The first patient has been dosed in the Phase 2 portion of a clinical trial evaluating a combination of the cancer vaccine Pexa-Vec and chemotherapy in solid tumor patients.
The dosing at the Institut Bergonié in Bordeaux, France, marks the second stage of the METROmaJX Phase 1/2 trial (NCT02630368). It will evaluate a combination of Pexa-Vec, which is produced by Transgene, and metronomic cyclophosphamide in patients with advanced soft tissue sarcoma (STS) and HER2-negative breast cancer. The French National Cancer Institute INCa is backing the study.
“We are grateful to Institut Bergonié and INCa for supporting the METROmaJX trial,” Maud Brandely, chief medical officer of Transgene, said in a press release. “We hope that the Phase 2 part of the study will demonstrate that this novel oncolytic virus plus chemotherapy regimen can be synergistic, resulting in a high response rate which could translate into improved overall survival. Advanced breast cancer and soft tissue sarcoma are two diseases which clearly require better treatment options for the patients.”
Pexa-Vec, whose name is derived from pexastimogene devacirepvec, is an oncolytic virus designed to kill cancer cells in three ways. It triggers the breakdown of cancer cells through viral replication. It promotes disruption of blood vessels, reducing a tumor’s blood supply. And the GM-CSF gene it contains attracts immune cells to tumors, stimulating strong anti-tumor responses.
The vaccine’s mechanism of action and safety make it an appropriate candidate for combination treatments, Transgene said. The bottom line is that it can improve the anti-tumor effects of other immunomodulatory agents, the company added.
Cyclophosphamide is a chemotherapy that can modulate immune activity when administered in metronomic fashion — that is, in lots of low doses.
In the Phase 1 part of the METROmaJX study, researchers administered two dose levels of Pexa-Vec to determine the maximum that patients could tolerate. Then they gave the trial participants a combination of that Pexa-Vec dose and metronomic cyclophosphamide twice a day every other week.
Patients tolerated the combination well enough for the trial to progress to the Phase 2 stage. Transgene plans to present results of the Phase 1 stage at a medical conference.
Researchers will divide patients into three groups for the Phase 2 part of the trial. Forty-eight soft tissue sarcoma patients will receive Pexa-Vec plus metronomic cyclophosphamide. Twenty-four sarcoma patients will receive metronimic cyclophosphamide alone. And 32 breast cancer patients will receive the combo treatment.
The primary measurement of the combo’s effectiveness will be the proportion of patients who respond to the treatment or whose disease is stable at six months. Secondary endpoints include patients’ objective response rate; progression-free survival — or the number of patients whose disease has failed to progress — at one and two years; and overall patient survival rates. Objective response refers to the number of patients who respond fully or partially to a treatment.
“The METROmaJX trial has confirmed the good tolerability of intravenous administration of the oncolytic virus Pexa-Vec, when associated with low-dose cyclophosphamide,” said Dr. Antoine Italiano of the Institut Bergonié, the principal investigator of the study. “We hope this novel regimen will demonstrate its efficacy in the Phase 2 part of the trial.”