Personalized Immunotherapy Earns FDA RMAT Status in Advanced Ovarian Cancer

Developers designed gemogenovatucel-T as an immunotherapy platform that uses bi-shRNA to limit the enzyme furin, which facilitates immunosuppressive TGF beta protein creation, while increasing GM-CSF expression to stimulate the immune system by attracting T cells and other effector cells.

The FDA has granted Regenerative Medicine Advanced Therapy (RMAT) designation to gemogenovatucel-T (Vigil®), an investigational cellular immunotherapy, as a maintenance treatment for patients with newly diagnosed, homologous recombination proficient (HRP), advanced stage IIIb/IV ovarian cancer harboring high clonal tumor mutation burden (cTMB-H), according to a press release from the developer, Gradalis, Inc.¹

The agency confers RMAT status to advanced cellular and engineered therapies that may mitigate life-threatening or serious diseases based on preliminary activity. With RMAT designation, developers are eligible to facilitate more frequent FDA interactions and receive guidance on optimizing product development.

Supporting data for the designation came from the phase 2b VITAL trial (NCT02346747), in which investigators assessed treatment with gemogenovatucel-T vs placebo among patients with newly diagnosed, stage III/IV, frontline ovarian cancer. Prior data showed a trend towards improved recurrence-free survival (RFS), the trial’s primary end point, with the investigational agent across the overall population. Additionally, gemogenovatucel-T demonstrated significant improvements in RFS and overall survival (OS) among those with BRCA wild-type disease.

According to the press release, phase 1 data from an all-comer trial highlighted positive signs of activity across 19 different types of tumors with gemogenovatucel-T. Some patients who received the agent in this trial have remained on treatment at 48 months after beginning therapy.

“The RMAT designation for [gemogenovatucel-T] highlights the transformative capacity of our unique immunotherapy to benefit [patients with] advanced ovarian cancer,” David Shanahan, chief executive officer at Gradalis, stated in the press 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.”

Developers designed gemogenovatucel-T as an immunotherapy platform that uses bi-shRNA to limit the enzyme furin, which facilitates immunosuppressive TGF beta protein creation, while increasing GM-CSF expression to stimulate the immune system by attracting T cells and other effector cells. Investigators hypothesize that the agent may yield an immune response that specifically targets unique clonal tumor neoantigens by harnessing the tumor as an antigen source.

In the double-blind, phase 2 trial, 92 patients were assigned to receive gemogenovatucel-T at 1.0 x 10⁷ cells per dose via intradermal injection every 4 weeks for 4 to 6 doses or matched placebo.²

The trial’s primary end point was RFS, defined as the time from randomization or from surgery to the event of disease recurrence or progression or death following any cause. OS was a secondary end point.

Patients 18 years and older with presumptive stage IIIb, IIIc, or IV high-grade papillary serious, clear cell, endometrioid ovarian, fallopian tube, or primary peritoneal cancer were eligible for enrollment on the trial. Additional eligibility criteria included having no other malignancy unless in remission for at least 2 years, an ECOG performance status of 0 to 2 prior to laparoscopy or laparotomy, no prior hypersensitive reactions to taxanes or platinum-based treatment, and no prior allergies or sensitivity to gentamicin (Garamycin).

Those with surgery involving general anesthesia, radiotherapy, immunotherapy, or investigational agents within 4 weeks of randomization were ineligible for enrollment on the trial. Patients were also unable to enroll if they had histologically confirmed papillary serous adenocarcinoma of the uterus or disease involving myometrium/endometrium, systemic immunosuppressive therapy within 2 weeks of randomization, or a history of brain metastases.

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 6, 2025. https://tinyurl.com/4yr3mk8s
2. A trial of Vigil for participants with ovarian cancer (VITAL). ClinicalTrials.gov. Updated January 9, 2025. Accessed February 6, 2025. https://tinyurl.com/4k5cduwp