Neoadjuvant or concurrent atezolizumab with chemoradiation for locally advanced cervical cancer: a randomized phase I trial

Jyoti Mayadev (), Dmitriy Zamarin, Wei Deng, Heather A. Lankes, Giulio Pesci, Hayeon Kim, Junzo P. Chino, Barbara Banbury, Ned Sherry, Elad Sharon, Sharad A. Ghamande, Catherine Ferguson, Loren Mell, Laura Holman, Cara Mathews, David O’Malley, Alexander Olawaiye, Elizabeth Hopp, Charles Leath, Larry Copeland, Robert Mannel, Roisin O’Cearbhaill, Carol Aghajanian and Russell J. Schilder
Additional contact information
Jyoti Mayadev: University of California San Diego
Dmitriy Zamarin: Icahn School of Medicine at Mount Sinai
Wei Deng: NRG Oncology Statistics & Data Center
Heather A. Lankes: NRG OncologyOperations Center-Philadelphia East
Giulio Pesci: Memorial Sloan-Kettering Cancer Center
Hayeon Kim: UPMC Hillman Cancer Center
Junzo P. Chino: Duke University
Barbara Banbury: Adaptive Biotechnologies Corp
Ned Sherry: Adaptive Biotechnologies Corp
Elad Sharon: Dana Faber Cancer Institute
Sharad A. Ghamande: Augusta University Medical College of Georgia
Catherine Ferguson: Augusta University Medical College of Georgia
Loren Mell: University of California San Diego
Laura Holman: University of Oklahoma Health Sciences Center
Cara Mathews: Women & Infants Hospital
David O’Malley: The Ohio State University Wexner Medical Center Columbus
Alexander Olawaiye: University of Pittsburgh Medical Center
Elizabeth Hopp: Medical College of Wisconsin
Charles Leath: University of Alabama
Larry Copeland: The Ohio State University Wexner Medical Center Columbus
Robert Mannel: University of Oklahoma Health Sciences Center
Roisin O’Cearbhaill: Memorial Sloan-Kettering Cancer Center
Carol Aghajanian: Memorial Sloan-Kettering Cancer Center
Russell J. Schilder: Jefferson University Sidney Kimmel Medical College

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: Abstract Combined immune checkpoint blockade (ICB) and chemoradiation (CRT) is approved in patients with locally advanced cervical cancer (LACC) but optimal sequencing of CRT and ICB is unknown. NRG-GY017 (NCT03738228) was a randomized phase I trial of atezolizumab (anti-PD-L1) neoadjuvant and concurrent with CRT (Arm A) vs. concurrent with CRT (Arm B) in patients with high-risk node-positive LACC. The primary endpoint was the fraction of expanded tumor-associated T-cell receptor (TCR) clones in blood at day 21 as a surrogate measure of anti-tumor immune response. Secondary objectives were safety and feasibility, 2-year disease-free survival (DFS), and predictive value of PD-L1 expression. Forty patients were randomized, 36 received treatment, and 25 were evaluable for the primary endpoint. After cycle 1, there was peripheral expansion of higher proportion of tumor-associated TCR clones in Arm A than in Arm B (p = 0.0025) that remained higher at day 21, meeting the pre-specified endpoint on two-sample T-test (p = 0.052), but not on sensitivity analysis by Wilcoxon test (p = 0.13). At the median follow up of 25.8 months, 2-year DFS was 76% in Arm A and 56% in Arm B (p = 0.28). There were no new safety signals. In conclusion, neoadjuvant ICB prior to CRT was safe and was associated with immunologically and clinically favorable outcomes, warranting larger confirmatory studies.

Date: 2025
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DOI: 10.1038/s41467-024-55200-2

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