(P 271) SAFETY AND EFFICACY OF CABOZANTINIB IN PEDIATRIC PATIENTS WITH MALIGNANT SOLID TUMORS (CAMEL TRIAL/NCCH2106): A SINGLE-CENTRE PHASE I TRIAL

Objective: Cabozantinib (CABO) has been reported to be effective for osteosarcoma (OS) and Ewing sarcoma. In the United States, a phase I trial of CABO in pediatric patients (ADVL1211 study) established 40 mg/m2 as the recommended phase 2 dose (RP2D). However, safety data in Japanese pediatric patients were lacking; therefore, a phase I trial of CABO in Japanese children was conducted.

Methods: This open-label, single-center phase I trial evaluated the safety, efficacy, and RP2D of CABO in pediatric patients aged 3–19 years with relapsed or metastatic malignant solid tumors. CABO was administered orally once daily at a dose of 40 mg/m2. In cohort 1, the incidence of adverse events (AEs) equivalent to dose-limiting toxicity (DLT) was evaluated in six patients. Once the RP2D was confirmed, additional patients were enrolled in cohort 2. The primary endpoint was the incidence of DLTs in cohort 1. Secondary endpoints included the incidence of AEs, pharmacokinetic parameters, overall response, and the 16-week disease control rate.

Results: Between April 2022 and the data cut-off date in April 2024, 12 pediatric patients, including 5 with OS, were enrolled. Among the six patients in cohort 1, one patient experienced a grade 3 elevation of alanine aminotransferase during the first cycle, which was considered a DLT. Based on this, 40 mg/m2 was confirmed as the RP2D. No additional DLT-equivalent AEs were observed among the 12 patients. In the context of severe AEs, one patient died due to CABO-related upper gastrointestinal bleeding. Other common grade ≥3 CABO-related AEs were manageable hematologic toxicities. Noncompartmental analysis showed that the steady-state clearance (1.51 ± 1.34 L/h/m2) was consistent with previously reported data. In terms of efficacy, the 16-week disease control rate was 50.0% (3/6). Stable disease was achieved in 66.7% (2/3) of patients with OS, one of whom maintained long-term disease control for >1 year.

Conclusion: In this study, CABO at 40 mg/m2/day was tolerable in Japanese pediatric patients. The incidence of DLTs at this dose was lower compared to the ADVL1211 study. Although the number of enrolled patients was small, these findings suggest that CABO may be effective in Japanese pediatric patients with OS, consistent with results from overseas studies.

Funding: This study was supported by Takeda Pharmaceutical Co., Ltd.
Clinical Trial Registration: jRCT2031210610