Intravenous liposomal irinotecan in metastatic triple-negative breast cancer after ≥ 2 prior lines of chemotherapy: a phase Ib study
Abstract This study (NCT04728035) aimed to explore the safety and efficacy of liposomal irinotecan (HE072) in patients with metastatic triple-negative breast cancer (mTNBC). This study consisted of two parts. In part 1, the 3 + 3 design was used to investigate three dose levels of HE072 (50, 70 and...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55090-4 |
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| author | Ying Fan Qingyuan Zhang Min Yan Xiujuan Qu Yongmei Yin Tao Sun Jin Yang Ying Wang Xu Wang Zhaofeng Niu Xinshuai Wang Sanyuan Sun Weihong Zhao Yanping Liu Miao Niu Xuemin Zhao Binghe Xu |
| author_facet | Ying Fan Qingyuan Zhang Min Yan Xiujuan Qu Yongmei Yin Tao Sun Jin Yang Ying Wang Xu Wang Zhaofeng Niu Xinshuai Wang Sanyuan Sun Weihong Zhao Yanping Liu Miao Niu Xuemin Zhao Binghe Xu |
| author_sort | Ying Fan |
| collection | DOAJ |
| description | Abstract This study (NCT04728035) aimed to explore the safety and efficacy of liposomal irinotecan (HE072) in patients with metastatic triple-negative breast cancer (mTNBC). This study consisted of two parts. In part 1, the 3 + 3 design was used to investigate three dose levels of HE072 (50, 70 and 90 mg/m2). In part 2, patients were enrolled in two cohorts (mTNBC and HER2-negative breast cancer brain metastasis [BCBM]), and received HE072 70 mg/m2 every two weeks (Q2W). The primary endpoints were maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), and treatment emergent adverse events (TEAEs). The secondary endpoints were pharmacokinetic profiles and efficacy including objective response rate (ORR) and disease control rate (DCR) (all patients) and Central Nervous System ORR and clinical benefit rate (CBR, for patients with HER2-negative BCBM), duration of response, progression free survival (PFS), overall survival (OS). A total of 119 patients were enrolled, including 101 mTNBC and 18 HER2-negative BCBM. One dose limiting toxicity (grade 3 nausea and vomiting) occurred at 70 mg/m2, and the MTD was not reached. The most common ≥ grade 3 TEAEs related to HE072 included neutropenia (21.0%), leukopenia (18.5%), diarrhea (10.1%). Among 87 evaluable patients with mTNBC, 22 patients (25.3%) achieved overall response. The DCR was 67.8% (59/87). The median PFS and OS were 4.8 months and 14.1 months, respectively. The RP2D was 70 mg/m2 Q2W. Promising antitumor activity in heavily pre-treated patients with mTNBC was observed, which warrants further validation. |
| format | Article |
| id | doaj-art-11d4b247c5f742a685a983edc2b369b6 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-11d4b247c5f742a685a983edc2b369b62025-01-05T12:40:17ZengNature PortfolioNature Communications2041-17232025-01-0116111010.1038/s41467-024-55090-4Intravenous liposomal irinotecan in metastatic triple-negative breast cancer after ≥ 2 prior lines of chemotherapy: a phase Ib studyYing Fan0Qingyuan Zhang1Min Yan2Xiujuan Qu3Yongmei Yin4Tao Sun5Jin Yang6Ying Wang7Xu Wang8Zhaofeng Niu9Xinshuai Wang10Sanyuan Sun11Weihong Zhao12Yanping Liu13Miao Niu14Xuemin Zhao15Binghe Xu16National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeHarbin Medical University Affiliated Cancer HospitalHenan Cancer HospitalThe First Affiliated Hospital of China Medical UniversityJiangsu Provincial People’s HospitalLiaoning Cancer HospitalThe First Affiliated Hospital of Xi’an Jiaotong UniversitySun Yat Sen Memorial Hospital of Sun Yat Sen UniversityTianjin Cancer HospitalYuncheng Central HospitalThe First Affiliated Hospital of Henan University of Science and TechnologyXuzhou Central HospitalChinese People’s Liberation Army General HospitalCSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., LtdCSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., LtdCSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., LtdNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract This study (NCT04728035) aimed to explore the safety and efficacy of liposomal irinotecan (HE072) in patients with metastatic triple-negative breast cancer (mTNBC). This study consisted of two parts. In part 1, the 3 + 3 design was used to investigate three dose levels of HE072 (50, 70 and 90 mg/m2). In part 2, patients were enrolled in two cohorts (mTNBC and HER2-negative breast cancer brain metastasis [BCBM]), and received HE072 70 mg/m2 every two weeks (Q2W). The primary endpoints were maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), and treatment emergent adverse events (TEAEs). The secondary endpoints were pharmacokinetic profiles and efficacy including objective response rate (ORR) and disease control rate (DCR) (all patients) and Central Nervous System ORR and clinical benefit rate (CBR, for patients with HER2-negative BCBM), duration of response, progression free survival (PFS), overall survival (OS). A total of 119 patients were enrolled, including 101 mTNBC and 18 HER2-negative BCBM. One dose limiting toxicity (grade 3 nausea and vomiting) occurred at 70 mg/m2, and the MTD was not reached. The most common ≥ grade 3 TEAEs related to HE072 included neutropenia (21.0%), leukopenia (18.5%), diarrhea (10.1%). Among 87 evaluable patients with mTNBC, 22 patients (25.3%) achieved overall response. The DCR was 67.8% (59/87). The median PFS and OS were 4.8 months and 14.1 months, respectively. The RP2D was 70 mg/m2 Q2W. Promising antitumor activity in heavily pre-treated patients with mTNBC was observed, which warrants further validation.https://doi.org/10.1038/s41467-024-55090-4 |
| spellingShingle | Ying Fan Qingyuan Zhang Min Yan Xiujuan Qu Yongmei Yin Tao Sun Jin Yang Ying Wang Xu Wang Zhaofeng Niu Xinshuai Wang Sanyuan Sun Weihong Zhao Yanping Liu Miao Niu Xuemin Zhao Binghe Xu Intravenous liposomal irinotecan in metastatic triple-negative breast cancer after ≥ 2 prior lines of chemotherapy: a phase Ib study Nature Communications |
| title | Intravenous liposomal irinotecan in metastatic triple-negative breast cancer after ≥ 2 prior lines of chemotherapy: a phase Ib study |
| title_full | Intravenous liposomal irinotecan in metastatic triple-negative breast cancer after ≥ 2 prior lines of chemotherapy: a phase Ib study |
| title_fullStr | Intravenous liposomal irinotecan in metastatic triple-negative breast cancer after ≥ 2 prior lines of chemotherapy: a phase Ib study |
| title_full_unstemmed | Intravenous liposomal irinotecan in metastatic triple-negative breast cancer after ≥ 2 prior lines of chemotherapy: a phase Ib study |
| title_short | Intravenous liposomal irinotecan in metastatic triple-negative breast cancer after ≥ 2 prior lines of chemotherapy: a phase Ib study |
| title_sort | intravenous liposomal irinotecan in metastatic triple negative breast cancer after ≥ 2 prior lines of chemotherapy a phase ib study |
| url | https://doi.org/10.1038/s41467-024-55090-4 |
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