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.

Background

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.

Methods

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.

Discussion

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.

Registration

Clinicaltrials.gov: NCT04748419.

Informations de copyright

2024 Journal of Thoracic Disease. All rights reserved.

Déclaration de conflit d'intérêts

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-304/coif). C.Z. received grand funding from AstraZeneca, Inc., clinical trial research funding from BioMiMetix, and travel support from GTMedical Technologies. C.Z. reports a US Provisional patent (63/164,215) issued which is unrelated to the current study. A.K.G. reports Grants to his institution from Veterans Health Administration Office of Research and Development, Merck, TAB Biosciences, NEKTAR Therapeutics, Mirati Therapeutics, IOVANCE Therapeutics, Apexigen; Royalties from Oxford University Press; Consulting fees from AstraZeneca, Flagship Biosciences, G1 Therapeutics, Jazz Pharmaceuticals, Cardinal Health, Mirati Therapeutics, Beigene Ltd., Sanofi Genzyme, Blueprint Medicines, Regeneron Pharmaceuticals; Honoraria for lectures from MedLearning Group and Plexus Communications; DSMB for YmAbs Therapeutics; Leadership roles in Academic and Community Cancer Research United (ACCRU) and A Breath of Hope for Lung Cancer (ABOHLC); Receipt of drugs to the institution from Takeda Pharmaceuticals and Chimerx. C.W. reports funding from Chi Zhang’s grant (PI Astra Zeneca Pharmaceuticals IIT Grant; UNMC project number MEDI4736). The other authors have no conflicts of interest to declare.