Phase I trial and preclinical data of ACT using neoantigen-reactive TIL for patients with advanced epithelial and ICB-resistant solid cancers

• Published in: Immuno-oncology technology 2024-12, p.101030, Article 101030
• Main Authors: Palomero, Jara, Galvao, Vladimir, Creus, Immaculada, Lostes, Julia, Aylagas, Miriam, Marín-Bayo, Albert, Rotxés, Marta, Sanz, Marta, Lozano-Rabella, Maria, Garcia-Garijo, Andrea, Yuste-Estevanez, Anna, Grases, Daniela, Díaz-Gómez, Judit, González, Jonatan, Navarro, Jose Fernandez, Gartner, Jared J., Braña, Irene, Villalobos, Xenia, Bayó-Puxan, Neus, Jiménez, Jose, Palazón, Anna N., Muñoz, Susana, Villacampa, Guillermo, Piris-Giménez, Alejandro, Barba, Pere, Codinach, Margarita, Rodríguez, Luciano, Querol, Sergi, Muñoz-Couselo, Eva, Tabernero, Josep, Martín-Lluesma, Silvia, Gros, Alena, Garralda, Elena
• Format: Article
• Language: English
• ISSN: 2590-0188; 2590-0188
• DOI: 10.1016/j.iotech.2024.101030

ACT of ex vivo expanded TIL can mediate objective tumor regression in 28-49% of metastatic melanoma patients. However, the efficacy of TIL therapy in most epithelial cancers remains limited. We present the design of a phase I clinical study that aims to assess the safety and efficacy of NEXTGEN-TIL, a TIL product selected based on ex vivo neoantigen recognition, in patients with advanced epithelial tumors and ICB-resistant solid tumors. PreREP TIL cultures expanded in high dose IL-2 (HD-IL-2) from patients with metastatic solid tumors were screened for recognition of autologous TCL and/or neoantigens. 6 GMP validations of preREP TIL expansion were performed and TIL cultures from these 6 intermediate products were selected to perform the clinical scale GMP validation of the REP. TIL expanded in 82% of patient-derived tumor biopsies across different cancer types and these contained tumor- and neoantigen-reactive T cells. During GMP-validations, a variable number of TILs expanded, constituting the intermediate products (preREP). Three finished products (REP) were manufactured which reached cell doses ranging from 4.3e9 to 1.1e11 and met the established specifications. The NEXTGEN-TIL clinical trial entails a first expansion of TIL from tumor fragments in HD-IL-2 followed by TIL screening for neoantigen-recognition and REP of selected neoantigen-reactive TIL cultures. Treatment involves a classical non-myeloablative lymphodepleting chemotherapy followed by NEXTGEN-TIL product administration together with HD-IL-2. NEXTGEN-TIL consists of selected neoantigen-reactive TIL and aims to potentially improve efficacy in patients with epithelial and ICB-resistant tumors, with a safety profile like traditional TIL. •The NEXTGEN-TIL trial is a phase I clinical study that aims to evaluate the feasibility and safety of neoantigen reactive TIL for the treatment of epithelial and ICB-resistant solid cancers.•Patients will receive bridge therapy while TIL are manufactured and, upon progression and if neoantigen reactive TIL are detected, they will enroll in the treatment phase involving non-myeloablative lymphodepleting chemotherapy followed by the TIL product administration together with high-dose IL-2.•The NEXTGEN-TIL product consists of ex vivo expanded TIL selected based on neoantigen-recognition.•Approximately 80% of tumor biopsies gave rise to expanded TIL regardless of specific tumor type or prior therapy.•The vast majority of patient biopsies harbored TIL targeting ne