Pexa-Vec Combo Unlikely to Benefit Advanced Liver Cancer Patients in Phase 3 Trial, Monitoring Group Says

Adding the cancer vaccine Pexa-Vec to Nexavar (sorafenib), a standard of care, is not likely to improve overall survival of patients with advanced liver cancer, an interim analysis by the independent data monitoring committee of the PHOCUS Phase 3 trial reported.

Based on these findings, the committee is recommending a stop to patient enrollment in the study, as its main goal of better overall survival is unlikely to be reached. No safety concerns were found, Transgene, the vaccine’s developer, announced.

Pexa-Vec, whose name is derived from pexastimogene devacirepvec, is an oncolytic virus designed to kill cancer cells in three ways, Transgene states. The vaccine triggers the breakdown of cancer cells through viral replication, and promotes disruption of blood vessels so as to reduce a tumor’s blood supply. The GM-CSF gene it contains also attracts immune cells to cancer cells, stimulating stronger anti-tumor responses.

In a prior Phase 2 trial (NCT00554372) testing Pexa-Vec in advanced liver cancer patients, a high-dose of the treatment led to an overall survival of 14.1 months, which compared favorably to current treatments for liver cancer.

The vaccine’s mechanism of action and safety make it an appropriate candidate for combination treatments, which led researchers to test it with Nexavar in the global PHOCUS Phase 3 trial (NCT02562755).

PHOCUS was designed to compare a combination of Pexa-Vec plus Nexavar, versus Nexavar alone, in up to 600 advanced liver cancer patients who had not been given other systemic therapies.

Its main goal was to assess whether the combination increased overall survival, while secondary measures included overall response rate, time to disease progression or death, and safety, as measured by the number of adverse events reported.

However, a planned futility analysis — meant to determine if the trial will meet its goals at the final analysis — showed that PHOCUS is unlikely to meet its primary goal, leading the monitoring committee to recommend a halt to enrollment.

Transgene plans to provide more information in an upcoming conference call.

Other trials testing this cancer vaccine in combination with immune checkpoint inhibitors will not be affected by this decision, the company said. These include a Phase 1/2 trial (NCT03071094) testing Pexa-Vec plus the PD-1 inhibitor Opdivo (nivolumab) in advanced liver cancer, and trials for metastatic solid tumors (NCT02977156), colorectal cancer (NCT03206073), and kidney cancer (NCT03294083).

All these ongoing trials are still recruiting. For more information, click on their identifying NCT numbers.