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Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760)
INTRODUCTION: S1400F is a non-match substudy of Lung Cancer Master Protocol (Lung-MAP) evaluating the immunotherapy combination of durvalumab and tremelimumab to overcome resistance to anti-programmed death ligand 1 (PD-(L)1) therapy in patients with advanced squamous lung carcinoma (sq non-small-ce...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386207/ https://www.ncbi.nlm.nih.gov/pubmed/34429332 http://dx.doi.org/10.1136/jitc-2021-002973 |
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author | Leighl, Natasha B Redman, Mary W Rizvi, Naiyer Hirsch, Fred R Mack, Philip C Schwartz, Lawrence H Wade, James L Irvin, William J Reddy, Sreekanth C Crawford, Jeffrey Bradley, Jeffrey D Stinchcombe, Thomas E Ramalingam, Suresh S Miao, Jieling Minichiello, Katherine Herbst, Roy S Papadimitrakopoulou, Vassiliki A Kelly, Karen Gandara, David R |
author_facet | Leighl, Natasha B Redman, Mary W Rizvi, Naiyer Hirsch, Fred R Mack, Philip C Schwartz, Lawrence H Wade, James L Irvin, William J Reddy, Sreekanth C Crawford, Jeffrey Bradley, Jeffrey D Stinchcombe, Thomas E Ramalingam, Suresh S Miao, Jieling Minichiello, Katherine Herbst, Roy S Papadimitrakopoulou, Vassiliki A Kelly, Karen Gandara, David R |
author_sort | Leighl, Natasha B |
collection | PubMed |
description | INTRODUCTION: S1400F is a non-match substudy of Lung Cancer Master Protocol (Lung-MAP) evaluating the immunotherapy combination of durvalumab and tremelimumab to overcome resistance to anti-programmed death ligand 1 (PD-(L)1) therapy in patients with advanced squamous lung carcinoma (sq non-small-cell lung cancer (NSCLC)). METHODS: Patients with previously treated sqNSCLC with disease progression after anti-PD-(L)1 monotherapy, who did not qualify for any active molecularly targeted Lung-MAP substudies, were eligible. Patients received tremelimumab 75 mg plus durvalumab 1500 mg once every 28 days for four cycles then durvalumab alone every 28 days until disease progression. The primary endpoint was the objective response rate (RECIST V.1.1). Primary and acquired resistance cohorts, defined as disease progression within 24 weeks versus ≥24 weeks of starting prior anti-PD-(L)1 therapy, were analyzed separately and an interim analysis for futility was planned after 20 patients in each cohort were evaluable for response. RESULTS: A total of 58 eligible patients received drug, 28 with primary resistance and 30 with acquired resistance to anti-PD-(L)1 monotherapy. Grade ≥3 adverse events at least possibly related to treatment were seen in 20 (34%) patients. The response rate in the primary resistance cohort was 7% (95% CI 0% to 17%), with one complete and one partial response. No responses were seen in the acquired resistance cohort. In the primary and resistance cohorts the median progression-free survival was 2.0 months (95% CI 1.6 to 3.0) and 2.1 months (95% CI 1.6 to 3.2), respectively, and overall survival was 7.7 months (95% CI 4.0 to 12.0) and 7.6 months (95% CI 5.3 to 10.2), respectively. CONCLUSION: Durvalumab plus tremelimumab had minimal activity in patients with advanced sqNSCLC progressing on prior anti-PD-1 therapy. Trial registration number NCT03373760. |
format | Online Article Text |
id | pubmed-8386207 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-83862072021-09-09 Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760) Leighl, Natasha B Redman, Mary W Rizvi, Naiyer Hirsch, Fred R Mack, Philip C Schwartz, Lawrence H Wade, James L Irvin, William J Reddy, Sreekanth C Crawford, Jeffrey Bradley, Jeffrey D Stinchcombe, Thomas E Ramalingam, Suresh S Miao, Jieling Minichiello, Katherine Herbst, Roy S Papadimitrakopoulou, Vassiliki A Kelly, Karen Gandara, David R J Immunother Cancer Clinical/Translational Cancer Immunotherapy INTRODUCTION: S1400F is a non-match substudy of Lung Cancer Master Protocol (Lung-MAP) evaluating the immunotherapy combination of durvalumab and tremelimumab to overcome resistance to anti-programmed death ligand 1 (PD-(L)1) therapy in patients with advanced squamous lung carcinoma (sq non-small-cell lung cancer (NSCLC)). METHODS: Patients with previously treated sqNSCLC with disease progression after anti-PD-(L)1 monotherapy, who did not qualify for any active molecularly targeted Lung-MAP substudies, were eligible. Patients received tremelimumab 75 mg plus durvalumab 1500 mg once every 28 days for four cycles then durvalumab alone every 28 days until disease progression. The primary endpoint was the objective response rate (RECIST V.1.1). Primary and acquired resistance cohorts, defined as disease progression within 24 weeks versus ≥24 weeks of starting prior anti-PD-(L)1 therapy, were analyzed separately and an interim analysis for futility was planned after 20 patients in each cohort were evaluable for response. RESULTS: A total of 58 eligible patients received drug, 28 with primary resistance and 30 with acquired resistance to anti-PD-(L)1 monotherapy. Grade ≥3 adverse events at least possibly related to treatment were seen in 20 (34%) patients. The response rate in the primary resistance cohort was 7% (95% CI 0% to 17%), with one complete and one partial response. No responses were seen in the acquired resistance cohort. In the primary and resistance cohorts the median progression-free survival was 2.0 months (95% CI 1.6 to 3.0) and 2.1 months (95% CI 1.6 to 3.2), respectively, and overall survival was 7.7 months (95% CI 4.0 to 12.0) and 7.6 months (95% CI 5.3 to 10.2), respectively. CONCLUSION: Durvalumab plus tremelimumab had minimal activity in patients with advanced sqNSCLC progressing on prior anti-PD-1 therapy. Trial registration number NCT03373760. BMJ Publishing Group 2021-08-24 /pmc/articles/PMC8386207/ /pubmed/34429332 http://dx.doi.org/10.1136/jitc-2021-002973 Text en © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Clinical/Translational Cancer Immunotherapy Leighl, Natasha B Redman, Mary W Rizvi, Naiyer Hirsch, Fred R Mack, Philip C Schwartz, Lawrence H Wade, James L Irvin, William J Reddy, Sreekanth C Crawford, Jeffrey Bradley, Jeffrey D Stinchcombe, Thomas E Ramalingam, Suresh S Miao, Jieling Minichiello, Katherine Herbst, Roy S Papadimitrakopoulou, Vassiliki A Kelly, Karen Gandara, David R Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760) |
title | Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760) |
title_full | Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760) |
title_fullStr | Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760) |
title_full_unstemmed | Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760) |
title_short | Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760) |
title_sort | phase ii study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-pd-1/pd-l1 resistant stage iv squamous cell lung cancer (lung-map substudy s1400f, nct03373760) |
topic | Clinical/Translational Cancer Immunotherapy |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386207/ https://www.ncbi.nlm.nih.gov/pubmed/34429332 http://dx.doi.org/10.1136/jitc-2021-002973 |
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