Gemogenovatucel-T Exhibits Survival Benefit in Epithelial Ovarian Cancer

Maintenance therapy with gemogenovatucel-T (Vigil), an autologous tumor-cell immunotherapy, exhibited a significant survival benefit among select patients with newly diagnosed stage IIIb to IV epithelial ovarian cancer, according to findings from the phase 2b VITAL/CL-PTL-119 trial (NCT02346747) published in JCO Precision Oncology.¹

Specifically, among patients with high clonal tumor mutation burden (cTMB-H) in the homologous recombination-proficient (HRP) population, treatment with gemogenovatucel-T conferred a Kaplan Meier (KM)-estimated median overall survival (OS) of 68 months (95% CI, 30.2-not available [NA]) vs 19 months (95% CI, 15.6-NA) among patients treated with placebo (HR, 0.23; 95% CI, 0.06-0.83; P = .008). Moreover, per restricted mean survival time (RMST) analysis, the median OS was 63 months (95% CI, 45-81) vs 33 months (95% CI, 16-49) in the respective arms (P = .007).

Among the overall intent-to-treat (ITT) population of those with cTMB-H status, the difference in OS between gemogenovatucel-T and placebo was not significant (HR, 0.69; 95% CI, 0.35-1.38; P = .147). The KM-estimated median relapse-free survival (RFS) in the HRP population was 10 months (95% CI, 5.8-NA) with gemogenovatucel-T vs 6 months (95% CI, 3.5-NA) with placebo (HR, 0.41; 95% CI, 0.13-1.35; P = .066). In the RMST analysis, it was 10 months (95% CI, 8-12) and 6 months (95% CI, 4-8) in the respective arms (P = .004).

“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. To determine mechanistic mutation signatures associated with OS advantage, we conducted blinded post-hoc analyses of the 91 patients treated in the VITAL trial,” John Nemunaitis, MD, chief scientific officer and co-founder of Gradalis, the developer of gemogenovatucel-T, stated in a news release on the VITAL results.² “Based on these data, we hypothesized that patients with an HRP profile and [cTMB-H] might achieve greater response when undergoing maintenance therapy with [gemogenovatucel-T].”

The multicenter, double-blind study randomly assigned patients with frontline ovarian cancer experiencing a clinical complete response following debulking surgery and adjuvant/neoadjuvant chemotherapy 1:1 to receive gemogenovatucel-T (n = 47) or placebo (n = 44) as maintenance therapy. Patients were stratified by extent of surgical cytoreduction and receipt of adjuvant or neoadjuvant chemotherapy.

Between patients in the cTMB-H/HRP groups assigned to gemogenovatucel-T (n = 11) or placebo (n = 12), the median age was 66.0 years (range, 51.0-84.0) vs 64.5 years (range, 49.0-79.0), and 100% vs 91.7% were White and non-Hispanic. A total of 63.6% vs 33.3% had an ECOG performance status of 1, 72.7% vs 91.7% had FIGO stage III disease, and 90.9% vs 100% had high-grade serous carcinoma. Moreover, 72.7% vs 91.7% received adjuvant chemotherapy, 72.7% vs 75.0% had microscopic frontline surgery residual disease status, and 8 patients vs 11 patients in each arm received subsequent anticancer therapies.

The primary end point of the trial was OS in the cTMB-H/HRP population. Secondary end points included OS in the ITT population, RFS in the HRP and ITT populations, and safety.

No grade 3 or higher treatment-related adverse effects (TRAEs) emerged in the gemogenovatucel-T population, with 4 emerging in the placebo group; 1 patient experienced high-grade bone pain, muscle weakness, syncope, and dyspnea. Grade 3 AEs not related to treatment in the investigational arm included single instances of arthralgia and maculopapular rash. A single patient in the gemogenovatucel-T arm experienced a dose interruption due to a grade 3 non–treatment-related instance of abdominal infection per investigator evaluation, with no dose reduction, discontinuation, or treatment death observed in the trial.

“Results published today validate our hypothesis demonstrating that [gemogenovatucel-T] delivered a median OS of nearly 6 years compared to less than 2 years with placebo. With FDA regenerative medicine advanced therapy [RMAT] fast track designation, we are positioned to accelerate development and bring this innovative therapy to patients sooner,” Nemunaitis concluded.²

References

1. Coleman RL, Rocconi R, Monk BJ, et al. Gemogenovatucel-T advantage in clonal tumor mutation burden–high ovarian cancer. JCO Precis Oncol. 2026;10:e2500462. doi:10.1200/PO-25-00462
2. 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. Gradalis. January 14, 2026. Accessed January 15, 2026. https://tinyurl.com/muvkkrys