A phase I single-arm, open-label trial of engineering tumor-infiltrating lymphocytes with membrane-bound IL-7 for recurrent ovarian cancer.
Authors: Jing Guo, Yuliang Wu, Chen Huang, Wei Huang, Jinye Ding, Yao Ge, Jihui Zhu, Weihui Shi, Guihai Ai, Shupeng Liu, Weina Wang, Ning Luo, Caixia Li, Chen Rong, Binghui Zhao, Huajun Jin, Zhongping Cheng
Journal: Journal of Clinical Oncology (2024)

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 .