Positive Early-Phase Results for Geneos' Personalized Cancer Vaccine Trial

Geneos Therapeutics, a clinical-stage biotherapeutics firm, has reported positive results from its GT-30 clinical trial, which focuses on personalized therapeutic cancer vaccines (PTCVs). The trial's data, published in Nature Medicine, indicate that the treatment has achieved its primary goals of safety and immunogenicity, along with a secondary goal of efficacy, based on the observed response rate.

The study, which involved 36 patients, was a Phase 1/2 single-arm, open-label, multi-center trial of GNOS-PV02, a PTCV encoded with DNA plasmid, combined with IL-12, a cytokine adjuvant, and pembrolizumab, a PD-1 inhibitor. This treatment was given to second-line patients with advanced hepatocellular carcinoma (HCC) who had previously received a multi-tyrosine kinase inhibitor. The adverse events related to the PTCV were mild, limited to Grades 1 and 2, with the most common being injection site reactions in 41.6% of the patients.

The objective response rate (ORR) for the GT-30 trial stands at 30.6%, which includes three complete responses and eight partial responses. This rate is statistically significant when compared to the historical control of 16.9% for pembrolizumab monotherapy. The complete response rate for GT-30 is 8.3%, which is higher than the historical rate for anti-PD-1 monotherapy in second-line advanced HCC. The median overall survival (mOS) for the GT-30 trial was 19.9 months, which is an improvement over the mOS range of 12.9 to 15.1 months reported in previous studies.

The CEO of Geneos, Niranjan Sardesai, highlighted the significance of the trial's results, noting that the GT-30 trial is unique in testing PTCVs in HCC, a cancer type with a low tumor mutational burden and an immune-excluded phenotype. Despite the small sample size, the study's outcomes are crucial for the field's progress, as they demonstrate the potential of PTCVs to improve clinical responses in a challenging treatment setting.

Immunological analyses from the trial showed that new T cell responses to the vaccine-encoded neoantigens were induced in all evaluated patients, with an expansion of the TCR repertoire in both peripheral blood and tumors. Single cell sequencing analyses revealed that the majority of these T cell clones were CD8 T effector memory cells, which are essential for inducing anti-tumor cytotoxicity.

At the 2024 AACR Annual Meeting, Geneos also presented data showing that reductions of at least 50% in patient ctDNA were observed in 40.7% of patients, with all such responses correlating with ongoing survival. The chief medical officer of Geneos, Ildiko Csiki, emphasized that the GT-30 study is the first to definitively demonstrate a personalized cancer vaccine enhancing the clinical response to anti-PD-1 therapy by inducing new, neoantigen-specific T cells that target the tumor.

The PTCVs used in the GT-30 study could include up to 40 neoantigens, and the correlation between the number of vaccine epitopes and the number of reactive epitopes post-vaccination suggests that a higher number of neoantigens in the vaccine could increase the effectiveness of tumor control. This approach differs from other personalized vaccine platforms, which often target a more limited selection of neoantigens.

Geneos Therapeutics is developing PTCVs using its proprietary GT-EPIC™ platform, aiming to target neoantigens from individual patient tumors to create personalized cancer treatments. The company is planning a potentially registrational clinical trial for advanced hepatocellular carcinoma.