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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 (ClinicalTrials.gov 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 iaslc.org.


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