Evolution of peripheral and tumor immune parameters as biomarkers of differential sequencing of immune checkpoint blockade and chemoradiotherapy in locally advanced cervical cancer: An NRG Oncology/GOG Study

Several clinical trials have evaluated concurrent immune checkpoint blockade (ICB) and chemoradiation (CRT) in locally advanced cervical cancer (LACC). However, optimal ICB-CRT sequencing is unknown, as CRT concurrent with ICB carries the potential to kill the proliferating T cells in tumor-draining lymph nodes (LN) and worsen outcomes. To address this critical knowledge gap, we performed NRG-GY017, a randomized trial of the anti-PD-L1 antibody atezolizumab before and concurrent (Arm A) or concurrent with CRT (Arm B) in patients with high-risk pelvic or para-aortic LN-positive LACC. Here we report on the pre-specified integral (T-cell receptor [TCR] clonality), integrated (PD-L1 expression), and several exploratory biomarkers as early pharmacodynamic indicators of the immune response.