A Phase I, First‐In‐Human Study of CBA‐1205, an Anti‐DLK1 Monoclonal Antibody, in Patients With Advanced Solid Tumors

ABSTRACT

CBA‐1205 is a novel humanized antibody targeting delta‐like 1 homolog (DLK1) that enhances antibody‐dependent cellular cytotoxicity activity. DLK1 overexpression has been reported in various cancer types, such as hepatocellular carcinoma and neuroblastoma. CBA‐1205 demonstrates potent antitumor activity in multiple tumor models, making it a potential treatment option for DLK1‐expressing cancers. This first‐in‐human, open‐label Phase I study includes three parts. Part 1, the dose‐escalation phase, primarily evaluates the safety profile, tolerability, and maximum tolerated dose of CBA‐1205. The drug is administered intravenously every 2 weeks in a 28‐day cycle. A standard 3 + 3 dose‐escalation design was used across seven cohorts. In a cohort of 22 Japanese patients, over 80% had undergone three or more prior treatments. CBA‐1205 was well tolerated, with no dose‐limiting toxicity observed at doses ranging from 0.1 to 30 mg/kg, the planned highest dose. There were no treatment‐related serious adverse events or trial‐related deaths. CBA‐1205 exposure, as measured by C_max, AUC_0–14, and AUC_0–∞, increased in a dose‐dependent manner. No serum anti‐CBA‐1205 antibodies were detected. Serum DLK1 concentrations were found in 6 out of 22 patients. Stable disease for over 6 months was observed in six patients, with progression‐free survival ranging from 29 to 144 weeks. CBA‐1205 was well tolerated, showing no severe toxicity in patients with advanced or recurrent solid tumors. The favorable safety profile and indications of potential activity support further investigation in Parts 2 and 3 of this Phase I study to evaluate the safety, tolerability, and preliminary efficacy of CBA‐1205.