KEY TAKEAWAYS
- The TUNINTIL study phase 3 trial aimed to investigate the enhanced efficacy and safety of TIL therapy in metastatic melanoma.
- The primary endpoint of the study was to determine safety of TILT-123.
- Researchers observed the safety and feasibility of combining TILT-123 and TIL therapy in metastatic melanoma pts.
Tumor Infiltrating Lymphocyte (TIL) therapy has demonstrated efficacy in metastatic melanoma. Oncolytic adenovirus TILT-123 (igrelimogene litadenorepvec), armed with TNF-alpha and IL-2, enhances TIL cytotoxicity without requiring preconditioning chemotherapy or postconditioning IL-2.
Tine J. Monberg and her team aimed to assess the safety and feasibility of combining TILT-123 and TIL therapy in metastatic melanoma patients (pts).
The study performed an inclusive analysis within a phase I, open-label, 3+3 dose-escalating multicenter trial, enrolling pts with stage IV melanoma. Participants received multiple intravenous and intratumoral injections of TILT-123 and one- or two-time TIL treatments. TILs were cultivated from resected tumor tissue and administered without pre- or post-conditioning regimens. The primary endpoint focused on evaluating the safety of TILT-123, while secondary endpoints included both safety and efficacy in combination with TILs.
About 16 pts with CPI-resistant progressive cutaneous (7), mucosal (5), and uveal (4) MM, with a median age of 65.5 years (25-75), were enrolled in the study. The most frequently reported adverse events (AEs) related to TILT-123 included fever (63%) and pain at the injection site (44%), while the most frequent AEs related to TIL therapy were fever (50%) and chills (24%). No dose-limiting toxicity (DLTs) was observed, and the combination of TILT-123 and TIL therapy did not increase the severity of AEs. 31% percent of pts experienced treatment-related serious AEs.
In d78 imaging, RECIST1.1 responses were observed in two pts, with a disease control rate of 38% (6/16). Responders included one pts with an ongoing partial response (cutaneous) and one with a durable complete response (mucosal). Additionally, 2 pts (uveal and cutaneous) exhibited long-lasting stable disease (>10 months). PET evaluation on d78 revealed disease control in 6/13 evaluable pts, including 4 partial or minor responses. On d36, after 4 injections of TILT-123 and before TILs, 4 partial or minor responses were seen in PET.
The study concluded that concurrent administration of TILT-123 and TIL therapy demonstrates safety and feasibility in patients with metastatic melanoma, with notable clinical efficacy observed in challenging melanoma subtypes.
The study is sponsored by TILT Biotherapeutics Ltd.
Source: https://cslide.ctimeetingtech.com/immuno23hybrid/attendee/confcal/show/session/10
Clinical Trial: https://clinicaltrials.gov/study/NCT04217473
Monberg T J, et al. (2023). “Safety and Efficacy of Combined Treatment with Tumor Infiltrating Lymphocytes (TILs) and Oncolytic Adenovirus TILT-123 for Patients with Metastatic Melanoma – Results from a Phase I Trial.” Presented at ESMO IO 2023 (Abstract 48O).
