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David S. Ettinger, MD, FACP, FCCP


WCLC 2022: Biomarker-Directed Study of Treatment Options in NSCLC After Immunotherapy

By: Jenna Carter, PhD
Posted: Thursday, August 11, 2022

A study presented at the International Association for the Study of Lung Cancer (IASLC) 2022 World Conference on Lung Cancer (WCLC; Abstract OA15.05) highlighted the efficacy, safety, and tolerability of alternative treatment combinations to overcome resistance to PD-L1 blockade in patients with non–small-cell lung cancer (NSCLC). John Heymach, MD, PhD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues used data from the HUDSON multiarm umbrella trial ( identifier NCT03334617) to assess treatment and found that the combination of the monoclonal antibody durvalumab plus the ATR inhibitor ceralasertib demonstrated activity with a tolerable safety profile.

“The study evaluates…multiple treatment combinations tailored by molecular alteration, with the goal of overcoming resistance to [PD-L1] blockade. Here, we present mature efficacy and safety results for the initial combinations—durvalumab plus olaparib (PARP inhibitor; Module 1), danvatirsen (STAT3 inhibitor; Module 2), ceralasertib (Module 3), and oleclumab (anti-CD73 antibody; Module 5),” stated Dr. Heymach and colleagues.

A total of 255 patients were enrolled in this study between January 2018 and April 2021. Based on tumor molecular profiles, patients were separated into either a biomarker-matched group (group A) or a biomarker-nonmatched cohort (group B). Patients in group B were then further subdivided by primary or acquired resistance to prior anti–PD-L1 treatment. The primary endpoint was overall response rate, whereas the secondary endpoints included progression-free and overall survival.

Findings revealed an overall response rate and 12-week/24-week disease control rates were highest with durvalumab plus ceralasertib, and efficacy appeared greatest in the biomarker-matched cohort. Additionally, patient-reported treatment-related adverse events of grade 3 or higher were lower with durvalumab plus ceralasertib or oleclumab than with the other regimens.

Disclosure: For full disclosures of the study authors, visit

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