Gradalis, a clinical-stage biotechnology company, has announced striking results from its Phase 2b VITAL trial, showing that its autologous tumor-cell immunotherapy, Vigil (Gemogenovatucel-T), delivers a significant survival advantage in advanced ovarian cancer patients.

 

The updated analysis, published in JCO – Precision Oncology, highlights a clinically meaningful and statistically significant overall survival (OS) benefit in patients with clonal tumor mutational burden-high (cTMB-H) and homologous recombination proficient (HRP) tumors—a group historically resistant to standard therapies.

 

“Frontline ovarian cancer treatment protocols involving bevacizumab, PARP inhibitors and PD-1/PD-L1 inhibitors have failed to improve overall survival 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. 

 

"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 Vigil. 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. 

 

"With FDA RMAT Fast Track designation, we are positioned to accelerate development and bring this innovative therapy to patients sooner,” said John Nemunaitis, Gradalis’ Chief Scientific Officer and co-founder.

 

The randomized, double-blind, placebo-controlled Phase 2b VITAL trial enrolled 91 patients with newly diagnosed Stage IIIb–IV epithelial ovarian cancer who achieved a complete response after debulking surgery and frontline platinum-based chemotherapy. 

 

Vigil was well-tolerated across all patients, with no Grade 3 or greater related adverse events and no long-term safety concerns, including MDS or AML, over 8.4 years of follow-up. The most common adverse events were mild injection-site reactions, and no discontinuations were due to toxicity.

 

Molecular profiling confirmed that the vaccine preserved patients’ clonal mutational and neoantigen profiles. Patients with higher clonal neoantigen loads and lower intratumor heterogeneity experienced the greatest survival benefit, supporting Vigil’s mechanism of targeting clonal signals to drive durable immune responses.