Phase I study of LZM005 in patients with HER2-positive metastatic breast cancer
Abstract The prognosis of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer (MBC) remained unsatisfactory currently, more anti-HER2 agents are needed. Here we report a phase I study that evaluated the safety, activity, and biomarkers of LZM005, a HER2 antibody, used a...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-12-01
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| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-022-00501-2 |
| _version_ | 1797642149440782336 |
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| author | Cong Xue Haifeng Li Herui Yao Ying Lin Xin An Meiting Chen Riqing Huang Lu Li Anqi Hu Mengqian Ni Lulu Zhang Wei Yang Zhonghui Xu Su Li Yanxia Shi |
| author_facet | Cong Xue Haifeng Li Herui Yao Ying Lin Xin An Meiting Chen Riqing Huang Lu Li Anqi Hu Mengqian Ni Lulu Zhang Wei Yang Zhonghui Xu Su Li Yanxia Shi |
| author_sort | Cong Xue |
| collection | DOAJ |
| description | Abstract The prognosis of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer (MBC) remained unsatisfactory currently, more anti-HER2 agents are needed. Here we report a phase I study that evaluated the safety, activity, and biomarkers of LZM005, a HER2 antibody, used as a monotherapy or in combination with trastuzumab plus docetaxel in patients with HER2-positive MBC. From October 2017 to December 2019, 34 patients received LZM005 (14 monotherapy, 20 combination therapy). No DLT was observed. The common adverse events (AEs) in phase Ia included diarrhea (21.4%), infusion reaction (21.4%), and hypertriglyceridemia (21.4%), while those in phase Ib were leukopenia (85.0%), neutropenia (75.0%), anemia (60.0%), diarrhea (60.0%), and rash/pruritus (50.0%). All AEs were manageable. In phase Ia, partial response (PR) was achieved in one case (1/14, overall response rate [ORR]: 7.1%); the disease control rate was 42.90% (6/14). In phase Ib, 11 patients (55.0%) achieved PR, and eight (40.0%) had stable disease. The ORR was 100% (6/6) in trastuzumab-naive and 35.7% (5/14) in trastuzumab-pretreated patients. Biomarker analysis showed that chromatin remodeling genes KMT2B and BRWD1 were associated with better progression-free survival. LZM005 is well tolerated and shows potent activity in patients with HER2-positive MBC. |
| first_indexed | 2024-03-11T13:56:02Z |
| format | Article |
| id | doaj.art-3c78c32b658b45459753325792a0432e |
| institution | Directory Open Access Journal |
| issn | 2374-4677 |
| language | English |
| last_indexed | 2024-03-11T13:56:02Z |
| publishDate | 2022-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj.art-3c78c32b658b45459753325792a0432e2023-11-02T06:46:33ZengNature Portfolionpj Breast Cancer2374-46772022-12-01811810.1038/s41523-022-00501-2Phase I study of LZM005 in patients with HER2-positive metastatic breast cancerCong Xue0Haifeng Li1Herui Yao2Ying Lin3Xin An4Meiting Chen5Riqing Huang6Lu Li7Anqi Hu8Mengqian Ni9Lulu Zhang10Wei Yang11Zhonghui Xu12Su Li13Yanxia Shi14State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer CenterGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Medical Oncology, Phase I Clinical Trial Centre, Sun Yat-sen Memorial Hospital of Sun Yat-sen UniversityBreast Disease Center, The First Affiliated Hospital, Sun Yat‐Sen UniversityState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer CenterLivzon Pharmaceutical Group IncState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer CenterAbstract The prognosis of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer (MBC) remained unsatisfactory currently, more anti-HER2 agents are needed. Here we report a phase I study that evaluated the safety, activity, and biomarkers of LZM005, a HER2 antibody, used as a monotherapy or in combination with trastuzumab plus docetaxel in patients with HER2-positive MBC. From October 2017 to December 2019, 34 patients received LZM005 (14 monotherapy, 20 combination therapy). No DLT was observed. The common adverse events (AEs) in phase Ia included diarrhea (21.4%), infusion reaction (21.4%), and hypertriglyceridemia (21.4%), while those in phase Ib were leukopenia (85.0%), neutropenia (75.0%), anemia (60.0%), diarrhea (60.0%), and rash/pruritus (50.0%). All AEs were manageable. In phase Ia, partial response (PR) was achieved in one case (1/14, overall response rate [ORR]: 7.1%); the disease control rate was 42.90% (6/14). In phase Ib, 11 patients (55.0%) achieved PR, and eight (40.0%) had stable disease. The ORR was 100% (6/6) in trastuzumab-naive and 35.7% (5/14) in trastuzumab-pretreated patients. Biomarker analysis showed that chromatin remodeling genes KMT2B and BRWD1 were associated with better progression-free survival. LZM005 is well tolerated and shows potent activity in patients with HER2-positive MBC.https://doi.org/10.1038/s41523-022-00501-2 |
| spellingShingle | Cong Xue Haifeng Li Herui Yao Ying Lin Xin An Meiting Chen Riqing Huang Lu Li Anqi Hu Mengqian Ni Lulu Zhang Wei Yang Zhonghui Xu Su Li Yanxia Shi Phase I study of LZM005 in patients with HER2-positive metastatic breast cancer npj Breast Cancer |
| title | Phase I study of LZM005 in patients with HER2-positive metastatic breast cancer |
| title_full | Phase I study of LZM005 in patients with HER2-positive metastatic breast cancer |
| title_fullStr | Phase I study of LZM005 in patients with HER2-positive metastatic breast cancer |
| title_full_unstemmed | Phase I study of LZM005 in patients with HER2-positive metastatic breast cancer |
| title_short | Phase I study of LZM005 in patients with HER2-positive metastatic breast cancer |
| title_sort | phase i study of lzm005 in patients with her2 positive metastatic breast cancer |
| url | https://doi.org/10.1038/s41523-022-00501-2 |
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