414P - A phase Ib trial of JX-594 (Pexa-Vec), a targeted multimechanistic oncolytic vaccinia virus, in combination with low-dose cyclophosphamide in patie...

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Anti-Cancer Agents & Biologic Therapy
Drug Development
Cancer Immunology and Immunotherapy
Presenter Maud Toulmonde
Citation Annals of Oncology (2017) 28 (suppl_5): v122-v141. 10.1093/annonc/mdx367
Authors M. Toulmonde1, S. Cousin1, A. Bessede2, M. Homerin3, N. Stojkowitz4, M. Lusky5, M. Pulido6, A. Italiano1
  • 1Medical Oncology, Institute Bergonié, 33076 - Bordeaux/FR
  • 2Immusmol, Immusmol, 33000 - bordeaux/FR
  • 3Clinical Research, TRANSGENE SA, 67400 - Illkirch-Graffenstaden/FR
  • 4Clinical Research, Transgene SA, 67400 - Illkirch-Graffenstaden/FR
  • 5Project Management, Transgene SA, 67400 - Illkirch-Graffenstaden/FR
  • 6Biostatistics, Institute Bergonié, 33076 - Bordeaux/FR

Abstract

Background

JX-594 (Pexa-Vec) is a targeted oncolytic vaccinia virus designed to selectively replicate in and destroy cancer cells with epidermal growth factor receptor (EGFR)/ras pathway activation. Direct oncolysis plus GM-CSF expression is accompanied by tumor vascular disruption and anti-tumoral immunity. JX-594 was well-tolerated intravenously (IV) and intratumorally (IT). Given the immunomodulatory effects of low-dose cyclophosphamide (CP), anti-tumor synergy is predicted with JX-594.

Methods

CP was delivered orally at the dose of 50 mg BID one week on one week off. JX-594 was delivered IV at day 8 of each day 28-cycle. 2 dose levels of JX-594 were explored: 3.108 and 1.109 plaque forming units (pfu). The primary objective of the study was to determine the safety of JX-594 in combination with low-dose CP in patients with advanced solid tumors. Secondary objectives include response rates, PFS, pharmacokinetics and pharmacodynamics.

Results

Ten patients entered the study. 9 were evaluable for safety. No dose limiting toxicity was observed. The combination regimen was well-tolerated. The most frequent adverse events were grade 1-2 fever/transient flu-like symptoms (n = 10), grade 1-2 nausea (n = 5), grade 1-2 anemia (n = 4) and grade 1-2 fatigue (n = 4). 2 patients (breast cancer, ovarian cancer) had stable disease as best overall response.

Conclusions

IV JX-594 was well-tolerated in combination with low-dose CP. PK and PD (immunological profiling) will be presented at the meeting. Two phase 2 studies are ongoing in patients with advanced HER2 negative breast cancer and advanced soft-tissue sarcomas, respectively.

Clinical trial identification

NCT02630368

Legal entity responsible for the study

Institut Bergonié

Funding

INCA

Disclosure

All authors have declared no conflicts of interest.