The FDA has granted Regenerative Medicine Advanced Therapy (RMAT) designation to Gemogenovatucel-T (Vigil), a novel personalized cellular immunotherapy developed by Gradalis for treating advanced ovarian cancer. The designation specifically targets patients with homologous recombination proficient (HRP) ovarian cancer and high clonal tumor mutation burden (cTMB-H).
The designation was supported by promising results from the ongoing phase 2b VITAL clinical trial (NCT02346747), which is evaluating the therapy in patients with newly diagnosed stage IIIb/IV ovarian cancer. The study, which has enrolled 92 patients, focuses on those who maintain complete response following debulking surgery and frontline platinum-based doublet chemotherapy.
Clinical Trial Results and Safety Profile
The VITAL trial has demonstrated encouraging outcomes, with positive trends observed in recurrence-free survival (RFS) across the overall study population. Notably, patients with BRCAwt molecular profiles showed statistically significant improvements in both RFS and overall survival (OS). Safety data from phase 1, 2a, and 2b trials indicate that Vigil has been well-tolerated by patients.
"The RMAT designation for Vigil highlights the transformative capacity of our unique immunotherapy to benefit women battling advanced ovarian cancer," stated David Shanahan, CEO of Gradalis. "This important recognition affirms that Vigil has the potential to extend patient survival and may offer a safer, more precise therapeutic approach to a population in urgent need of innovative solutions."
Mechanism of Action and Scientific Innovation
Vigil employs an innovative bi-shRNA mechanism designed to decrease furin levels while increasing GM-CSF expression. This dual action helps reduce immunosuppressive TGF beta protein production while enhancing immune system activation through the recruitment of crucial effector cells. The therapy's unique approach targets specific clonal tumor neoantigens present in individual patients, enabling a highly personalized treatment strategy.
Dr. John Nemunaitis, Chief Scientific Officer at Gradalis, emphasized the significance of targeting clonal neoantigens: "Immunotherapy has improved the outlook for many cancer patients, but its benefit has been limited to a fraction of the total patients in each tumor type. Targeting clonal neoantigens may be key to improving this situation."
Future Implications and Development
Recent research published in Cancers has highlighted the crucial role of clonal neoantigens in cancer immunotherapy, potentially explaining Vigil's observed survival benefits. The findings suggest that cancers with higher levels of clonal neoantigens may be more responsive to immunotherapy approaches, including checkpoint inhibitors.
The VITAL trial continues to progress, with an estimated completion date of December 2025. Gradalis is actively working to advance the development of Vigil, aiming to bring this promising therapy to patients as quickly as possible while maintaining rigorous scientific and safety standards.
