Maintenance Gemogenovatucel-T Shows Survival Benefit in cTMB-High/HRP Ovarian Cancer

Maintenance therapy with gemogenovatucel-T (Vigil) conferred a clinically meaningful and statistically significant survival advantage over placebo to patients with newly diagnosed, advanced, stage IIIb-IV ovarian cancer with homologous recombination proficiency (HRP) and high clonal tumor mutation burden (cTMB-H) who are in complete response (CR) after debulking surgery and frontline platinum-based doublet chemotherapy, according to updated findings from the phase 2 VITAL trial (NCT02346747).^1,2

Among patients in the cTMB-H/HRP population who received gemogenovatucel-T (n = 11), the Kaplan-Meier (KM)–estimated median overall survival (OS) was 68 months (95% CI, 30.2-not available [NA]) vs 19 months (95% CI, 15.6-NA) with placebo (n = 12; HR, 0.23; 95% CI, 0.06 to 0.83; 1-sided P = .008) The 7-year OS rates were 75% and8%, respectively (1-sided P = .03).

Notably, OS outcomes for all patients with cTMB-H status in the intention-to-treat (ITT) population were not significantly improved with gemogenovatucel-T (n = 31) vs placebo (n = 34), with an HR of 0.69 (95% CI, 0.35-1.38; 1-sided P = .147).²

Recurrence-free survival (RFS), a key secondary end point, also favored gemogenovatucel-T over placebo (HR, 0.41; 95% CI, 0.13-1.35; 1-sided P = .066) in the cTMB-H/HRP subgroup.^1,2 The KM-estimated median RFS was 10 months (95% CI, 5.8-NA) vs 6 months (95% CI, 3.5-NA) with these respective regimens. Exploratory biomarker analyses reinforced the specificity of benefit to this patient subset.¹

Gemogenovatucel-T is a novel, triple function immunotherapy platform that modifies a patient’s tumor by using bi-shRNA to reduce furin, an enzyme which facilitates immunosuppressive TGF beta protein production, and to maximize DNA expression of GM-CSF, which stimulates the immune system and attracts key immune system effector cells, including T-cells.

Of note, the FDA granted regenerative medicine advanced therapy (RMAT) designation to gemogenovatucel-T based on previously reported data from VIGIL.

“Frontline ovarian cancer treatment protocols involving bevacizumab [Avastin], PARP inhibitors and PD-1/PD-L1 inhibitors have failed to improve OS in patients with HRP tumors,” John Nemunaitis, MD, chief scientific officer and co-founder of Gradalis stated in a news release. “Results published today validate our hypothesis by demonstrating that [gemogenovatucel-T] delivered a median OS of nearly 6 years compared to less than two years with placebo. With FDA RMAT fast track designation, we are positioned to accelerate development and bring this innovative therapy to patients sooner.”

What is the design of the VITAL trial?

The multicenter, double-blind, placebo-controlled study enrolled 91 patients with newly diagnosed stage IIIb-IV epithelial ovarian cancer who achieved a clinical complete response after undergoing debulking surgery and platinum-based chemotherapy in the first line.^1,2 Of note, the study enrolled both HRP and homologous recombination–deficient patients.

Eligible patients were randomly assigned 1:1 to receive gemogenovatucel-T (n=47) or placebo (n=44) as maintenance therapy.

The study’s primary end point was OS in the HRP population. Secondary and preplanned end points included the correlation of cTMB-H, clonal neoantigen–high, and intertumor heterogeneity with OS and relapse-free survival (RFS) from random assignment. Ad hoc analysis of RFS and OS from the time of tissue procurement was also performed.

Across all 91 patients enrolled, the majority (>90%) had high-grade serous ovarian cancer and received standard frontline platinum-based chemotherapy before entering the study.

In the cTMB-H/HRP subgroup, the median age of patients was 66.0 years (interquartile range [IQR], 62.0-71.5) in the gemogenovatucel-T arms and 64.5 (IQR, 61.5-67.3) in the placebo arm. Most patients were 65 years of age or older (72.7%) and had an ECOG performance status of 1 (63.6%) in the gemogenovatucel-T arm compared with half and 33.3% of patients in the placebo arm, respectively. The majority of patients were White (gemogenovatucel-T, 100%; placebo, 91.7%), not Hispanic or Latino (100%; 91.7%), had FIGO stage III disease (72.7%; 91.7%), had received adjuvant chemotherapy in the front line (72.7%; 91.7%), had microscopic/no evidence of disease after frontline surgery, and had high-grade serous carcinoma (90.9%; 100.0%).

The median number of chemotherapy cycles received was 6 (IQR, 6.0-6.0) in both arms. The median number of days from patients’ last administered chemotherapy dose to their first dose of gemogenovatucel-T or placebo was 42.0 (IQR, 40.0-50.0) and 44.5 (IQR, 35.8-49.0), respectively.

What additional translational data and bioinformatic analyses were reported from VITAL?

Molecular profiling demonstrated that the vaccine maintained the patient’s clonal mutational and neoantigen landscape, with a high concordance between baseline and post-treatment samples (R² = 0.98). Additionally, higher clonal neoantigen burden and lower intratumor heterogeneity were associated with improved clinical outcomes, supporting the biologic rationale for targeting clonal tumor signals to elicit durable antitumor immune responses.

In blinded post hoc bioinformatic analyses aimed at identifying mutation signatures associated with OS benefit, whole-exome sequencing was performed across all enrolled patients.¹ An OS advantage was observed in patients who received gemogenovatucel-T versus placebo in the cTMB-H group, with an HR above or equal to 0.741. Conversely, no difference in OS was observed between gemogenovatucel-T and placebo in the cTMB-low subset (HR, 1.36, 1-sided P = .696).² Moreover, the HRP patients with a cTMB of 0.658 or higher achieved an OS of 68 months vs 22 months with gemogenovatucel-T vs placebo, respectively (HR, 0.22; 1-sided P = .007). These data further indicated that patients with cTMB-H, HRP disease might derive greater OS benefit from maintenance therapy with gemogenovatucel-T than those without.¹

What was the safety profile of gemogenovatucel-T in this study?

Safety was evaluated in the full patient population (n = 91), and investigators deemed gemogenovatucel-T to be well tolerated. No grade 3 or higher treatment-related adverse effects (AEs) and no long-term safety signals, including myelodysplastic syndrome or acute myeloid leukemia, were observed over a median follow-up of 8.4 years. The most common AEs observed were low-grade injection-site reactions, and no treatment discontinuations were attributed to toxicity.

References

1. Gradalis’ Vigil demonstrates significant survival benefit in cTMB-H / HRP ovarian cancer patients; phase 2b VITAL trial analysis published in JCO – Precision Oncology. News Release. Gradialis. January 15, 2026. Accessed January 15, 2026. https://www.globenewswire.com/news-release/2026/01/14/3219157/0/en/Gradalis-Vigil-Demonstrates-Significant-Survival-Benefit-in-cTMB-H-HRP-Ovarian-Cancer-Patients-Phase-2b-VITAL-Trial-Analysis-Published-in-JCO-Precision-Oncology.html
2. Coleman RL, Rocconi R, Monk B, et al. Gemogenovatucel-T advantage in clonal tumor mutation burden–high ovarian cancer. J Clin Oncol. 2026; 10:e2500462.doi:10.1200/PO-25-00462