A Phase 1 trial assessing a combination of the immune checkpoint inhibitor Yervoy (ipilimumab) and Transgene’s oncolytic virus Pexa-Vec as a treatment for multiple advanced solid tumors has dosed its first patient at the Léon Bérard Cancer Center in Lyon, France.
The study will enroll up to 60 patients in multiple clinical centers in France. Patients will receive both treatments simultaneously injected into their tumors.
“We believe in the synergistic potential of the combination between oncolytic viruses and immune checkpoint-targeted antibodies,” Dr. Aurélien Marabelle, MD, PhD, from Gustave Roussy, said in a news release. Marabelle is a world expert in immunotherapy clinical research and coordinating investigator of the study.
“We believe that the intra-tumoral co-delivery of these immunotherapies will trigger a better priming of the anti-tumor immune response while avoiding off-target toxicities,” Marabelle added. “We hope this novel ‘in situ immunization’ strategy will overcome the resistance to cancer immunotherapy that we observe in many patients.”
Pexa-Vec, derived from the term pexastimogene devacirepvec, is an oncolytic virus designed to kill cancer cells using three mechanisms. It triggers the breakdown of cancer cells through viral replication. It promotes disruption of blood vessels, reducing the tumor’s blood supply. And the GM-CSF gene it contains attracts immune cells to tumors and stimulates strong anti-tumoral responses.
The therapy has shown promising activity and safety in Phase 2 trials of its use as a first-line therapy for liver cancer patients.
Transgene is now assessing the safety and effectiveness of Pexa-Vec combined with the immune checkpoint inhibitor Yervoy in patients with other solid tumors.
The investigator-initited ISI-JX study (NCT02977156) is an open-label, single-arm, dose-escalation Phase 1 trial that will be conducted in two parts.
Part A is designed to find the optimal doses and dosing regimen of Pexa-Vec and Yervoy. It will include three to six patients with advanced or metastatic solid cancer — except liver cancer.
Part B is designed to assess the safety and effectiveness of the optimal dosing schedule found in Part A. It will enroll patients with melanoma, colorectal cancer, gastric cancer, head and neck cancer, triple negative breast cancer, and mesothelioma.
The primary measure for assessing Part B results is an objective response rate at three months of follow-up. An objective response is a full or partial response. Secondary Part B measures include disease control rate, duration of response to treatment, progression-free patient survival, and overall survival.
“This trial aims to first demonstrate that the regimen of our oncolytic virus Pexa-Vec plus ipilimumab is well tolerated. We expect that the intra-tumoral administration of ipilimumab will have less systemic toxicity thanks to its local administration,” said Maud Brandely, chief medical officer of Transgene. “Another objective is to show the antitumor activity of the regimen in patients with advanced solid tumors which have exhausted all standard therapeutic options.”