22 februari 2024: Bron: Antikankerfonds België

Van het Anticancerfund België kregen we een persbericht over een hoopgevende fase I veiligheidsstudie, de Metro-PD1 studie. Deze studie test de veiligheid en verbetering van de effectiviteit van immuuntherapie met nivolumab plus metronomische chemo bij 1 chemokuur, 2 chemokuren en 3 chemokuren bij kinderen en volwassenen met een recidief of ziekteprogressie met vormen van kanker met solide tumoren.

Uit een deelstudie bij 16 deelnemende kinderen (leeftijd mediaan 11 jaar) met solide tumoren (neuroblastomen, osteosarcoma en retinoblastoma), die een metronomische chemo = een lage dosis van drie verschillende chemokuren, kregen naast immuuntherapie met nivolumab in een normale dosis dan verbeterde de effectiviteit van de immuuntherapie het beste. Er traden geen extra ernstige bijwerkingen op door de toegevoegde chemotherapie. In de deelstudie werd Nivolumab gecombineerd met cyclofosfamide en vinblastine (groep A), capecitabine (groep B) of cyclofosfamide, vinblastine en capecitabine (groep C).  

Resultaten vertaald uit het abstract:

Het mediane aantal cycli was 2 (1−24), de mediane behandelingsduur was 56 dagen (18−714). In groep C was het mediane aantal cycli 4 met een mediane behandelingsduur van 95 dagen. Er werd geen Dosisbeperkende toxiciteiten (DLT's) waargenomen. Graad 3 bijwerkingen (AE) en ernstige bijwerkingen werden waargenomen bij respectievelijk 8 patiënten (50%) en 1 patiënt (6%) tijdens de eerste 2 cycli. Er trad geen graad 4 AE op.
De 6-maandelijkse PFS en OS bedroegen respectievelijk 12% en 44% in de gehele populatie. Langdurige stabiele ziekte werd waargenomen bij een hooggradig glioom en een atypische teratoïde rhabdoïde tumor.

Inmiddels is een fase II studie gestart.

Het volledige studieverslag is in PDF vorm in te zien en te downloaden. Klik op de titel van het abstract:

CLINICAL TRIAL| VOLUME 198113525FEBRUARY 2024
METRO-PD1: Phase 1 study of nivolumab in combination with metronomic chemotherapy in children and adolescents with relapsing/refractory solid tumors

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

Open AccessPublished:January 06, 2024DOI:https://doi.org/10.1016/j.ejca.2024.113525
  • 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.

Abstract

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: 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

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

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

Arm C appears safe. A randomized phase II trial evaluating the addition of nivolumab to the triple MC is ongoing.

CRediT authorship contribution statement

Conceptualization, NA and PL; methodology, NA, PL and MCLD.; validation, N.A., P.L. and MCLD; formal analysis, NA, PL, CL, MCLD and RT; investigation, NA, LM, IA, CFC, GRR, VM, BG, PC, NEW, PL.; resources, NA. PL and AP.; data curation, NA PL CL AP RT and MCLD; writing—original draft preparation, N.A. P.L MCLD; writing—review and editing, all authors; supervision, N.A. PL; project administration NA PL and AP. All authors have read and agreed to the submitted version of the manuscript.

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.

Acknowledgments

We thank all patients and their family for participating in this trial and clinicians involved in the care of the patients. BMS provided nivolumab free of charge and funding. Bristol Myers Squibb has reviewed the publication, however views and opinions described in this publication do not necessarily reflect those of Bristol Myers Squibb. We would like to thank the SFCE, Fondation Flavien, the Anticancer Fund, KiCa Fund managed by the King Baudouin Foundation, KickCancer, Alexine Clarysse Fund for funding the trial.

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Figures

  • Fig. 1
    Fig. 1Flow-chart of the study.
  • Fig. 2
    Fig. 2Kaplan-Meier curves for overall survival (OS) and progression-free survival (PFS) of all patients (a, N = 16) and patients included in arm C (b, N = 7).

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