Neoadjuvant or concurrent atezolizumab with chemoradiation for locally advanced cervical cancer: a randomized phase I trial
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 concu...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55200-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850119428333633536 |
|---|---|
| author | 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 Russell J. Schilder |
| author_facet | 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 Russell J. Schilder |
| author_sort | Jyoti Mayadev |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a759a9d1a47644199691b4dde0ea0cb8 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-a759a9d1a47644199691b4dde0ea0cb82025-08-20T02:35:37ZengNature PortfolioNature Communications2041-17232025-01-0116111010.1038/s41467-024-55200-2Neoadjuvant or concurrent atezolizumab with chemoradiation for locally advanced cervical cancer: a randomized phase I trialJyoti Mayadev0Dmitriy Zamarin1Wei Deng2Heather A. Lankes3Giulio Pesci4Hayeon Kim5Junzo P. Chino6Barbara Banbury7Ned Sherry8Elad Sharon9Sharad A. Ghamande10Catherine Ferguson11Loren Mell12Laura Holman13Cara Mathews14David O’Malley15Alexander Olawaiye16Elizabeth Hopp17Charles Leath18Larry Copeland19Robert Mannel20Roisin O’Cearbhaill21Carol Aghajanian22Russell J. Schilder23University of California San DiegoIcahn School of Medicine at Mount SinaiNRG Oncology Statistics & Data CenterNRG OncologyOperations Center-Philadelphia EastMemorial Sloan-Kettering Cancer CenterUPMC Hillman Cancer CenterDuke UniversityAdaptive Biotechnologies CorpAdaptive Biotechnologies CorpDana Faber Cancer InstituteAugusta University Medical College of GeorgiaAugusta University Medical College of GeorgiaUniversity of California San DiegoUniversity of Oklahoma Health Sciences CenterWomen & Infants HospitalThe Ohio State University Wexner Medical Center ColumbusUniversity of Pittsburgh Medical CenterMedical College of WisconsinUniversity of AlabamaThe Ohio State University Wexner Medical Center ColumbusUniversity of Oklahoma Health Sciences CenterMemorial Sloan-Kettering Cancer CenterMemorial Sloan-Kettering Cancer CenterJefferson University Sidney Kimmel Medical CollegeAbstract 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.https://doi.org/10.1038/s41467-024-55200-2 |
| spellingShingle | 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 Russell J. Schilder Neoadjuvant or concurrent atezolizumab with chemoradiation for locally advanced cervical cancer: a randomized phase I trial Nature Communications |
| title | Neoadjuvant or concurrent atezolizumab with chemoradiation for locally advanced cervical cancer: a randomized phase I trial |
| title_full | Neoadjuvant or concurrent atezolizumab with chemoradiation for locally advanced cervical cancer: a randomized phase I trial |
| title_fullStr | Neoadjuvant or concurrent atezolizumab with chemoradiation for locally advanced cervical cancer: a randomized phase I trial |
| title_full_unstemmed | Neoadjuvant or concurrent atezolizumab with chemoradiation for locally advanced cervical cancer: a randomized phase I trial |
| title_short | Neoadjuvant or concurrent atezolizumab with chemoradiation for locally advanced cervical cancer: a randomized phase I trial |
| title_sort | neoadjuvant or concurrent atezolizumab with chemoradiation for locally advanced cervical cancer a randomized phase i trial |
| url | https://doi.org/10.1038/s41467-024-55200-2 |
| work_keys_str_mv | AT jyotimayadev neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT dmitriyzamarin neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT weideng neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT heatheralankes neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT giuliopesci neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT hayeonkim neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT junzopchino neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT barbarabanbury neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT nedsherry neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT eladsharon neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT sharadaghamande neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT catherineferguson neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT lorenmell neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT lauraholman neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT caramathews neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT davidomalley neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT alexanderolawaiye neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT elizabethhopp neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT charlesleath neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT larrycopeland neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT robertmannel neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT roisinocearbhaill neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT carolaghajanian neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial AT russelljschilder neoadjuvantorconcurrentatezolizumabwithchemoradiationforlocallyadvancedcervicalcancerarandomizedphaseitrial |