METRO-PD1: Phase 1 study of nivolumab in combination with metronomic chemotherapy in children and adolescents with relapsing/refractory solid tumors

This multicenter Phase I study (NCT03585465) evaluated nivolumab in combination with 3 metronomic chemotherapy (MC) regimens in children with refractory/relapsing solid tumors. Objectives: To evaluate the feasibility and safety of the three regimens Patients aged 2 cycles and > 70% of the planned dose. Sixteen patients were enrolled, 3 in arm A, 6 in arm B, and 7 in arm C. Median age was 11.5 years (range, 5–19). Patients previously received a median of 3.5 (range, 1–4) lines of systemic treatment, 14 patients had surgery and 11 had radiotherapy. Median number of cycles was 2 (1−24), median treatment duration was 56 days (18−714). In arm C, median number of cycles was 4 with median treatment duration of 95 days. No DLT was observed. Grade 3 adverse events (AE) and serious AE were observed in 8 patients (50%) and 1 patient (6%), respectively, over the first 2 cycles. No grade 4 AE occurred. The 6-month PFS and OS were 12% and 44%, respectively, in the whole population. Prolonged stable disease was observed in a high-grade glioma and an atypical teratoid rhabdoid tumor. Arm C appears safe. A randomized phase II trial evaluating the addition of nivolumab to the triple MC is ongoing. •The safety of new metronomic regimen associated with nivolumab have been evaluated.•The combinations of metronomic regimens and nivolumab appear safe with no observed DLT.•Long term disease control has been observed in patients with high grade glioma and ATRT.•A randomized phase 2 trial is evaluating the addition of nivolumab to the metronomic regimen.