Gemogenovatucel-T Triples Overall Survival in High-Risk HRP Ovarian Cancer

Analysis of the phase 2 VITAL trial (NCT02346747) demonstrated a statistically significant and clinically profound overall survival (OS) advantage with gemogenovatucel-T (Vigil) in high-risk patients with ovarian cancer, specifically those with homologous recombination–proficient (HRP) tumors and high clonal tumor mutation burden (cTMB-H).^1,2

The primary end point of the study was successfully met, revealing that patients in the cTMB-H/HRP subgroup treated with gemogenovatucel-T achieved a median OS of 68 months, compared with just 19 months for those receiving a placebo. This constitutes a greater than 4-year survival benefit (HR, 0.23; P =.008). The treatment effect proved durable, with a 45% survival rate at 7 years for the gemogenovatucel-T group vs 8% for the placebo group.

Due to the prespecified hierarchical testing method, relapse-free survival (RFS) results were not considered statistically significant after the second end point failed to reach significance. However, the data were presented as potentially clinically significant:

• Median RFS (cTMB-H/HRP): 10 months for gemogenovatucel-T vs 6 months for placebo (HR, 0.41; P =.066).

An additional analysis investigated a larger patient subset with a BRCA-1/2 wild-type genotype and a cTMB-H profile (n = 42). This group also demonstrated significant improvements with gemogenovatucel-T, suggesting a potential future direction for development:

• OS: Not available for gemogenovatucel-T vs 36 months for placebo (HR, 0.37; P =.013).
• RFS: 11 months for gemogenovatucel-T vs 8 months for placebo (HR, 0.49; P =.044).

A key advantage of gemogenovatucel-T is its favorable safety profile. No significant difference in toxic effects was observed compared with placebo, and notably, no grade 3 or higher treatment-related adverse events occurred in the gemogenovatucel-T arm.

Trial Overview

The findings are based on a whole-exome sequencing bioinformatic analysis of all 91 patients enrolled in the VITAL trial. This was a multicenter, double-blind, 1:1 randomized, placebo-controlled phase 2 study.

• Patient population: Adult females with newly diagnosed, advanced stage IIIb-IV ovarian cancer who were in complete clinical response following debulking surgery and frontline platinum-based doublet chemotherapy.
• Intervention: Patients received either gemogenovatucel-T or a placebo as maintenance therapy.

The therapeutic benefit of gemogenovatucel-T was highly specific to the biomarker profile of cTMB-H combined with HRP status. Analyses of other patient subgroups did not show a similar survival advantage, reinforcing the precision of this biomarker-guided approach.

• cTMB-high / non-HRP patients: This group (with BRCA-m/HRD profiles) showed no OS advantage with the treatment (HR, 0.99; P = .488).
• cTMB-high / intent-to-treat population: When all cTMB-H patients (both HRP and non-HRP) were analyzed together, the OS difference was not statistically significant (HR, 0.69; P =.147).
• cTMB-low / HRP patients: Patients in the HRP group with low clonal tumor mutation burden also demonstrated no difference in OS between treatment and placebo (HR, 1.36; P =.696).

Broader Context and Future Implications

Gemogenovatucel-T is a DNA-engineered, triple-function immunotherapy that utilizes a patient's autologous tumor cells as a source for the complete matrix of tumor-related clonal signals. Its mechanism is designed to promote tumor-specific antigen presentation,activate dendritic cells, and enable tolerance escape.

The study strongly supports the hypothesis that clonal mutations—progenitor mutations present in all cancer cells—are the most relevant targets for an effective immune response. This aligns with other research indicating that high cTMB correlates significantly with clinical benefit from immunotherapy, whereas subclonal mutations do not.

The results are particularly noteworthy in the context of modern oncology drug approvals. Between 2006 and 2023, only 22% of FDA oncology approvals were based on an OS advantage, with the median benefit being just 2.4 months. The greater than 4-year OS advantage demonstrated by gemogenovatucel-T in this trial is exceptional and underscores its potential impact.

This has been recognized by the FDA, which granted fast track regenerative medicine advanced therapy designation in January 2025 to expedite the development and review of gemogenovatucel-T for the cTMB-H/HRP ovarian cancer population.

A phase 3 study is planned to validate these highly encouraging results, with the ultimate goal of establishing gemogenovatucel-T as a new standard of care for this underserved patient population.

“Based on these data, we hypothesized that patients with an HRP profile and high clonal tumor mutation burden might achieve greater response when undergoing maintenance therapy with [gemogenovatucel-T],” said John Nemunaitis, MD, Gradalis’ chief scientific officer and co-founder, in a news release.³ “Results published today validate our hypothesis demonstrating that [gemogenovatucel-T] delivered a median OS of nearly [6] years compared [with] less than [2] years with placebo.”

REFERENCES

1.Coleman R, Rocconi R, Monk B, et al. Gemogenovatucel-T advantage in clonal tumor mutation burden-high ovarian cancer. JCO Precis Oncol 10, e2500462(2026)Volume 10doi: 10.1200/PO-25-00462

2.A trial of Vigil for participants with ovarian cancer (VITAL). ClinicalTrials.gov. Updated October 29, 2025. Accessed February 2, 2026. https://clinicaltrials.gov/study/NCT02346747

3.Gradalis’ Vigil demonstrated significant survival benefit in cTMB-H/HRP ovarian cancer patients; phase 2b VITAL trial analysis published in JCO-Precision Oncology. News release. Gradalis, Inc. Published January 15, 2026. Accessed February 2, 2026. https://tinyurl.com/4pddurnp