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

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.