Mary “Nora” Disis, MD, on Evaluating CAR-T PRGN-3005 in Ovarian Cancer

“Ovarian cancer is generally an intraabdominal tumor so we looked at intraperitoneal delivery, intravenous delivery, and intravenous delivery with chemotherapy to lymphodeplete T-cells—because we know that that lymphodepletion can make the CAR T-cells expand even more in the body.”

Although chimeric antigen receptor T-cell (CAR-T) therapies have had a transformative impact on the treatment landscape for some hematological malignancies, applying these novel therapies to treat solid tumors, such as ovarian cancer, has remained a challenge due to the limited persistence of some CAR T-cells and the difficulty of penetrating the solid tumor microenvironment.

PRGN-3005 is an investigational autologous CAR-T product currently being evaluated in a phase 1/1b clinical trial (NCT03907527) for the treatment of platinum-resistant ovarian cancer. PRGN-3005 targets MUC16, an antigen found on almost all advanced ovarian tumors. The product is also engineered to express a cytokine intended to improve persistence of the CAR T-cells. Results from the trial were reported in a talk entitled “Phase 1/1b study of PRGN-3005 autologous UltraCAR-T cells manufactured overnight for infusion next day to advanced stage platinum resistant ovarian cancer patients”, which was presented at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois.

In an interview with CGTLive™’s sister publication OncLive™, Mary “Nora” Disis, MD, director of University of Washington Medicine’s Cancer Vaccine institute, who coauthored the study, discussed the key findings that were presented and their implications for applying CAR-T for the treatment patients with solid tumors. She noted that in the study the CAR T-cells persisted for many weeks postinfusion and that in terms of safety, cases of cytokine release syndrome in the trial were mild. Disis also discussed the significance of delivery methods in this space and went over the various methods that were evaluated in the trial. She also touched on the efficacy seen with PRGN-3005, highlighting that in the cohort of patients in the trial who received PRGN-3005 intravenously with lymphodepletion, more than two-thirds of patients showed evidence of disease reduction.

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REFERENCE
1. Liao JB, Stanton SE, Chakiath M, et al. Phase 1/1b study of PRGN-3005 autologous UltraCAR-T cells manufactured overnight for infusion next day to advanced stage platinum resistant ovarian cancer patients. Presented at: the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois. Abstract #5590