Gradalis' Personalized Immunotherapy Gemogenovatucel-T Receives FDA RMAT Designation
The product, also known as Vigil, is being evaluated in the ongoing randomized, placebo-controlled phase 2b VITAL clinical trial.
Gradalis' Gemogenovatucel-T (also known as Vigil), an investigational personalized cellular immunotherapy currently being evaluated for the treatment of ovarian cancer, has received regenerative medicine advanced therapy (RMAT) designation from the FDA.1
The product is being evaluated in the ongoing randomized, placebo-controlled phase 2b VITAL clinical trial (NCT02346747) in patients with newly diagnosed, advanced stage IIIb/IV ovarian cancer who are homologous recombination proficient (HRP), have a high clonal tumor mutation burden (cTMB-H), and who remain in complete response after debulking surgery and frontline platinum-based doublet chemotherapy. According to the clinicaltrials.gov page, which was most recently updated on January 9, 2025, VITAL is active, but no longer recruiting new patients. It was initiated in February 2015 and has an estimated completion date of December 2025. The total enrollment for the study is listed as 92 patients. According to Gradalis, results from the study showing a statistically significant and clinically meaningful improvement in overall survival (OS) in patients with HRP ovarian cancer and cTMB-H informed the FDA's decision to grant the RMAT designation, which applies specifically to that indication.
“The RMAT designation for Vigil highlights the transformative capacity of our unique immunotherapy to benefit women battling advanced ovarian cancer,” David Shanahan, BS, the chief executive officer of Gradalis, said in a statement.1 “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. We continue to advance our Vigil development efforts as we work to bring this investigational therapy to patients as rapidly as possible.”
Vigil utilizes bi-shRNA with the intention of decreasing levels of furin and increasing expression of GM-CSF. Furin contributes to the production of TGF beta protein, which is immunosuppresive, and GM-CSF taps the immune system and draws in important immune system effector cells. Gradalis notes that Vigil is intended to bring about an immune response that is specifically targeted to the unique “clonal” tumor neoantigens found in a particular patient.
Gradalis stated that in the overall population treated in VITAL, Vigil demonstrated a positive trend for recurrence free survival (RFS), which constitutes the study’s primary end point. Furthermore, among a subgroup of patients with the BRCAwt molecular profile, statistically significant improvements in both RFS and OS, which constituted a secondary end point, were recorded. With regard to safety, Gradalis noted that Vigil was well-tolerated in phase 1, 2a, and 2b trials.
In December 2023, Gradalis highlighted a publication in Cancers that covered the important role of clonal neoantigens in immunotherapy research for oncology.2,3 The company stated that findings discussed in the paper may elucidate Vigil’s benefit to OS observed in clinical research.
“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,” John Nemunaitis, MD, the chief scientific officer of Gradalis, who coauthored the paper in Cancers, said in a December 2023 statement.2 “Targeting clonal neoantigens may be key to improving this situation. Clonal neoantigens are tumor initiating mutations and therefore found on the surface of all cells of a patient’s tumor. Clonal mutations expressed on the cancer surface provide a distinguishing difference between cancer cells and normal noncancer cells. Emerging research shows that targeting clonal mutations may be critical in achieving a durable clinical benefit. For example, cancers displaying high levels of clonal neoantigens have been shown to be more responsive to checkpoint inhibitors, a type of immunotherapy used in several tumor types. In multiple retrospective analyses of studies of lung cancer patients treated with CPIs, higher levels of clonal neoantigens are highly correlated with better patient outcomes.”
