Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session

425 - A phase I dose escalation trial evaluating the impact of an in situ immunization strategy with intra-tumoral injections of Pexa-Vec in combination with ipilimumab in advanced solid tumors with injectable lesions

Date

14 Dec 2018

Session

Poster Display session

Presenters

Aurelien Marabelle

Citation

Annals of Oncology (2018) 29 (suppl_10): x24-x38. 10.1093/annonc/mdy487

Authors

A. Marabelle1, L. Eberst2, C. Terret3, F. Pilleul4, C. Mastier4, A. Bouhamama4, L. Gilles-Afchain3, S. Laurent3, I. Delzano3, C. Reynaud3, C. Caux5, C. Caux5, G. Garin6, A. Bidaux6, D. Perol6, N. Stojkowitz7, M. Homerin7, H. Leenders7, P. Cassier3

Author affiliations

  • 1 Drug Development Department, Gustave Roussy, 94805 - Villejuif/FR
  • 2 Medical Oncology, Centre Léon Bérard, 69373 - Lyon/FR
  • 3 Medical Oncology, Centre Léon Bérard, 69008 - Lyon/FR
  • 4 Radiology Department, Centre Léon Bérard, 69008 - Lyon/FR
  • 5 Cancer Research Center Of Lyon, INSERM, Cancer Research Center of Lyon, Centre Léon Bérard, 69008 - Lyon/FR
  • 6 Clinical Research, Centre Léon Bérard, 69008 - Lyon/FR
  • 7 Oncology, TRANSGENE, Paris/FR
More

Resources

Abstract 425

Background

In situ immunization is a strategy where immunomodulatory products are injected into one tumor site in order to use the tumor as its own vaccine and to trigger a systemic anti-tumor immune response. The Pexa-Vec (JX-594, Transgene) is an oncolytic virus genetically modified to secrete GM-CSF. We formulate the hypothesis that IT treatment with this oncolytic virus could synergize with anti-CTLA4 therapy via oncolytic virus-induced tumor cell death & tumor-antigen release, GM-CSF-induced recruitment/maturation/activation of antigen presenting cells, and anti-CTLA4-induced Treg blockade/depletion and reversion of T effectors inhibition.

Trial design

ISI-JX is a multicentric, Phase I dose escalation trial followed by an extension part aiming to evaluate the safety, feasibility, and anti-tumor effects of an in situ immunization strategy with IT injections of ipilimumab with Pexa-Vec in adults patients (pts) with solid tumors. The trial is conducted in pts with at least one injectable lesion (≥2 and ≤8 cm) and one distant non-injected measurable target site. Pts are treated with an IT injection of Pexa-Vec alone (1 x 109pfu) at Week 1 (W1) Day 1 (D1) followed by 3 IT injections of Pexa-Vec (1 x 109pfu) + ipilimumab (4 dose levels: 2.5, 5, 7.5, 10 mg/injection) at W3 D1, W5 D1 and W9 D1. Primary endpoint for escalation part is the occurrence of Dose Limiting Toxicities (DLT) defined as the toxicities occurring during the DLT assessment window (the first 5 weeks) related to Pexa-Vec, Ipilimumab or both; and the objective response rate as per immune related Response Criteria after 3 months of treatment for extension part. Secondary endpoints include the disease control rate, duration of response, progression free survival and overall survival. The dose escalation part follows a classical 3 + 3 design with 3 to 6 pts at each DL depending of the number of DTL observed (maximum of 24 pts). In the extension part, according to on the first stage of a Gehan design, 12 patients per cohort (3) will be enrolled (maximum of 36 pts). Up to date, the dose escalation part is ongoing: 8 pts were enrolled (DL1 n = 3; DL2 n = 3; DL3 n = 2).

Editorial acknowledgement

Bidaux As & Garin G; Centre Léon Bérard; DRCI Promotion Phase Précoce.

Clinical trial identification

EudraCT: 2014-001692-32; NCT02977156.

Legal entity responsible for the study

Centre Léon Bérard DRCI Promotion/Essais Précoces.

Funding

Centre Léon Bérard & Transgene S.A.

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.