Gradalis' Vigil Immunotherapy Shows Nearly Six-Year Survival Benefit in Ovarian Cancer Subset
Key Insights
Vigil demonstrated a median overall survival of 68 months versus 19 months for placebo in ovarian cancer (search) patients with high clonal tumor mutational burden and homologous recombination proficiency (HR=0.23; p=0.008).
The Phase 2b VITAL trial showed a 7-year overall survival rate of 45% with Vigil compared to 8% with placebo in the molecularly defined patient subset.
The autologous tumor-cell immunotherapy exhibited an excellent safety profile with no Grade 3 or greater treatment-related toxicities across 91 patients over 8.4 years of follow-up.
Gradalis (search) announced compelling results from its Phase 2b VITAL trial showing that Vigil (gemogenovatucel-T), an autologous tumor-cell immunotherapy, delivered a statistically significant overall survival benefit in a molecularly defined subset of ovarian cancer (search) patients. The updated analysis, published in JCO – Precision Oncology, demonstrates a median overall survival of nearly six years in patients with clonal tumor mutational burden-high (cTMB-H) and homologous recombination proficient (HRP) disease.
Substantial Survival Advantage in Targeted Population
The randomized, double-blind, placebo-controlled Phase 2b VITAL trial enrolled 91 patients with newly diagnosed Stage IIIb–IV epithelial ovarian cancer (search) who achieved clinical complete response following debulking surgery and frontline platinum-based chemotherapy. In the cTMB-H/HRP subset comprising 23 patients (Vigil: 11; Placebo: 12), Vigil demonstrated a median overall survival of 68 months versus 19 months for placebo (HR=0.23; p=0.008).
The survival benefit extended to long-term outcomes, with a 7-year overall survival rate of 45% for Vigil-treated patients compared to 8% for placebo recipients in this molecularly defined population. Recurrence-free survival also favored Vigil treatment (10 vs. 6 months; HR=0.41), with benefit confirmed through Restricted Mean Survival Time analysis.
"Frontline ovarian cancer (search) treatment protocols involving bevacizumab, PARP inhibitors and PD-1 (search)/PD-L1 (search) inhibitors have failed to improve overall survival in patients with HRP tumors," stated John Nemunaitis, MD, Gradalis (search)' Chief Scientific Officer and co-founder. "Results published today validate our hypothesis demonstrating that Vigil delivered a median OS of nearly six years compared to less than two years with placebo."
Biomarker-Driven Patient Selection
The trial employed blinded post-hoc bioinformatic analyses using whole exome sequencing to identify mechanistic mutation signatures associated with overall survival advantage. Exploratory biomarker analyses reinforced the specificity of benefit to HRP tumors with high clonal mutational burden, providing a foundation for precision medicine approaches in ovarian cancer (search) treatment.
Molecular profiling confirmed that Vigil preserved patients' clonal mutational and neoantigen profiles (R²=0.98). Higher clonal neoantigen load and lower intratumor heterogeneity correlated with improved outcomes, supporting the mechanistic rationale for targeting clonal signals to drive durable immune responses.
Exceptional Safety Profile
Safety analyses conducted across the entire randomized population of 91 patients demonstrated excellent tolerability. Treatment was well-tolerated with no Grade 3 or greater related adverse events and no long-term safety signals such as myelodysplastic syndrome or acute myeloid leukemia over 8.4 years of follow-up. The most common events were mild injection-site reactions, and no discontinuations were attributed to toxicity.
Novel Immunotherapy Mechanism
Vigil represents a triple function immunotherapy platform that modifies patients' tumors using bi-shRNA technology to reduce furin (search), an enzyme facilitating immunosuppressive TGF beta (search) protein production, while maximizing GM-CSF expression to stimulate immune system activation. By utilizing patients' own tumors as antigen sources, Vigil elicits immune responses specifically targeted to each patient's unique clonal tumor neoantigens.
Regulatory Pathway and Future Development
The FDA granted Vigil Regenerative Medicine Advanced Therapy (RMAT) designation based on the statistically significant and clinically meaningful overall survival improvement. This designation supports expedited development toward Phase 3 confirmatory trials for patients with cTMB-H/HRP ovarian cancer (search).
Vigil represents the first cellular immunotherapy to demonstrate longer-term survival benefits in a randomized controlled trial of patients with solid tumors. The company's Phase 2b study results have been published in Lancet Oncology and Gynecologic Oncology, with presentations at the American Society of Clinical Oncology.