Study

NRG-GY037: 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: I. To determine whether induction immunotherapy (IO) and chemotherapy prior to concurrent chemoradiation therapy (CCRT) + IO improves progression-free survival (PFS) compared to CCRT+IO alone. SECONDARY OBJECTIVES: I. To assess whether induction IO and chemotherapy prior to CCRT+IO improves the overall survival (OS) compared to CCRT+IO alone. II. 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 Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. III. 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. IV. To assess the association between allostatic load and PFS/OS. V. To assess the predictive value of the integrated biomarker: PD-L1 expression at baseline for progression free survival. VI. To assess the prognostic and predictive value of the integrated biomarker: circulating tumor deoxyribonucleic acid (ctDNA) at baseline and at 3 months post radiation therapy (RT) for progression free survival. VII. To explore radiotherapy quality pretreatment scores conducted by expert review with assistance from artificial intelligence (AI) models and correlation with outcomes. EXPLORATORY OBJECTIVES: I. To assess the evolution of T cell receptor (TCR) repertoire on treatment and its correlation with clinical outcomes. II. To identify pre-treatment tumor microenvironment biomarkers predictive of outcomes.

Why this Research Matters

This phase III trial compares the addition of induction chemotherapy, with carboplatin, paclitaxel and pembrolizumab, to chemotherapy and radiation, with cisplatin and pembrolizumab followed by pembrolizumab maintenance for the treatment of patients with cervical cancer that has spread to nearby tissue or lymph nodes (locally advanced). Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Adding induction chemotherapy to the usual treatment of chemotherapy and radiation followed by maintenance may be more effective in treating patients with high risk, locally advanced cervical cancer.

Who can Participate

Adult

Detailed eligibility criteria is available on ClinicalTrials.gov. These requirements will be discussed with your doctor and/or study representative. ClinicalTrials.gov to learn more about this study. https://clinicaltrials.gov/study/NCT07061977?term=NCT07061977&rank=1