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.
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).
Bidaux As & Garin G; Centre Léon Bérard; DRCI Promotion Phase Précoce.
EudraCT: 2014-001692-32; NCT02977156.
Centre Léon Bérard DRCI Promotion/Essais Précoces.
Centre Léon Bérard & Transgene S.A.
All authors have declared no conflicts of interest.