PTCV Plus pIL-12 and Pembrolizumab Demonstrates Promising Responses in Unresectable/Metastatic HCC

Topline results from the phase 1b/2a GT-30 trial (NCT04251117) highlighted a positive safety profile and promising responses following the use of personalized therapeutic cancer vaccine (PTCV), GNOS-PV02, with plasmid-encoded IL-12 (pIL-12) and pembrolizumab (Keytruda) in patients with unresectable or metastatic hepatocellular carcinoma (HCC) who progressed on or are intolerant to first-line tyrosine kinase inhibitors, according to a press release from Geneos Therapeutics.

Based on RECIST v1.1 criteria, investigators reported an overall response rate (ORR) of 29.2% in the modified intent-to-treat (mITT) population, including 2 complete responses (CRs). Additionally, the disease control rate (DCR) was 54.2% (n = 13/24), which included 2 CRs, 5 partial responses, 6 instances of stable disease, and 10 instances of progressive disease. A third patient was determined to be cancer-free after a liver primary lesion and 2 lung metastases reduced in size, becoming fully responsive to surgery and radiation therapy. Moreover, investigators identified new and expended T-cell clones with a mostly CD8-positive activate phenotype in all evaluated patients in a pre-/post-vaccination analysis of T-cell receptors in blood and tumor tissue. These clones potentially mediated observed tumor regressions after being trafficked to the tumor microenvironment by week 9 of treatment.

The study regimen did not yield any dose limiting toxicities, and there were no grade 3 or 4 serious adverse effects (SAEs) related to PTCV and pIL-12 treatment. Grade 1 and 2 AEs related to PTCV and pIL-12 treatment were transient and mild. One patient was deemed unevaluable but was included in the mITT analysis after discontinuing treatment due to a non–treatment-related SAE.

“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,” Edward Gane, MD, FAASLD, professor of medicine at the University of Auckland, New Zealand and chief hepatologist, transplant physician, and deputy director of the New Zealand Liver Transplant Unit at Auckland City Hospital, said in the press release. “To see 3 cancer-free patients out of 23 evaluable in second-line advanced HCC, with a 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.”

Data from the GT-30 trial will be presented on November 10 in an oral presentation at the Society for Immunotherapy of Cancer 37th Annual Meeting. Additionally, trial investigators plan to enroll a further 12 patients and give first reports on benchmark overall survival (OS) from the full cohort of 36 in mid-2023.

Among the 24 patients with HCC who were first to enroll on the single-arm, open-label trial, 23 had evaluable results. Treatment consisted of DNA plasmid-encoded PTCV with T-cell–stimulating cytokine pIL-12 via intradermal injection and electroporation followed by intravenous infusion of pembrolizumab.

Primary end points of the GT-30 trial included AEs based on CTCAE v5.0 and the immunogenicity of PTCV as measured by interferon-γ secreting T lymphocytes in peripheral blood mononuclear cells (PMBCs) and by T-cell activation and cytolytic cell phenotype in PMBCs. Secondary end points included antitumor activity as measured by ORR, DCR, duration of response, progression-free survival, and OS.

Patients 18 years and older who had a histologically or cytologically confirmed diagnosis of HCC based on pathology reports were eligible to enroll on the study. Additional inclusion criteria included having Barcelona Clinic Liver Cancer stage C or B disease, a Child-Pugh class A liver score, a predicted life expectancy of more than 6 months, measurable disease per RECIST v1.1 criteria, and an ECOG performance status of 0 or 1 within 7 days of first dose of the study treatment.

Reference

Geneos Therapeutics announces positive clinical data for personalized therapeutic cancer vaccines in ongoing liver cancer trial. News release. Geneos Therapeutics. November 7, 2022. Accessed November 8, 2022. https://prn.to/3FX44wH