A Phase III Study of Induction Pembrolizumab and Chemotherapy Followed by Chemoradiation and Pembrolizumab vs Chemoradiation and Pembrolizumab Both Followed by Pembrolizumab for High Risk Locally Advanced Cervical Cancer
Primary Objective To determine whether induction IO and chemotherapy prior to CCRT+IO improves progression-free survival (PFS) compared to CCRT+IO alone. Secondary Objectives To assess whether induction IO and chemotherapy prior to CCRT+IO improves the overall survival (OS) compared to CCRT+IO alone. To determine the nature and degree of toxicity of induction IO and chemotherapy prior to CCRT + IO as compared to concurrent CCRT+IO as assessed by CTCAE v5.0. To determine the impact on CCRT start, CCRT completion time, and number of cycles of cisplatin administered; with induction IO and chemotherapy prior to CCRT+IO arm as compared to CCRT+IO. To assess the association between allostatic load and PFS/OS. To assess the predictive value of the integrated biomarker: PD-L1 expression at baseline for progression free survival. To assess the prognostic and predictive value of the integrated biomarker: ctDNA at baseline and at 3 months post RT for progression free survival. To explore radiotherapy quality pretreatment scores conducted by expert review with assistance from AI models and correlation with outcomes. Exploratory Objectives To assess the evolution of T cell receptor (TCR) repertoire on treatment and its correlation with clinical outcomes. To identify pre-treatment tumor microenvironment biomarkers predictive of outcomes.