A phase I single-arm, open-label trial of engineering tumor-infiltrating lymphocytes with membrane-bound IL-7 for recurrent ovarian cancer.

5552 Background: Tumor-infiltrating lymphocytes (TILs) therapy has shown limited success in patients with recurrent ovarian cancer (OC). To improve TIL antitumor activity, we designed glycosylphosphatidylinositol-anchored membrane-bound interleukin-7 (mbIL-7-GPI) to engineer TILs (mbIL-7-TIL) through piggyBac transposon system. This study aimed to investigate the safety and efficacy of mbIL-7-TIL in recurrent OC patients. Methods: This is a single-center, investigator-initiated, open-label, single-arm phase 1 trial (NCT05468307). Tumor tissues were resected and transported to a GMP facility in a manufacturing cycle of 22-26 days. The cryopreserved infusion product was then shipped back to clinical center. All patients received 3-day lymphodepletion preconditioning (cyclophosphamide 20mg/kg/day every day and hydroxychloroquine 600mg on day one). This was followed by one-time infusion of PD-1 antibody (100 mg, sintilimab) and mbIL-7-TIL. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS). The exploratory endpoints were the pharmacokinetics /pharmacodynamics characteristics of mbIL-7-TIL. Results: Twenty patients were enrolled, and 18 patients were evaluable from Shanghai Tenth People's Hospital between 09/2021 and 01/2024, with a median follow-up of 8.7 (range, 2.9-18.8) months. Among the evaluable patients, the average metastasis lesions were 3.3 (range 1-9) and the average target lesion diameter was 58.7 (range 13-146) mm. The patients had received median 2.5 (range 1-9) lines of chemotherapy regimens. Of them, 10 (55.6%) and 2 (11.1%) received poly-ADP-ribose polymerase inhibitors and immune checkpoint inhibitors regimens. The median counts of infused cells was 2.7 ×10 9 (range, 1.2×10 9 -6.5×10 9 ) with a median mbIL-7 positive rate of 53.0% (range, 10.7%-98.5%). The most common treatment-emergent adverse events (TEAE) were elevated C-reactive protein levels (33%), fever (33%), and fatigue (11%). Only one patient experienced grade 3 TEAE (neutropenia). No grade 5 events occurred. Most of AEs were grade 1 or grade 2 and could be alleviated or cured by symptomatic treatment. The investigator-assessed confirmed ORR was 33.3% (95% CI: 16.3-56.3%) among which 2 (11.1%) patients were complete response (CR) and 4 (22.2%) patients were partial response (PR); DCR was 83.3% (95% CI: 60.8-94.2%). Median PFS was 5.5 (range, 1.0-14.1) months. Median OS was not reached. Six-month and 12-month OS rates were 75.6% (95% CI: 57.4-99.6%) and 68.8% (95% CI: 49.3-95.9%), respectively. Conclusions: Infusion of mbIL-7-TIL has acceptable safety and potent efficacy in recurrent OC patients who have limited treatment options. Clinical trial information: NCT05468307 .