Abstract 5179: Tumor microenvironment (TME) biomarkers of TIGIT and PD-L1 immune checkpoint blockade in cervical cancer: An exploratory biomarker analysis from SKYSCRAPER-04 (SKY04) study

Abstract Introduction: Immune checkpoint inhibitors are active in advanced cervical cancer. SKYSCRAPER-04 (NCT04300647) explored the clinical activity of Tiragolumab (T, anti-TIGIT) plus atezolizumab (A, anti-PD-L1) dual blockade (T+A) in patients (pts) with PD-L1+ cervical cancer. This study aimed to evaluate the histological, transcriptomic and genomic TME biomarkers associated with both immune checkpoint blockade (ICB: combined A and A+T arms) and predictive of T clinical outcome. Methods: FFPE tumor biopsies were collected from patients with recurrent/persistent PD-L1+ cervical cancer (n=171). Samples were tested for PD-L1 (high TAP ≥10% vs low TAP 5-9%), stromal tumor infiltrating lymphocytes (sTIL by H 26% of pts) had higher ORR for ICB and numerically longer PFS and OS than TMB low (10 mut/Mb). Mutations (mut) of activated PTEN/PIK3CA/AKT pathway was the most prevalent feature (52%) and pts with PIK3CA-mut had higher ICB ORR, PFS and OS. Conclusions: This exploratory analysis suggests that increased tumor immunity and mutation burden (TMB and PIK3CA-mut) correlates with improved ICB clinical outcomes. No biomarkers were clearly associated with tiragolumab outcome. These results are hypothesis generating and should be confirmed in an independent dataset. Citation Format: Venkatesh Krishnan, Ching-Wei Chang, Elyssa Bader, Ritu Salani, Bradley J. Monk, Yong-Man Kim, Sharad Ghamande, Shaundra L. Hall, Domenica Lorusso, Lisa Barraclough, Lucy Gilbert, Adrián Guzmán Ramírez, Chien-Hsing Lu, Dominique Berton, Nicoletta Colombo, Marcela Castro, Yvonne G. Lin, Mary McCormack, Luciana Molinero. Tumor microenvironment (TME) biomarkers of TIGIT and PD-L1 immune checkpoint blockade in cervical cancer: An exploratory biomarker analysis from SKYSCRAPER-04 (SKY04) study abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 5179.