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 (Anti-PD-1/PD-L1 inhibitor) alone or in combination with platinum-doublet chemotherapy
Background: Immune checkpoint inhibitor (ICI)-based treatment regimens have become the standard of care for first-line treatment of NSCLC. Once progressed, it is not recommended to continue using ICI monotherapy, and the efficacy of chemotherapy is limited (ORR ∼10% with doc), so there is a high unm...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | The Lancet Regional Health. Western Pacific |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666606524003006 |
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| author | Yan Xu Xiaoxing Gao Minjiang Chen Xiaoyan Liu Jing Zhao Wei Zhong Mengzhao Wang |
| author_facet | Yan Xu Xiaoxing Gao Minjiang Chen Xiaoyan Liu Jing Zhao Wei Zhong Mengzhao Wang |
| author_sort | Yan Xu |
| collection | DOAJ |
| description | Background: Immune checkpoint inhibitor (ICI)-based treatment regimens have become the standard of care for first-line treatment of NSCLC. Once progressed, it is not recommended to continue using ICI monotherapy, and the efficacy of chemotherapy is limited (ORR ∼10% with doc), so there is a high unmet clinical need. Plin is a selective immunomodulating microtubule-binding agent which promotes dendritic cell maturation and enhances anti-tumor T cell response, and have the potential to overcome immunotherapy resistance as a novel regimen in combination with pemb and doc. This phase 2 study was aimed to evaluate the efficacy and safety of pemb plus plin and doc in pts with metastatic NSCLC who had progressed after ICI. Methods: In this investigator-initiated, single-arm, open-label, phase 2 trial, metastatic NSCLC pts who acquired resistance after ICI treatment were enrolled (Clinical trial information: NCT05599789). Participants received pemb 200 mg D1, plin 30 mg/m2 D1 and doc 75 mg/m2 D1 intravenously for a 21-day cycle. The primary endpoint was investigator-based ORR per RECIST 1.1. The secondary endpoints included PFS, OS, DoR and toxicity. Kaplan-Meier method is used for OS, PFS, and DOR analysis. The study intends to enroll 47 patients with a formal interim analysis at 19 patients enrolled. Findings: 38 pts were enrolled and 35 pts evaluable ITT population were analyzed at data cutoff on 10/10/2024. Median follow-up was 8.8 months (M) and median age was 68.0 (50-83) with 77.1% male and 22.9% female. 65.7% were current or former smokers. Histology included 60% with non-squamous, 40% with squamous cell carcinoma. Confirmed ORR was 18.2%. DCR was 89.7% (defined as PR and SD > 4 M), median DoR was 11.4 M, median PFS was 8.3 M (current 6 M PFS rate was 70.4%, 12 M PFS rate was 42.7%), and OS had not been reached. 48.6% of pts experienced G3 or higher treatment-related AEs. Interpretation: With good tolerability, pemb plus plin and doc in pts with metastatic NSCLC who progressed after clinical benefit to ICI demonstrated promising efficacy. |
| format | Article |
| id | doaj-art-aa0cb68f37a74c37b461e548f15c0edc |
| institution | DOAJ |
| issn | 2666-6065 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | The Lancet Regional Health. Western Pacific |
| spelling | doaj-art-aa0cb68f37a74c37b461e548f15c0edc2025-08-20T02:43:29ZengElsevierThe Lancet Regional Health. Western Pacific2666-60652025-02-015510130610.1016/j.lanwpc.2024.101306A 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 (Anti-PD-1/PD-L1 inhibitor) alone or in combination with platinum-doublet chemotherapyYan Xu0Xiaoxing Gao1Minjiang Chen2Xiaoyan Liu3Jing Zhao4Wei Zhong5Mengzhao Wang6Peking Union Medical College Hospital, ChinaPeking Union Medical College Hospital, ChinaPeking Union Medical College Hospital, ChinaPeking Union Medical College Hospital, ChinaPeking Union Medical College Hospital, ChinaPeking Union Medical College Hospital, ChinaPeking Union Medical College Hospital, ChinaBackground: Immune checkpoint inhibitor (ICI)-based treatment regimens have become the standard of care for first-line treatment of NSCLC. Once progressed, it is not recommended to continue using ICI monotherapy, and the efficacy of chemotherapy is limited (ORR ∼10% with doc), so there is a high unmet clinical need. Plin is a selective immunomodulating microtubule-binding agent which promotes dendritic cell maturation and enhances anti-tumor T cell response, and have the potential to overcome immunotherapy resistance as a novel regimen in combination with pemb and doc. This phase 2 study was aimed to evaluate the efficacy and safety of pemb plus plin and doc in pts with metastatic NSCLC who had progressed after ICI. Methods: In this investigator-initiated, single-arm, open-label, phase 2 trial, metastatic NSCLC pts who acquired resistance after ICI treatment were enrolled (Clinical trial information: NCT05599789). Participants received pemb 200 mg D1, plin 30 mg/m2 D1 and doc 75 mg/m2 D1 intravenously for a 21-day cycle. The primary endpoint was investigator-based ORR per RECIST 1.1. The secondary endpoints included PFS, OS, DoR and toxicity. Kaplan-Meier method is used for OS, PFS, and DOR analysis. The study intends to enroll 47 patients with a formal interim analysis at 19 patients enrolled. Findings: 38 pts were enrolled and 35 pts evaluable ITT population were analyzed at data cutoff on 10/10/2024. Median follow-up was 8.8 months (M) and median age was 68.0 (50-83) with 77.1% male and 22.9% female. 65.7% were current or former smokers. Histology included 60% with non-squamous, 40% with squamous cell carcinoma. Confirmed ORR was 18.2%. DCR was 89.7% (defined as PR and SD > 4 M), median DoR was 11.4 M, median PFS was 8.3 M (current 6 M PFS rate was 70.4%, 12 M PFS rate was 42.7%), and OS had not been reached. 48.6% of pts experienced G3 or higher treatment-related AEs. Interpretation: With good tolerability, pemb plus plin and doc in pts with metastatic NSCLC who progressed after clinical benefit to ICI demonstrated promising efficacy.http://www.sciencedirect.com/science/article/pii/S2666606524003006 |
| spellingShingle | Yan Xu Xiaoxing Gao Minjiang Chen Xiaoyan Liu Jing Zhao Wei Zhong Mengzhao Wang 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 (Anti-PD-1/PD-L1 inhibitor) alone or in combination with platinum-doublet chemotherapy The Lancet Regional Health. Western Pacific |
| title | 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 (Anti-PD-1/PD-L1 inhibitor) alone or in combination with platinum-doublet chemotherapy |
| title_full | 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 (Anti-PD-1/PD-L1 inhibitor) alone or in combination with platinum-doublet chemotherapy |
| title_fullStr | 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 (Anti-PD-1/PD-L1 inhibitor) alone or in combination with platinum-doublet chemotherapy |
| title_full_unstemmed | 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 (Anti-PD-1/PD-L1 inhibitor) alone or in combination with platinum-doublet chemotherapy |
| title_short | 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 (Anti-PD-1/PD-L1 inhibitor) alone or in combination with platinum-doublet chemotherapy |
| title_sort | 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 anti pd 1 pd l1 inhibitor alone or in combination with platinum doublet chemotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S2666606524003006 |
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