Study protocol of KeyPemls‐004: A phase 2 study of pembrolizumab in combination with plinabulin and docetaxel in previously treated patients with metastatic non‐small cell lung cancer and progressive disease (PD) after immunotherapy (PD‐1/PD‐L1 inhibitor) alone or in combination with platinum‐doublet chemotherapy
Abstract Introduction Immune checkpoint inhibitor (ICI)‐based treatment regimens have become the standard of care for first‐line treatment of metastatic epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) wild‐type non‐small cell lung cancer (NSCLC). Nevertheless, most patients...
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| Format: | Article |
| Language: | English |
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Wiley
2023-03-01
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| Series: | Thoracic Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/1759-7714.14806 |
| _version_ | 1811154198527475712 |
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| author | Jia Liu Minjiang Chen Xiaoxing Gao Xiaoyan Liu Jing Zhao Ruili Pan Wei Zhong Yan Xu Mengzhao Wang |
| author_facet | Jia Liu Minjiang Chen Xiaoxing Gao Xiaoyan Liu Jing Zhao Ruili Pan Wei Zhong Yan Xu Mengzhao Wang |
| author_sort | Jia Liu |
| collection | DOAJ |
| description | Abstract Introduction Immune checkpoint inhibitor (ICI)‐based treatment regimens have become the standard of care for first‐line treatment of metastatic epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) wild‐type non‐small cell lung cancer (NSCLC). Nevertheless, most patients inevitably develop disease progression, and the mechanisms of resistance to first‐line immunotherapy are not clear. ICIs in combination with agents targeting other pathways may serve as second‐line therapy options. Plinabulin is a selective immunomodulating microtubule‐binding agent which inhibits the polymerization of tubulin monomers, with multiple mechanisms to inhibit tumor growth. Clinical studies have demonstrated preliminary the antitumor efficacy of this agent. Therefore, we hypothesize that a combination of plinabulin with programmed death 1 (PD‐1) inhibitor and docetaxel may result in higher efficacy and fewer side effects leading to better tolerance. Methods In this investigator‐initiated, single‐arm, open‐label, phase II trial, metastatic NSCLC patients who acquired resistance to first‐line immunotherapy‐based therapy will be enrolled. Participants will receive pembrolizumab 200 mg D1, plinabulin 30 mg/m2 D1 and D8, and docetaxel 75 mg/m2 D1 intravenously for a 21‐day cycle. The study intervention will be given until disease progression, intolerable toxicity, informed consent withdrawal or investigator decision. The primary endpoint is investigator‐based objective response rate per Response Evaluation Criteria in Solid Tumors, version 1.1. The secondary endpoints are progression‐free survival, overall survival, duration of response, and safety. Discussion This trial will provide evidence of the benefit and safety of pembrolizumab in combination with plinabulin and docetaxel in metastatic NSCLC patients who have been exposed and developed resistance to first‐line PD‐1/PD‐L1 inhibitor either as monotherapy or in combination with chemotherapy. |
| first_indexed | 2024-04-10T04:11:44Z |
| format | Article |
| id | doaj.art-7044e1192cda46f4b3e23f43c590c731 |
| institution | Directory Open Access Journal |
| issn | 1759-7706 1759-7714 |
| language | English |
| last_indexed | 2024-04-10T04:11:44Z |
| publishDate | 2023-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Thoracic Cancer |
| spelling | doaj.art-7044e1192cda46f4b3e23f43c590c7312023-03-13T02:00:47ZengWileyThoracic Cancer1759-77061759-77142023-03-0114877377810.1111/1759-7714.14806Study protocol of KeyPemls‐004: A phase 2 study of pembrolizumab in combination with plinabulin and docetaxel in previously treated patients with metastatic non‐small cell lung cancer and progressive disease (PD) after immunotherapy (PD‐1/PD‐L1 inhibitor) alone or in combination with platinum‐doublet chemotherapyJia Liu0Minjiang Chen1Xiaoxing Gao2Xiaoyan Liu3Jing Zhao4Ruili Pan5Wei Zhong6Yan Xu7Mengzhao Wang8Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaAbstract Introduction Immune checkpoint inhibitor (ICI)‐based treatment regimens have become the standard of care for first‐line treatment of metastatic epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) wild‐type non‐small cell lung cancer (NSCLC). Nevertheless, most patients inevitably develop disease progression, and the mechanisms of resistance to first‐line immunotherapy are not clear. ICIs in combination with agents targeting other pathways may serve as second‐line therapy options. Plinabulin is a selective immunomodulating microtubule‐binding agent which inhibits the polymerization of tubulin monomers, with multiple mechanisms to inhibit tumor growth. Clinical studies have demonstrated preliminary the antitumor efficacy of this agent. Therefore, we hypothesize that a combination of plinabulin with programmed death 1 (PD‐1) inhibitor and docetaxel may result in higher efficacy and fewer side effects leading to better tolerance. Methods In this investigator‐initiated, single‐arm, open‐label, phase II trial, metastatic NSCLC patients who acquired resistance to first‐line immunotherapy‐based therapy will be enrolled. Participants will receive pembrolizumab 200 mg D1, plinabulin 30 mg/m2 D1 and D8, and docetaxel 75 mg/m2 D1 intravenously for a 21‐day cycle. The study intervention will be given until disease progression, intolerable toxicity, informed consent withdrawal or investigator decision. The primary endpoint is investigator‐based objective response rate per Response Evaluation Criteria in Solid Tumors, version 1.1. The secondary endpoints are progression‐free survival, overall survival, duration of response, and safety. Discussion This trial will provide evidence of the benefit and safety of pembrolizumab in combination with plinabulin and docetaxel in metastatic NSCLC patients who have been exposed and developed resistance to first‐line PD‐1/PD‐L1 inhibitor either as monotherapy or in combination with chemotherapy.https://doi.org/10.1111/1759-7714.14806immune checkpoint inhibitorsnon‐small cell lung cancerpembrolizumabplinabulinsecond‐line treatment |
| spellingShingle | Jia Liu Minjiang Chen Xiaoxing Gao Xiaoyan Liu Jing Zhao Ruili Pan Wei Zhong Yan Xu Mengzhao Wang Study protocol of KeyPemls‐004: A phase 2 study of pembrolizumab in combination with plinabulin and docetaxel in previously treated patients with metastatic non‐small cell lung cancer and progressive disease (PD) after immunotherapy (PD‐1/PD‐L1 inhibitor) alone or in combination with platinum‐doublet chemotherapy Thoracic Cancer immune checkpoint inhibitors non‐small cell lung cancer pembrolizumab plinabulin second‐line treatment |
| title | Study protocol of KeyPemls‐004: A phase 2 study of pembrolizumab in combination with plinabulin and docetaxel in previously treated patients with metastatic non‐small cell lung cancer and progressive disease (PD) after immunotherapy (PD‐1/PD‐L1 inhibitor) alone or in combination with platinum‐doublet chemotherapy |
| title_full | Study protocol of KeyPemls‐004: A phase 2 study of pembrolizumab in combination with plinabulin and docetaxel in previously treated patients with metastatic non‐small cell lung cancer and progressive disease (PD) after immunotherapy (PD‐1/PD‐L1 inhibitor) alone or in combination with platinum‐doublet chemotherapy |
| title_fullStr | Study protocol of KeyPemls‐004: A phase 2 study of pembrolizumab in combination with plinabulin and docetaxel in previously treated patients with metastatic non‐small cell lung cancer and progressive disease (PD) after immunotherapy (PD‐1/PD‐L1 inhibitor) alone or in combination with platinum‐doublet chemotherapy |
| title_full_unstemmed | Study protocol of KeyPemls‐004: A phase 2 study of pembrolizumab in combination with plinabulin and docetaxel in previously treated patients with metastatic non‐small cell lung cancer and progressive disease (PD) after immunotherapy (PD‐1/PD‐L1 inhibitor) alone or in combination with platinum‐doublet chemotherapy |
| title_short | Study protocol of KeyPemls‐004: A phase 2 study of pembrolizumab in combination with plinabulin and docetaxel in previously treated patients with metastatic non‐small cell lung cancer and progressive disease (PD) after immunotherapy (PD‐1/PD‐L1 inhibitor) alone or in combination with platinum‐doublet chemotherapy |
| title_sort | study protocol of keypemls 004 a phase 2 study of pembrolizumab in combination with plinabulin and docetaxel in previously treated patients with metastatic non small cell lung cancer and progressive disease pd after immunotherapy pd 1 pd l1 inhibitor alone or in combination with platinum doublet chemotherapy |
| topic | immune checkpoint inhibitors non‐small cell lung cancer pembrolizumab plinabulin second‐line treatment |
| url | https://doi.org/10.1111/1759-7714.14806 |
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