KEY TAKEAWAYS
- An interventional phase I trial aimed to assess the safety & efficacy of optimized TIL therapy in advanced solid tumors.
- The primary endpoint was to determine the DLTs.
- The study showcased that the modified TIL regimen was safe with promising responses across doses, paving the way for the Phase 1b trial.
Traditional tumor-infiltrating lymphocyte (TIL) therapy struggled due to harsh preconditioning (lymphodepletion) and potent but risky IL-2, hindering its use in cancer patients.
Qing Xu and his research team aimed to analyze the safety and efficacy of an optimized low-dose lymphodepletion and infusion regimen without IL-2 administration in TIL therapy for advanced solid tumors through a phase I study.
The study employed a standard 3+3 dose-escalation design, with the primary endpoint being the dose-limiting toxicities (DLTs) frequency. Patients received cyclophosphamide infusions (25 mg/kg/day) from day -5 to day -3 and hydroxychloroquine orally (600 mg once) on day -5. On day 0, TILs were intravenously administered post anti-PD-1 antibodies (100 mg per patient, sintilimab). Adverse events (AEs) were assessed using Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, and clinical responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
The DLT analysis included 3 patients at each TILs dose level: 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, 10 participants (9/10 with PD-1 antibody resistance) underwent TIL infusion without observing any DLTs.
The clinical responses were evident across dose levels, indicating the modified regimen’s safety. The recommended dose (RD) of TILs can be defined within a broad range. Phase 1b is anticipated to commence shortly. Shanghai Juncell Therapeutics Co., Ltd funded the research.
Source: https://cslide.ctimeetingtech.com/immuno23hybrid/attendee/confcal/show/session/34
Clinical Trial: https://clinicaltrials.gov/study/NCT05417750
Xu Q. et al. ‘’A phase I study of tumor-infiltrating lymphocytes (TILs) in advanced solid tumors used an optimized regimen: MIZAR trial.’’ Presented at the ESMO-IO 2023. (Presentation Number 63TiP).
