METRO-PD1: Phase 1 study of nivolumab in combination with metronomic chemotherapy in children and adolescents with relapsing/refractory solid tumors.
Immune checkpoint inhibitors
Immunotherapy
Metronomic chemotherapy
Pediatric cancer
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
06 Jan 2024
06 Jan 2024
Historique:
received:
26
09
2023
revised:
23
12
2023
accepted:
02
01
2024
medline:
11
1
2024
pubmed:
11
1
2024
entrez:
10
1
2024
Statut:
aheadofprint
Résumé
This multicenter Phase I study (NCT03585465) evaluated nivolumab in combination with 3 metronomic chemotherapy (MC) regimens in children with refractory/relapsing solid tumors. 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. 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.
Sections du résumé
BACKGROUND
BACKGROUND
This multicenter Phase I study (NCT03585465) evaluated nivolumab in combination with 3 metronomic chemotherapy (MC) regimens in children with refractory/relapsing solid tumors.
OBJECTIVES
OBJECTIVE
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.
POPULATION
METHODS
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.
RESULTS
RESULTS
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.
CONCLUSION
CONCLUSIONS
Arm C appears safe. A randomized phase II trial evaluating the addition of nivolumab to the triple MC is ongoing.
Identifiants
pubmed: 38199147
pii: S0959-8049(24)00001-7
doi: 10.1016/j.ejca.2024.113525
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
113525Informations de copyright
Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest Nivolumab and funding has been provided by BMS. NA has had an advisory role for Bayer and Partners Therapeutics and receives grants (institution) from Bristol Myers Squibb and drugs for a trial from Bristol Myers Squibb, Pierre Fabre, Merck, Pfizer, travel support from Roche; Speaker's Honoraria for Alection, he further has IDMC roles for Accord Healthcare. IA receives speaker’s honoraria from Alection. BG has had an advisory role for AstraZeneca and IDMC roles for trials sponsored by Roche and Novartis. Speaker's Honoraria - Bayer. PC speaker’s honoraria from Alection. NEW receives drug for a trial from Novartis, speaker’s honoraria from Alection, Eusapharma & Novartis. PL receives drug from BMS for a trial and speaker’s honoraria from Alection. MCLD, CL, AP, LW, CFC, GRV, VM and AB declare no conflict of interest.