tipiracil(control arm)
The stated primary endpoint is progression-free survival (PFS) assessed by blinded independent central review (BICR) using RECIST v1.1.
This design aligns with common registration pathways in refractory/metastatic CRC: a randomized comparison to established later-line standards, with PFS-by-BICR used to reduce assessment bias in an open-label setting.
HER2-positive CRC represents a defined molecular subset where targeted therapy is clinically relevant, particularly after standard chemotherapy and biologics. In advanced CRC, later-line comparators such as regorafenib, fruquintinib, and trifluridine–tipiracil are widely used options, but their median PFS is generally measured in months, and objective responses are typically limited—creating a rationale to evaluate more active HER2-directed approaches in the biomarker-selected setting.
Alphamab Oncology cited a prior dataset presented at ESMO 2025: in 32 patients with HER2-positive advanced CRC, JSKN003 achieved an objective response rate (ORR) of 68.8% and median PFS of 11.04 months (company-reported). If replicated prospectively in a controlled Phase III trial against later-line therapies, outcomes of that magnitude would be clinically meaningful in this population because they would imply substantially higher response rates and longer disease control than typically expected from standard later-line regimens.
A Phase III CRC study is also a practical inflection point for manufacturing, pharmacovigilance scale-up, and global development planning. The choice of endpoints (PFS by BICR, RECIST v1.1) and a control arm reflecting physician-selected standards is consistent with evidence expectations for potential regulatory submissions in this setting.
You can read more about Alphamab Oncology’s Approval for JSKN033 Clinical Trial on OncoDaily.