Randomized phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced soft-tissue sarcoma - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Hematology and Oncology Année : 2022

Randomized phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced soft-tissue sarcoma

Maud Toulmonde
  • Fonction : Auteur
Sophie Cousin
  • Fonction : Auteur
Michele Kind
  • Fonction : Auteur
Jean-Philippe Guegan
  • Fonction : Auteur
Alban Bessede
  • Fonction : Auteur
Francois Le Loarer
  • Fonction : Auteur
Raul Perret
  • Fonction : Auteur
Antoine Italiano
  • Fonction : Auteur

Résumé

JX-594 is an oncolytic vaccinia virus genetically modified to replicate selectively in tumor cells. Metronomic chemotherapy has shown preclinical synergy with oncolytic viruses. We report here the results of the METROMAJX which is a randomized phase II clinical trial investigating the combination of JX-594 combined with metronomic cyclophosphamide (arm 1) or metronomic cyclophosphamide (arm 2) in patients with advanced STS. A two-stage Simon design was used. JX-594 was administered intra-venously at the dose 1.109 every 2 weeks for the first 3 injections and then every 3 weeks. Cyclophosphamide was given orally at the dose of 50 mg BID 1 week on 1 week off. The primary endpoint was the 6-month non progression rate. 20 patients were included (arm 1:15, arm 2:5). The two most frequent toxicities were grade 1 fatigue and fever and grade 2 fatigue and grade 2 lymphopenia in arms 1 and 2, respectively. In arm 1, 12 patients were assessable for the efficacy analysis. None of them were progression-free at 6 months indicating that the first stage of the Simon's design was not satisfied. One patient out 4 assessable for efficacy was progression-free at 6 months in arm 2. High throughput analysis of sequential plasma samples revealed an upregulation of protein biomarkers reflecting immune induction such as CXCL10 and soluble CD8 antigen in arm 1. Systemic treatment with JX-594 is safe in patients with advanced STS. Further investigations are needed to improve immune response to oncolytic viruses and define their therapeutic potential in patients with STS.
Fichier principal
Vignette du fichier
BPH_JHO_2022_Toulmonde.pdf (1.62 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-04008638 , version 1 (28-02-2023)

Licence

Identifiants

Citer

Maud Toulmonde, Sophie Cousin, Michele Kind, Jean-Philippe Guegan, Alban Bessede, et al.. Randomized phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced soft-tissue sarcoma. Journal of Hematology and Oncology, 2022, 15 (1), pp.149. ⟨10.1186/s13045-022-01370-9⟩. ⟨hal-04008638⟩

Collections

U1219
7 Consultations
41 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More