63TiP - A phase I study of tumor-infiltrating lymphocytes (TILs) in advanced solid tumors used an optimized regimen: MIZAR trial

Background

The clinical usefulness of tumor-infiltrating lymphocyte (TIL) has been limited due to an intensive lymphodepletion regimen and high-dose intravenous interleukin-2 (IL-2) administration. We explore the low dose regimens of lymphodepletion and infusion without IL-2 administration in TIL therapy, which showed encouraging outcome in a case report. Thus, a phase I study to evaluate the safety and efficacy of optimized TIL-therapy regimen for the treatment of advanced solid tumors was conducted.

Trial Design

The phase 1a part used a conventional 3+3 dose-escalation design. The primary endpoint in the phase 1a part was the frequency of dose-limiting toxicities (DLTs). Patients received three consecutive daily infusions of cyclophosphamide (25 mg/kg/day) from day -5 to day -3, and oral administration of hydroxychloroquine (600 mg once) on day -5. On day 0, patients received a single intravenous adoptive transfer of TILs following the administration of anti-PD-1 antibody (100mg per patient, sintilimab). Adverse events (AEs) were assessed based on Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Clinical responses were assessed according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Three patients were planned for DLT analysis at each dose level of TILs infusion: level 1 (5.0×10⁹± 20% cells), level 2 (1.5×10¹⁰± 20% cells), level 3 (3.0×10¹⁰± 20% cells), and level 4 (4.5×10¹⁰± 20% cells). As of September 15, 2023, ten participants (9/10 with PD-1 antibody resistance) have been enrolled and underwent TIL infusion. None DLT was observed and the clinical responses were observed across different dose levels, suggesting the modified regimen is safe and the recommended dose (RD) of TILs can be defined within a broad range. The phase 1b part would be started in soon future.

Clinical trial identification

NCT05417750.

Legal entity responsible for the study

Shanghai Juncell Therapeutics Co., Ltd.

Funding

Shanghai Juncell Therapeutics Co., Ltd.

Disclosure

H. Jin: Financial Interests, Institutional, Funding: Shanghai Juncell Therapeutics Co., LTD. All other authors have declared no conflicts of interest.