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Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial
Immunotherapy combined with antiangiogenic targeted therapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for refractory recurrent/metastatic nasopharyngeal carcinoma (RM-NPC). We conducted a phase 2 trial to evaluate the safety and activity of camrelizuma...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10425437/ https://www.ncbi.nlm.nih.gov/pubmed/37580352 http://dx.doi.org/10.1038/s41467-023-40402-x |
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author | Yuan, Li Jia, Guo-Dong Lv, Xiao-Fei Xie, Si-Yi Guo, Shan-Shan Lin, Da-Feng Liu, Li-Ting Luo, Dong-Hua Li, Yi-Fu Deng, Shen-Wen Guo, Ling Zeng, Mu-Sheng Cai, Xiu-Yu Liu, Sai-Lan Sun, Xue-Song Li, Xiao-Yun Li, Su-Chen Chen, Qiu-Yan Tang, Lin-Quan Mai, Hai-Qiang |
author_facet | Yuan, Li Jia, Guo-Dong Lv, Xiao-Fei Xie, Si-Yi Guo, Shan-Shan Lin, Da-Feng Liu, Li-Ting Luo, Dong-Hua Li, Yi-Fu Deng, Shen-Wen Guo, Ling Zeng, Mu-Sheng Cai, Xiu-Yu Liu, Sai-Lan Sun, Xue-Song Li, Xiao-Yun Li, Su-Chen Chen, Qiu-Yan Tang, Lin-Quan Mai, Hai-Qiang |
author_sort | Yuan, Li |
collection | PubMed |
description | Immunotherapy combined with antiangiogenic targeted therapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for refractory recurrent/metastatic nasopharyngeal carcinoma (RM-NPC). We conducted a phase 2 trial to evaluate the safety and activity of camrelizumab plus apatinib in platinum-resistant (cohort 1, NCT04547088) and PD-1 inhibitor resistant NPC (cohort 2, NCT04548271). Here we report on the primary outcome of objective response rate (ORR) and secondary endpoints of safety, duration of response, disease control rate, progression-free survival, and overall survival. The primary endpoint of ORR was met for cohort 1 (65%, 95% CI, 49.6–80.4, n = 40) and cohort 2 (34.3%; 95% CI, 17.0–51.8, n = 32). Grade ≥ 3 treatment-related adverse events (TRAE) were reported in 47 (65.3%) of 72 patients. Results of our predefined exploratory investigation of predictive biomarkers show: B cell markers are the most differentially expressed genes in the tumors of responders versus non-responders in cohort 1 and that tertiary lymphoid structure is associated with higher ORR; Angiogenesis gene expression signatures are strongly associated with ORR in cohort 2. Camrelizumab plus apatinib combination effectiveness is associated with high expression of PD-L1, VEGF Receptor 2 and B-cell-related genes signatures. Camrelizumab plus apatinib shows promising efficacy with a measurable safety profile in RM-NPC patients. |
format | Online Article Text |
id | pubmed-10425437 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-104254372023-08-16 Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial Yuan, Li Jia, Guo-Dong Lv, Xiao-Fei Xie, Si-Yi Guo, Shan-Shan Lin, Da-Feng Liu, Li-Ting Luo, Dong-Hua Li, Yi-Fu Deng, Shen-Wen Guo, Ling Zeng, Mu-Sheng Cai, Xiu-Yu Liu, Sai-Lan Sun, Xue-Song Li, Xiao-Yun Li, Su-Chen Chen, Qiu-Yan Tang, Lin-Quan Mai, Hai-Qiang Nat Commun Article Immunotherapy combined with antiangiogenic targeted therapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for refractory recurrent/metastatic nasopharyngeal carcinoma (RM-NPC). We conducted a phase 2 trial to evaluate the safety and activity of camrelizumab plus apatinib in platinum-resistant (cohort 1, NCT04547088) and PD-1 inhibitor resistant NPC (cohort 2, NCT04548271). Here we report on the primary outcome of objective response rate (ORR) and secondary endpoints of safety, duration of response, disease control rate, progression-free survival, and overall survival. The primary endpoint of ORR was met for cohort 1 (65%, 95% CI, 49.6–80.4, n = 40) and cohort 2 (34.3%; 95% CI, 17.0–51.8, n = 32). Grade ≥ 3 treatment-related adverse events (TRAE) were reported in 47 (65.3%) of 72 patients. Results of our predefined exploratory investigation of predictive biomarkers show: B cell markers are the most differentially expressed genes in the tumors of responders versus non-responders in cohort 1 and that tertiary lymphoid structure is associated with higher ORR; Angiogenesis gene expression signatures are strongly associated with ORR in cohort 2. Camrelizumab plus apatinib combination effectiveness is associated with high expression of PD-L1, VEGF Receptor 2 and B-cell-related genes signatures. Camrelizumab plus apatinib shows promising efficacy with a measurable safety profile in RM-NPC patients. Nature Publishing Group UK 2023-08-14 /pmc/articles/PMC10425437/ /pubmed/37580352 http://dx.doi.org/10.1038/s41467-023-40402-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Yuan, Li Jia, Guo-Dong Lv, Xiao-Fei Xie, Si-Yi Guo, Shan-Shan Lin, Da-Feng Liu, Li-Ting Luo, Dong-Hua Li, Yi-Fu Deng, Shen-Wen Guo, Ling Zeng, Mu-Sheng Cai, Xiu-Yu Liu, Sai-Lan Sun, Xue-Song Li, Xiao-Yun Li, Su-Chen Chen, Qiu-Yan Tang, Lin-Quan Mai, Hai-Qiang Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial |
title | Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial |
title_full | Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial |
title_fullStr | Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial |
title_full_unstemmed | Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial |
title_short | Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial |
title_sort | camrelizumab combined with apatinib in patients with first-line platinum-resistant or pd-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10425437/ https://www.ncbi.nlm.nih.gov/pubmed/37580352 http://dx.doi.org/10.1038/s41467-023-40402-x |
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