Canakinumab with chemoradiation and durvalumab consolidation in unresectable stage III non-small cell lung cancer: the phase I/II CHORUS trial.

Authors

Narek Shaverdian, Michael Offin, Nicolas Toumbacaris, Jasme Lee, Karmelina Charalambous, Daphna Y Gelblum, Fernando C Santini, Annemarie F Shepherd, Richard Gewanter, Boris Mueller, Jacob Y Shin, Abraham J Wu, Charles B Simone, Andreas Rimner, Nancy Y Lee, Michelle S Ginsberg, Helena Yu, Bobby Daly, Mark G Kris, Isabel Preeshagul, Paul Paik, Juliana Eng, Afsheen Iqbal, Kenneth Ng, Michael Berger, Ronak Shah, Ronglai Shen, Phillip Wong, Zhigang Zhang, Daniel R Gomez, Jamie E Chaft

Published in

Nature communications. Volume 17. Issue 1. Sep 07, 2026. Epub Sep 07, 2026.

Abstract

CHORUS (NCT04905316) was an open-label, non-randomized, single-arm phase I/II trial of the anti-IL-1beta monoclonal antibody canakinumab given with concurrent chemoradiotherapy and continued with anti-PD-L1 durvalumab consolidation in unresectable stage III non-small cell lung cancer. The primary endpoint was 24-month progression-free survival (PFS) from radiotherapy initiation; secondary endpoints included overall survival, objective response rate, and safety. Forty-one patients were enrolled, 37 received canakinumab, and 32 comprised the prespecified efficacy population. At a median follow-up of 25 months, 24-month PFS was 67% (95% confidence interval, 52-88); the lower bound of the prespecified one-sided 90% confidence interval was 56.5%, exceeding the 46% historical benchmark, and the primary endpoint was met. Twelve- and 24-month overall survival were 93% and 73%, respectively, and the confirmed objective response rate was 81%. Canakinumab-related grade 3-4 events included neutropenia (n = 5), febrile neutropenia (n = 1), lymphopenia (n = 1), lung infection (n = 1), fatigue (n = 1), and hypertension (n = 1); no canakinumab-related deaths occurred. Pneumonitis of any attribution occurred in 9 of 37 patients (24%; grade 2, n = 7; grade 3, n = 2). Peripheral immune cell profiling showed attenuated expansion of myeloid-derived suppressor cells and CTLA-4-expressing CD8 + T-cell subsets among responders. Circulating tumor DNA cleared by week 6 in 20 of 30 evaluable patients (66%). These findings support randomized evaluation of interleukin-1β blockade in this setting.

PMID:
42844242
Bibliographic data and abstract were imported from PubMed on 08 Oct 2026.

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