Background/Objectives:

A multicenter Phase I study was designed to evaluate Nivolumab in combination with 3 different metronomic chemotherapy (MC) regimens in children with refractory /relapsing solid tumours or lymphoma. Objectives were to identify the MC regimen deemed feasible when given in combination with Nivolumab, to evaluate the safety profile, Overall Survival (OS), and Progression-Free Survival (PFS).

Methods:

Patients aged 6 -18 years were enrolled. Patients > 18 years could be included if diagnosed before 18. Patients received intravenous (IV) Nivolumab combined with oral cyclophosphamide and IV vinblastine (Arm A), oral 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 28-day cycles. Patients were evaluable if they received > 2 cycles and > 70% of the planned dose.

Results:

Sixteen patients were enrolled between March 2019 and September 2020, 3 in arm A, 6 in arm B, and 7 in arm C. Median age was 11.5 years (5-19). Median time between diagnosis and study entry was 32 months (6.5-117.5). Patients previously received a median of 3.5 (1-4) lines of systemic treatment, surgery (87.5%) and/or radiotherapy (69%). Median number of cycles was 2 (1-11). Median treatment duration was 56.5 days (28-342). Three patients were not evaluable (early tumor progression). No DLT was observed whatever the treatment arm. Grade 3 adverse events (AE) and Serious AE were observed in 43.8% and 12.5% respectively over the first 2 cycles. No grade 4 occurred. With a median follow-up of 7.3 months, 3-months PFS and OS were 35% and 74% respectively, in the whole population.

Conclusion:

Combinating Nivolumab with cyclophosphamide, vinblastine and capecitabine (Arm C) is safe. Randomised phase II trial comparing Arm C +/- Nivolumab is ongoing.