Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial

Autor: Tina Cascone, Cheuk H. Leung, Annikka Weissferdt, Apar Pataer, Brett W. Carter, Myrna C. B. Godoy, Hope Feldman, William N. William, Yuanxin Xi, Sreyashi Basu, Jing Jing Sun, Shalini S. Yadav, Frank R. Rojas Alvarez, Younghee Lee, Aditya K. Mishra, Lili Chen, Monika Pradhan, Haiping Guo, Ansam Sinjab, Nicolas Zhou, Marcelo V. Negrao, Xiuning Le, Carl M. Gay, Anne S. Tsao, Lauren Averett Byers, Mehmet Altan, Bonnie S. Glisson, Frank V. Fossella, Yasir Y. Elamin, George Blumenschein, Jianjun Zhang, Ferdinandos Skoulidis, Jia Wu, Reza J. Mehran, David C. Rice, Garrett L. Walsh, Wayne L. Hofstetter, Ravi Rajaram, Mara B. Antonoff, Junya Fujimoto, Luisa M. Solis, Edwin R. Parra, Cara Haymaker, Ignacio I. Wistuba, Stephen G. Swisher, Ara A. Vaporciyan, Heather Y. Lin, Jing Wang, Don L. Gibbons, J. Jack Lee, Nadim J. Ajami, Jennifer A. Wargo, James P. Allison, Padmanee Sharma, Humam Kadara, John V. Heymach, Boris Sepesi
Rok vydání: 2023
Předmět:
Zdroj: Nature Medicine. 29:593-604
ISSN: 1546-170X
1078-8956
Popis: Neoadjuvant ipilimumab + nivolumab (Ipi+Nivo) and nivolumab + chemotherapy (Nivo+CT) induce greater pathologic response rates than CT alone in patients with operable non-small cell lung cancer (NSCLC). The impact of adding ipilimumab to neoadjuvant Nivo+CT is unknown. Here we report the results and correlates of two arms of the phase 2 platform NEOSTAR trial testing neoadjuvant Nivo+CT and Ipi+Nivo+CT with major pathologic response (MPR) as the primary endpoint. MPR rates were 32.1% (7/22, 80% confidence interval (CI) 18.7–43.1%) in the Nivo+CT arm and 50% (11/22, 80% CI 34.6–61.1%) in the Ipi+Nivo+CT arm; the primary endpoint was met in both arms. In patients without known tumor EGFR/ALK alterations, MPR rates were 41.2% (7/17) and 62.5% (10/16) in the Nivo+CT and Ipi+Nivo+CT groups, respectively. No new safety signals were observed in either arm. Single-cell sequencing and multi-platform immune profiling (exploratory endpoints) underscored immune cell populations and phenotypes, including effector memory CD8+ T, B and myeloid cells and markers of tertiary lymphoid structures, that were preferentially increased in the Ipi+Nivo+CT cohort. Baseline fecal microbiota in patients with MPR were enriched with beneficial taxa, such as Akkermansia, and displayed reduced abundance of pro-inflammatory and pathogenic microbes. Neoadjuvant Ipi+Nivo+CT enhances pathologic responses and warrants further study in operable NSCLC. (ClinicalTrials.gov registration: NCT03158129.)
Databáze: OpenAIRE
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