Interim analysis of CaboMain: A prospective, single-arm phase 2 clinical trial of cabozantinib as maintenance therapy for patients with “ultra-high-risk” pediatric solid tumors.

Abstract

10014 Background: There are patients with pediatric solid tumors, including those with relapsed/refractory disease, with “ultra-high” risk (UHR) disease (1-year progression free survival (1-yr PFS) <25%) even when achieving disease control. Most pediatric solid tumors do not have a therapeutically-targetable oncogenic driver, limiting treatment options for maintenance therapy. Cabozantinib is a multitargeted tyrosine kinase inhibitor with demonstrated activity against many solid tumors, with a defined safety profile and dosing in pediatric and young adult patients. We hypothesize that use of cabozantinib for 1 year, after achieving disease control, can improve 1-yr PFS to ≥ 45%. Methods: We are performing a multisite, open-label, single-arm Phase 2 clinical trial for patients with pediatric solid tumors with 4 strata; Stratum A, primary stratum for analysis, enrolls patients with UHR disease. Patients must have completed prior therapy at least 4 weeks and no longer than 12 weeks before enrollment with stable disease or better at time of enrollment. Enrolled patients receive cabozantinib as per dosing nomogram at 40 mg/m 2 /day, taken for up to 365 days from start of therapy. Primary outcome is 1-yr PFS, with Bayesian time-to-event optimal phase 2 design for analysis. Interim analysis follows the rules: assuming a Beta (0.25,0.75) prior distribution for efficacy and 88% statistical power, at interim at least 5/18 evaluable patients must have achieved 1-yr PFS to justify ongoing enrollment. Interim analysis reporting has been recommended by the Data Safety and Monitoring Committee. Results: We report the interim results as of 11/1/2025, which includes all enrolled patients on Stratum A who have reached 1 year after start of therapy (n=13). Eight of thirteen patients reached 1-yr PFS; by diagnosis, neuroblastoma (NBL) = 2, Ewing sarcoma (EWS)= 3, osteosarcoma (OST)= 3. Of those not reaching the one-year time point, 2 patients progressed after voluntarily discontinuing cabozantinib (1 NBL, 1 month after discontinuation; 1 OST, 5 months after discontinuation), 1 NBL elected radiation therapy and was removed from study, and 2 OST progressed on study treatment. Having reached the interim analysis benchmark, enrollment continues. Three additional strata (metastatic EWS, metastatic OST, and fusion-positive metastatic rhabdomyosarcoma, each at end of 1 st line therapy) also continue to enroll, as secondary endpoints. Longer-term PFS and overall survival, patient reported outcomes, and exploratory biological measures continue to be tabulated for later analysis. Conclusions: Use of cabozantinib as maintenance therapy, after prior treatment and achievement of stable disease or better response, has been determined to be feasible to demonstrate improvement of 1-yr PFS by at least 20%, and ongoing enrollment is justified. Clinical trial information: NCT05135975 .