Transgene testing Opdivo with Pexa-Vec to treat HCC – first patient treated

Transgene has treated the first patient in a Phase 1/2 clinical trial for the combination of Pexa-Vec with Opdivo as a first-line treatment of advanced hepatocellular carcinoma (HCC). The trial will assess the safety and tolerability as well as the anti-tumor activity and efficacy of this immunotherapy combination regimen in up to 36 patients (NCT03071094).  This tumour accounts for approximately 75% of liver cancers. 

In a Phase 2 trial of Pexa-Vec in first-line HCC, overall survival was improved in a dose dependent manner. The median overall survival was 14.1 months for the high-dose group compared to 6.7 months for the low-dose group.

Pexa-Vec’s mechanism of action and its safety profile make it an appropriate candidate for use in combination with immune checkpoint inhibitors (ICIs) such as nivolumab.

Nivolumab (Opdivo®, Bristol-Myers Squibb) is a monoclonal antibody targeted against the PD-1 receptor. It is approved in several cancer indications and is currently being investigated in HCC within a global Phase 3 trial.

By targeting two distinct steps in the immune response against cancer cells, the combination of Pexa-Vec and nivolumab has the potential to be significantly more effective than either product alone. There is a strong scientific rationale that suggests that Pexa-Vec’s anti-cancer effects could be enhanced by combining it with nivolumab, which suppresses the cancer cells’ ability to escape the body’s immune response.

Commenting on this innovative clinical trial, Prof Olivier Rosmorduc, MD, head of Hepato-gastroenterology department at La Pitié-Salpêtrière Hospital in Paris and principal investigator of the trial, said that improving the treatment of HCC needs a therapeutic approach capable of significantly boosting the immune system. He said he was confident that combining immunotherapies with local and systemic effects such as anti-PD1 nivolumab and the oncolytic virus Pexa-Vec is a powerful strategy to better treat patients with advanced hepatocellular carcinoma.

Maud Brandely, Chief Medical Officer of Transgene, said: “HCC has a dismal prognosis which has been marginally improved by current therapeutic options. Preclinical and clinical data generated respectively with Pexa-Vec and nivolumab suggest that, in combination, these novel immunotherapies, with their complimentary modes of action, have the potential to be more active than each single agent alone. This may translate into better response rate and increased overall survival in HCC patients.”