Abstract OT2-10-04: Treatment of advanced or metastatic triple-negative breast cancer with adoptive therapy of PD1+ tumor-infiltrating lymphocytes (TILS001 trial)

Abstract Background Metastatic triple-negative breast cancer (mTNBC) exhibits a particularly poor clinical outcome, generally with rapid progression and worse overall survival (OS) than other BC subtypes. Among the few therapeutic options, chemotherapy-based combinations are associated with increased toxicity and limited survival benefit, being treatment with sequential single agents, such as paclitaxel considered an appropriate first-line regimen for the metastatic setting for PDL-1 negative patients. Herein, there is an urgent need for clinically active agents for the mTNBC. Adoptive cell transfer (ACT)-based immunotherapy using ex vivo activated and expanded tumor-infiltrating lymphocytes (TILs) has shown promising therapeutic outcomes in some patients with metastatic tumors. The identification, selection, and enrichment of tumor-reactive lymphocytes at the early stages of the ACT generation could enhance their clinical activity. Thus, the selection of reactive T cells, such as PD1-positive (PD1+) TILs, could improve the responses achieved in those settings. TILS001 trial aims to explore the safety, tolerability and efficacy of selected PD1+ T-cell infusion with a previous pre-selection of mRNA PD1-high expression in patients with mTNBC. Study design: TILs001 trial is an open-label, single-arm, multicenter phase I/II prospective study with a two-stage design evaluating treatment with PD1+ TILs infusion in advanced or mTNBC, defined as HER2 negative and Hormonal Receptor < 10%. The study involves three different parts before PD1+TILs treatment. Tumor samples evaluable for PD1 mRNA expression and life expectancy ≥6 months are mandatory for part 1. Patients with high levels of PD1 mRNA, defined by the pre-specified cutoff, candidates for receiving a first-line taxane-based containing regimen and with at least 1 accessible target lesion to generate TILs are eligible for part 2. Finally, once the complete expansion of PD1+TILs is reached, patients will receive the non-myeloablative lymphodepleting chemotherapy regimen followed by PD1+TIL infusion and IL-2 treatment. Allogeneic hematopoietic stem cell transplantation, immune system-related disease or clinically active cerebral metastasis are not allowed. The primary objectives are to evaluate the safety and tolerability of the PD1+ TIL product, as per incidence of grade 3-5 adverse events (AE) or any grade AE that leads to treatment discontinuation and to assess the efficacy of ACT therapy with selected PD1+ TILs in mTNBC in terms of progression-free survival (PFS) at 6 months. The secondary endpoints are clinical benefit rate at 6 months (CBR6), overall response rate, duration of response (DoR), PFS and OS. Further translational research including immunophenotyping, TCR sequencing and mutational analysis will also be performed. The first 3 patients will be included in a safety run-in phase where safety will be evaluated 24h after PD1+/TILs infusion (before IL-2 treatment) and a phase II stage where efficacy will be evaluated, which will include up to 20 patients. Patients will be enrolled in 4 sites in Spain. Recruitment is expected to start by July 2022 and to be completed within 24 months. This study is financially supported by the Asociación Española Contra el Cáncer (GCAEC19010PRAT). NCT05451784 Citation Format: Nuria Chic, Eva Ciruelos, Cristina Saura, Europa-Azucena Gonzalez, Luís Álvarez-Vallina, Juan José Lasarte, Alena Gros, Lorea Villanueva, Jordi Canes, Laura Angelats, Aleix Prat, Tomás Pascual, Marta Santisteban, Manel Juan. Treatment of advanced or metastatic triple-negative breast cancer with adoptive therapy of PD1+ tumor-infiltrating lymphocytes (TILS001 trial). [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-10-04.