Phase I/II study to evaluate consolidative hypofractionated radiation therapy for boosting the residual primary disease in combination with durvalumab after definitive chemoradiation therapy for stage III non-small cell lung cancer (NSCLC): study protocol for a prospective trial.

Abstract

Recent advancements in the management of non-small cell lung cancer (NSCLC) have confirmed the utility of adding adjuvant immunotherapy to concurrent chemoradiotherapy in stage III disease but intrathoracic progression remains at high rate. Additional studies have sought to investigate the synergistic relationship of immunotherapy and radiation therapy (RT). The goal of this study is to evaluate the safety and efficacy of combining consolidative hypofractionated radiation therapy (hfRT) using stereotactic body radiotherapy (SBRT) technique for boosting the residual primary lung cancer with adjuvant anti-programmed death-ligand 1 (PD-L1) therapy concurrently after completion of definitive chemoradiation therapy (dCRT) in the rates of tumor control locoregionally and distantly. Eligible subjects with stage III NSCLC must have gross residual tumor that is smaller than 5.0 cm in maximal dimension following dCRT. Consolidative hfRT will be delivered 1 to 2 months after finishing dCRT and concurrently with adjuvant anti-PD-L1 therapy using durvalumab. Consolidative hfRT will start from 6.5 Gy ×2 fractions and dose escalate to 10 Gy ×2 fractions in a 3+3 design. At the final determined consolidative hfRT dose level, a total of 32 subjects with pathologically documented stage III NSCLC treated with two or more cycles of platinum-based doublet chemotherapy concurrently with RT will be enrolled for data analyses. We hypothesize that the use of consolidative hfRT directed to the residual primary lung tumor in combination with adjuvant anti-PD-L1 therapy will provide additional immunostimulation and therefore improved locoregional and distant control when compared to either modality used independently. Clinicaltrials.gov: NCT04748419.