{Reference Type}: Clinical Trial, Phase I
{Title}: METRO-PD1: Phase 1 study of nivolumab in combination with metronomic chemotherapy in children and adolescents with relapsing/refractory solid tumors.
{Author}: André N;Deley MCL;Léguillette C;Probst A;Willems L;Travers R;Aerts I;Faure-Conter C;Revond-Riviere G;Min V;Geoerger B;Chastagner P;Entz-Werlé N;Leblond P;
{Journal}: Eur J Cancer
{Volume}: 198
{Issue}: 0
{Year}: 2024 Feb 6
{Factor}: 10.002
{DOI}: 10.1016/j.ejca.2024.113525
{Abstract}: <B>BACKGROUND: </B>This multicenter Phase I study (NCT03585465) evaluated nivolumab in combination with 3 metronomic chemotherapy (MC) regimens in children with refractory/relapsing solid tumors.<BR><B>OBJECTIVE: </B>To evaluate the feasibility and safety of the three regimens METHODS: Patients aged < 18 years were enrolled. Nivolumab was combined with cyclophosphamide and vinblastine (arm A), capecitabine (arm B), or cyclophosphamide, vinblastine and capecitabine (arm C). Arm A and B were allocated sequentially. Arm C opened only if A and B were deemed safe. Dose-limiting toxicities (DLTs) were evaluated over the first two cycles. Patients were evaluable if they received > 2 cycles and > 70% of the planned dose.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>Arm C appears safe. A randomized phase II trial evaluating the addition of nivolumab to the triple MC is ongoing.