Personalized Therapeutic Cancer Vaccine Continues in Liver Cancer Clinical Trial

Geneos Therapeutics announced positive safety and efficacy data from the first 24 patients enrolled in GT-30. GT-30 is an ongoing single-arm open-label multi-center Phase 1b/2a study to evaluate safety, immunogenicity, and efficacy of PTCV (GNOS-PV02) administered in combination with plasmid-encoded IL-12 (pIL12) and pembrolizumab in patients with unresectable or metastatic hepatocellular carcinoma (HCC) who progress on, or are intolerant to, first-line tyrosine kinase inhibitors (sorafenib or lenvatinib).

By RECIST1.1 an overall response rate of 29.2 percent in the modified intent-to-treat analysis (mITT) was observed, including complete responses in two patients as well as a third cancer-free patient who achieved secondary resectability and four additional partial responses.

• To date, no dose-limiting toxicities nor PTCV + pIL12 related serious adverse events (SAEs) or Grade 3 or 4 adverse events (AEs) have been reported. Grade 1 and 2 PTCV + pIL12 related AEs have been transient and mild.
• By RECIST1.1, disease control rate is 54.2 percent (13/24; mITT) consisting of two complete responses (CR), five partial responses (PR), six stable disease (SD) and 10 progressive disease (PD).
• A third patient (deemed a radiological PR) is cancer-free after a liver primary lesion and two lung metastases all reduced in size to become fully responsive to surgery and radiation therapy.
• One patient discontinued treatment due to a non-treatment-related SAE and was deemed unevaluable but included in the mITT analysis.
• Novel and expanded T cell clones, predominantly CD8+ with activated phenotype, were identified in 100 percent of evaluated patients via pre-/post-vaccination analysis of T cell receptor (TCR) repertoire in peripheral blood and tumor tissue. These clones trafficked to the tumor microenvironment (TME) by week nine, potentially mediating the observed tumor regressions.

“As a physician who has been managing patients with advanced liver cancer for more than two decades, I am thrilled by the response rate and immunologic activity we are seeing with this promising form of therapeutic cancer vaccination,” stated Dr. Gane, professor of medicine at the University of Auckland, New Zealand, hepatologist and deputy director of the New Zealand Liver Unit at Auckland City Hospital, in a press release on November 7, 2022.

“To see three cancer-free patients out of 23 evaluable in second-line advanced HCC, with treatment this well tolerated, tells me that personalized therapeutic cancer vaccination may now, finally, be here to stay."

"If these response rates are maintained as the program advances toward registration, then I see PTCV becoming a core foundation of cancer immunotherapy, not just for HCC, but broadly.”