Data from Response-Adaptive Surgical Timing in Neoadjuvant Immunotherapy Demonstrates Enhanced Pathologic Treatment Response in Head and Neck Squamous Cell Carcinoma

• DOI: 10.1158/1078-0432.c.7655002
• Publication Date: 2025-02-03T08:22:45Z
• Authors: Eric V. Mastrolon...; Kathryn L. Nunes; Pablo Llerena; Anastasia Nikitina; Anastasia Sobol; E. Reilly Scott; Madalina Tuluc; Christopher J.H. ...; Jessica Scher; Sruti Tekumalla; Derek Mann; Camilo Henao; Victor Jegede; Stacey Gargano; Larry A. Harshyne; Angela Alnemri; Andrey Tyshevich; Vladimir Kushnarev; Madison Chasse; Danielle Sookiasian; Rita Axelrod; Tingting Zhan; Benjamin E. Leiby; Matthew Old; Nolan Seim; My G. Mahoney; Ubaldo Martinez-O...; David M. Cognetti; Joseph M. Curry; George Prendergast; Athanassios Argiris; Andrew P. South; Alban J. Linnenbach; Jennifer M. Johnson; Adam J. Luginbuhl
• Keywords: Complete response

<div>AbstractPurpose:<p>We evaluated whether indoleamine 2,3-dioxygenase (IDO1) inhibitor (IDOi) BMS986205 + PD-1 nivolumab enhanced T-cell activity and augmented immune-mediated antitumor responses in untreated, resectable head neck squamous cell carcinoma (HNSCC). We employed response-adaptive surgical timing to identify responders immunotherapy enhance their response.</p>Patients Methods:<p>Patients with HNSCC were 3:1 randomized receive or without orally daily (NCT03854032). In the combination arm, was initiated 7 days prior nivolumab. Patients stratified by human papillomavirus (HPV) status. Response-adaptive involved response assessment radiographic criteria 4 weeks after treatment both arms. Nonresponders underwent resection, whereas received more of therapy before surgery. Biomarker analysis utilized pathologic (pTR) RNA sequencing.</p>Results:<p>Forty-two patients enrolled, addition IDOi did not result greater rate (<i>P</i> = 0.909). Treatment well tolerated, only 2 (5%) experiencing grade 3 immune-related adverse events. The rates pTR high baseline IDO1 expression < 0.05). demonstrated reliability differentiating versus nonresponders 0.009). A pretreatment NK signature, PD-L1 status, IFN-γ HPV<sup>−</sup> cohort correlated response. HPV<sup>+</sup> found B-cell cancer-associated fibroblast signatures predictive response/nonresponse.</p>Conclusions:<p>Response-adaptive samples, indicating a need for identifying targeting resistant nodes immunotherapy. HPV status–dependent predicting warrant further study.</p></div>