Dr. Disis on the Rationale For Investigating PRGN-3005 With/Without Lymphodepletion in Ovarian Cancer

Mary “Nora” Disis, MD, director, University of Washington (UW) Institute of Translational Health Science, Center for Translational Medicine in Women's Health, dean, Research and Graduate Education, associate dean, Translational Science, Helen B. Slonaker Endowed Professor for Cancer Research, professor, medicine and oncology, adjunct professor, Obstetrics & Gynecology and Pathology, UW School of Medicine, discusses the rationale for investigating the efficacy and optimal delivery of PRGN-3005 autologous UltraCAR T cells in patients with advanced stage platinum-resistant ovarian cancer.

Although CAR T-cell therapies have shown substantial efficacy in hematologic diseases, attempts to utilize this drug class in solid tumors have been less successful, Disis begins. Challenges associated with the implementation of CAR T-cell therapy in this disease space include issues with T-cell penetration and limited T-cell persistence, she states.

In order to address these unmet needs, investigator's launched a phase 1/1b study (NCT03907527) to assess PRGN-3005, Disis states. PRGN-3005 is a novel therapy that targets the tumor antigen MUC16, which is commonly expressed in advanced ovarian cancers, Disis explains. PRGN-2005 was engineered to express MUC16, as well as a cytokine promoting T-cell longevity, she notes.

The trial enrolled patients with cisplatin-refractory ovarian cancer, Disis continues, noting that this disease subtype is often challenging to treat. PRGN-3005 autologous UltraCAR T-cells were administered with or without lymphodepletion, demonstrating tolerability and a reduction in overall tumor burden in heavily pretreated patients, Disis reports.

Intravenous delivery of PRGN-3005 led to dose-dependent T-cell expansion regardless of subsequent lymphodepletion. However, combining lymphodepletion with PRGN-3005 notably stabilized or decreased CA125 levels in 89% of patients.

The study also highlighted the effectiveness of PRGN-3005, with a single intravenous infusion after lymphodepletion resulting in a 67% reduction in tumor burden, while 2 infusions led to a 28% reduction. Importantly, PRGN-3005 exhibited an excellent safety profile, with no dose-limiting toxicities, neurotoxicity, or ophthalmologic adverse effects noted.

These results suggest that PRGN-3005 CAR T-cell therapy, with its engineered cytokine for prolonged T-cell activity, could overcome current limitations associated with the treatment of patients with difficult-to-treat ovarian cancer, Disis concludes.