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Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial

Medicine and Health

Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial

B. Besse, E. Pons-tostivint, et al.

In a groundbreaking phase 2 umbrella study, researchers, including Benjamin Besse and Patrick M. Forde, have explored innovative combination regimens for advanced non-small cell lung cancer (NSCLC) after failed immunotherapy. The combination of durvalumab with ceralasertib demonstrated remarkable efficacy, with an objective response rate of 13.9% and a median overall survival of 17.4 months. This study unveils promising directions for future investigations into NSCLC treatments.

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Playback language: English
Abstract
This phase 2 umbrella HUDSON study evaluated rational combination regimens for advanced NSCLC following failure of anti-PD-(L)1-containing immunotherapy and platinum-doublet therapy. 268 patients received durvalumab with ceralasertib, olaparib, danvatirsen, or oleclumab. Durvalumab-ceralasertib showed greatest clinical benefit (ORR 13.9% vs 2.6% for other regimens); median PFS was 5.8 months vs 2.7 months; median OS was 17.4 months vs 9.4 months. Benefit was consistent across immunotherapy-refractory subgroups. In ATM-altered patients, ORR was 26.1%. Durvalumab-ceralasertib's safety profile was manageable. Biomarker analyses suggested immune changes reinvigorating antitumor immunity. Durvalumab-ceralasertib is under further investigation.
Publisher
Nature Medicine
Published On
Mar 01, 2024
Authors
Benjamin Besse, Elvire Pons-Tostivint, Keunchil Park, Sylvia Hartl, Patrick M. Forde, Maximilian J. Hochmair, Mark M. Awad, Michael Thomas, Glenwood Goss, Paul Wheatley-Price, Frances A. Shepherd, Marie Florescu, Parneet Cheema, Quincy S. C. Chu, Sang-We Kim, Daniel Morgensztern, Melissa L. Johnson, Sophie Cousin, Dong-Wan Kim, Mor T. Moskovitz, David Vicente, Boaz Aronson, Rosalind Hobson, Helen J. Ambrose, Sajan Khosla, Avinash Reddy, Deanna L. Russell, Mohamed Reda Keddar, James P. Conway, J. Carl Barrett, Emma Dean, Rakesh Kumar, Marlene Dressman, Philip J. Jewsbury, Sonia Iyer, Simon T. Barry, Jan Cosaert, John V. Heymach
Tags
advanced NSCLC
durvalumab
ceralasertib
combination regimens
immunotherapy
clinical benefit
platinum-doublet therapy
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