Abstract P2-12-23: A phase 2 trial combining tiragolumab and atezolizumab with neoadjuvant or first line chemotherapy for triple negative breast cancer (SKYLINE)

Abstract Introduction: TIGIT is an immune inhibitory receptor that is a member of the Ig superfamily and that acts to limit anti-tumor immune responses in the context of the tumor microenvironment. TIGIT expression has been shown to be elevated in the tumor microenvironment in many human tumors and is coordinately expressed with other immune checkpoints such as PD-1/PD-L1. Prior works identified that expression of both PD-1 and TIGIT at the surface of CD4+ T lymphocytes is increased in presence of an immunosuppressive subset of cancer-associated fibroblasts (CAF) which express FAP (Fibroblast Activated Protein). Interestingly, new advanced metabolic imaging tracers, such as FAPI-46, could allow whole body imaging and quantitative mapping of FAP+ CAF and might represent a predictive marker of immunotherapy efficacy. SKYLINE is a phase 2 trial exploring the use of an anti-TIGIT therapy, tiragolumab, in combination with anti PD-L1 atezolizumab and chemotherapy in patient with triple negative breast cancer (TNBC), as neoadjuvant (cohort A) or first line (cohort B) therapy. Methods: SKYLINE (NCT06175390) is an ongoing trial in at Institut Curie Hospitals (France), prospectively enrolling 160 patients with TNBC (ER & PR<10%, HER2-). In cohort A, patients with stage II-III TNBC undergo neoadjuvant therapy that consists in a sequential use of nab-paclitaxel, carboplatin, atezolizumab and tiragolumab at standard doses for four 3-weeks cycles, followed by AC, atezolizumab and tiragolumab for four 3-weeks cycles, before curative surgery. Patients in cohort A could also receive additional atezolizumab and tiragolumab in the adjuvant setting. In cohort B, patients with de novo or relapsed stage IV TNBC receive nab-paclitaxel, atezolizumab and tiragolumab (4-weeks cycles) until disease progression or unacceptable toxicity. The study primary objective focuses on anti-tumor efficacy: pCR rate and 6-months PFS rate in cohorts A and B, respectively. Multiomics characterization of repeated tissue samples, blood samples and imaging (including next generation imaging with 68Ga-FAPI-46 PET/CT) is planned to better understand and predict the efficacy of immuno-chemotherapy in patients with TNBC. Acknowledgments SKYLINE is promoted by Institut Curie and supported by Roche, Institut Roche and ANR as part of the PIA France 2030 with the funding of the CASSIOPEIA RHU (ANR-21-RHUS-0002). Disclosures FC Bidard received personal fees (advisory board) from Roche. Citation Format: Francois-Clement Bidard, Romain-David Seban, Laurence Champion, Nina Jehanno, Anne Vincent-Salomon, Irene Buvat, Julien Fouque, Toulsie Ramtohul, Agathe Peltier, Diana Bello-Roufai, Florence Coussy, Fatima Mechta-Grigoriou. A phase 2 trial combining tiragolumab and atezolizumab with neoadjuvant or first line chemotherapy for triple negative breast cancer (SKYLINE) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-12-23.