Gemogenovatucel-T Receives FDA RMAT Designation for Advanced HRP Ovarian Cancer

FDA

The FDA has granted regenerative medicine advanced therapy (RMAT) designation to the investigational, personalized immunotherapy gemogenovatucel-T (Vigil) for the maintenance treatment of patients with newly diagnosed, advanced, stage IIIB/IV ovarian cancer who are homologous recombination proficient (HRP), have a high clonal tumor mutational burden (TMB), and who are in complete response (CR) following debulking surgery and frontline platinum-based doublet chemotherapy.¹

This decision was supported by findings from the ongoing phase 2b VITAL trial (NCT02346747), in which gemogenovatucel-T elicited a clinically meaningful and statistically significant overall survival (OS) benefit compared with placebo in the subgroup of patients with HRP ovarian cancer and a high clonal TMB who had achieved CR following treatment with standard-of-care frontline therapy. The median OS from randomization was not reached (NR) in the gemogenovatucel-T arm (n = 25) vs 26.9 months in the placebo arm (n = 20; HR, 0.342;log-rank P = .019).² At an April 2021 data cutoff date, updated OS data continued to show an improvement with gemogenovatucel-T vs placebo (HR, 0.417; P = .02). The 2-year OS rates in these respective arms were 92% and 55% (P = .002). The respective 3-year OS rates were 70% and 40% (P = .019).

“The RMAT designation for [gemogenovatucel-T] highlights the transformative capacity of our unique immunotherapy to benefit women battling advanced ovarian cancer,” David Shanahan, chief executive officer of Gradalis, stated in a news release.¹ “This important recognition affirms that [gemogenovatucel-T] 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 [gemogenovatucel-T] development efforts as we work to bring this investigational therapy to patients as rapidly as possible.”

Gemogenovatucel-T is a first-in-class immunotherapy that is designed to target the clonal mutation signals that are present within all cancer cells. The agent modifies tumors by using bi-shRNA to reduce furin, an enzyme that facilitates immunosuppressive TGF-β protein production. Gemogenovatucel-T also maximizes DNA expression of granulocyte-macrophage colony-stimulating factor, which stimulates the immune system and attracts immune system effector cells, such as T cells. Gemogenovatucel-T uses each patient’s individual tumor to generate a specifically targeted immune response that is relevant to each patient’s unique clonal tumor neoantigens.

The multicenter, double-blind VITAL trial enrolled patients ages 18 years or older with stage III or IV high-grade serous, endometrioid, or clear cell ovarian cancer who were in clinical CR after receiving surgery and 5 to 8 cycles of carboplatin- and paclitaxel-containing chemotherapy.³ Gemogenovatucel-T was manufactured from harvested tumor tissue. Patients received either 1 x 10⁷ cells per intradermal injection of gemogenovatucel-T or placebo once a month within 8 weeks after their last dose of chemotherapy for 4 to 12 doses.

The trial also demonstrated a positive trend for recurrence-free survival (RFS), its primary end point, with gemogenovatucel-T in the overall population. The median RFS from randomization was 11.5 months (95% CI, 7.5-NR) in the gemogenovatucel-T arm (n = 47) vs 8.4 months (95% CI, 7.9-15.5) in the placebo arm (n = 44; HR, 0.69; 90% CI; 0.44-1.07; 1-sided P = .078). The median follow-up was 40.0 months (IQR, 35.0-44.8) from the first dose of gemogenovatucel-T and 39.8 months (IQR, 35.5-44.6) from the first dose of placebo.

In the overall population, the median OS from the time of randomization and the time of procurement was not significantly longer in the gemogenovatucel-T arm vs the placebo arm (HR for OS from randomization, 0.71 [90% CI, 0.38-1.33; P = .18]; HR for OS from tissue procurement, 0.69 [90% CI, 0.37-1.29; P = .17]).

In the HRP population, the median RFS from randomization was 10.6 months with gemogenovatucel-T vs 5.7 months with placebo (HR, 0.386; P = .007).²

Furthermore, statistically significant RFS and OS improvements were seen in patients with BRCA wild-type disease.¹

References

1. Gradalis secures FDA regenerative medicine advanced therapy (RMAT) designation for Vigil (gemogenovatucel-T): an investigational personalized immunotherapy for advanced ovarian cancer. News release. Gradalis, Inc. February 5, 2025. Accessed February 5, 2025. https://www.globenewswire.com/news-release/2025/02/05/3021053/31499/en/Gradalis-Secures-FDA-Regenerative-Medicine-Advanced-Therapy-RMAT-Designation-for-Vigil-Gemogenovatucel-T-An-Investigational-Personalized-Immunotherapy-for-Advanced-Ovarian-Cancer.html
2. Rocconi RP, Ghamande SA, Barve MA, et al. Maintenance vigil immunotherapy in newly diagnosed advanced ovarian cancer: efficacy assessment of homologous recombination proficient (HRP) patients in the phase IIb VITAL trial. J Clin Oncol. 2021;39(15):5502. doi:10.1200/JCO.2021.39.15_suppl.5502
3. Rocconi RP, Grosen EA, Ghamande SA, et al. Gemogenovatucel-T (Vigil) immunotherapy as maintenance in frontline stage III/IV ovarian cancer (VITAL): a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Oncol. 2020;21(12):1661-1672. doi:10.1016/S1470-2045(20)30533-7