PTCV Plus pIL-12 and Pembrolizumab demonstrate promising responses in unresectable/metastatic HCC

A treatment regimen consisting of a personalized therapeutic cancer vaccine, GNOS-PV02, along with plasmid-encoded IL-12 and pembrolizumab resulted in an overall response rate of 20.9% in evaluable patients with unresectable or metastatic hepatocellular carcinoma.

Topline results from the Phase 1b/2a GT-30 trial (NCT04251117) demonstrated a positive safety profile and promising responses following the use of the 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 have progressed 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 (CR). Moreover, the disease control rate (DCR) was 54.2% (n=13/24), which included 2 CR, 5 partial responses, 6 cases of stable disease and 10 cases of progressive disease. A third patient was determined to be cancer-free after primary liver injury and 2 lung metastases of reduced size, becoming fully responsive to surgery and radiotherapy. Additionally, researchers identified new and depleted T cell clones with an activated predominantly CD8 positive phenotype in all patients assessed in a pre-/post-vaccination analysis of T cell receptors in blood and tumor tissues. These clones potentially induced tumor regressions observed after being transported to the tumor microenvironment at the ninth week of treatment.

The study treatment regimen did not result in any dose-limiting toxicities, and there were no grade 3 or 4 serious adverse reactions (SAEs) related to treatment with PTCV and pIL-12. Grade 1 and 2 AEs related to PTCV and pIL-12 treatment were transient and mild. One patient was deemed not evaluable but was included in the mITT analysis after treatment discontinuation due to an unrelated SAE.

“As a physician who has managed patients with advanced liver cancer for more than two decades, I am delighted with the response rate and immunological 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 Hospital , said in the press release. “Seeing 3 out of 23 cancer-free patients evaluable in advanced second-line HCC, with such well-tolerated treatment, tells me that personalized therapeutic cancer vaccination may finally be here to stay. If these response rates continue as the program progresses towards registration, then I see PTCV becoming an essential foundation of cancer immunotherapy, not just for HCC, but more broadly.

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

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

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

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

Reference

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

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