Phase 2 OVAFIT-TIL CD137 (4-1BB)–selected autologous TIL + PD-1 blockade

This Phase 2 study at the Medical University of South Carolina (MUSC) tests an autologous tumor-infiltrating lymphocyte (TIL) product that is metabolically optimized and enriched for CD137+ (4-1BB+) activated T cells, aiming to improve persistence and tumor killing in recurrent epithelial ovarian cancer. Patients first undergo surgical resection of an accessible metastatic lesion so MUSC can manufacture and expand the personalized TIL product; this is followed by nonmyeloablative lymphodepletion with fludarabine (a purine analog that inhibits DNA synthesis) plus cyclophosphamide (an alkylating DNA crosslinker), then TIL infusion and high-dose interleukin-2 (IL-2) to support T-cell expansion. After recovery, participants receive consolidative systemic therapy combining oral cyclophosphamide (metronomic immunomodulatory chemotherapy), bevacizumab (Genentech/Roche’s anti-VEGF-A antibody), and pembrolizumab (Merck’s PD-1 antibody). The key scientific angle is layering a next-step engineered/selected TIL platform onto a consolidation regimen that has shown activity in recurrent ovarian cancer. Today’s care in this setting is sequential systemic therapy based on platinum sensitivity and biomarkers (platinum re-challenge when sensitive; PARP inhibitors in BRCA/HRD-selected settings; and later-line chemo ± bevacizumab, with ADC options such as mirvetuximab in FRα-high disease), so this explores a personalized cell-therapy “reset” plus anti-angiogenic + checkpoint maintenance.