Work

Feasibility of Atezolizumab in Combination With Chemotherapy for Children With Relapsed or Refractory Solid Tumors

Year: 2025

Type: article

Abstract: ABSTRACT Background Combining immune checkpoint inhibitors (ICI) with chemotherapy may improve treatment response in children with solid tumors. We sought to determine the feasibility of combining vincristine, irinotecan, and temozolomide with the ICI atezolizumab in children with relapsed or refractory solid tumors (VITAS;). Methods Patients ≥6 months and ≤18 years old with a relapsed or refractory solid tumor, no prior ICI, and evaluable disease per RECIST v1.1 were eligible for the Phase I cohort (NCT04796012). Patients received atezolizumab 15 mg/kg on Day 1, vincristine 1.5 mg/m 2 on Day 1, irinotecan 50 mg/m 2 on Days 1–5, and temozolomide 100 mg/m 2 on Days 1–5 in 21‐day cycles. The primary endpoint was the number of patients with dose‐limiting toxicities (DLT) in the first two cycles of therapy. Results Six patients (median age: 14 years) with rhabdomyosarcoma ( n = 3), osteosarcoma ( n = 2), and Ewing sarcoma ( n = 1) received therapy and were evaluable for toxicity. Patients received a median of seven (range: 2–20) cycles of treatment. No patients experienced a DLT. One patient experienced Grade 2 immune‐related colitis. Four patients experienced Grade ≥3 adverse events (decreased neutrophil count, febrile neutropenia, weight loss, anorexia). One patient with rhabdomyosarcoma had a sustained partial response through 16 cycles. One patient with relapsed pulmonary osteosarcoma has ongoing stable disease through 20 cycles. Conclusions Atezolizumab combined with vincristine, irinotecan, and temozolomide was feasible and well tolerated in children with solid tumors. Efficacy of this regimen is now being assessed in relapsed and refractory rhabdomyosarcoma in an ongoing Phase II cohort.

Source: Pediatric Blood & Cancer

DOI: 10.1002/pbc.32046