PMID- 36575195 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230103 IS - 2374-4677 (Print) IS - 2374-4677 (Electronic) IS - 2374-4677 (Linking) VI - 8 IP - 1 DP - 2022 Dec 27 TI - Phase I study of LZM005 in patients with HER2-positive metastatic breast cancer. PG - 132 LID - 10.1038/s41523-022-00501-2 [doi] LID - 132 AB - 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. CI - (c) 2022. The Author(s). FAU - Xue, Cong AU - Xue C AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, P. R. China. AD - Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China. FAU - Li, Haifeng AU - Li H AUID- ORCID: 0000-0002-8883-9470 AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, P. R. China. AD - Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China. FAU - Yao, Herui AU - Yao H AD - Guangdong 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 University, Guangzhou, 510060, P. R. China. FAU - Lin, Ying AU - Lin Y AUID- ORCID: 0000-0002-5923-3306 AD - Breast Disease Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510060, P. R. China. FAU - An, Xin AU - An X AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, P. R. China. AD - Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China. FAU - Chen, Meiting AU - Chen M AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, P. R. China. AD - Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China. FAU - Huang, Riqing AU - Huang R AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, P. R. China. AD - Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China. FAU - Li, Lu AU - Li L AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, P. R. China. AD - Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China. FAU - Hu, Anqi AU - Hu A AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, P. R. China. AD - Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China. FAU - Ni, Mengqian AU - Ni M AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, P. R. China. AD - Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China. FAU - Zhang, Lulu AU - Zhang L AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, P. R. China. AD - Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China. FAU - Yang, Wei AU - Yang W AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, P. R. China. AD - Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China. FAU - Xu, Zhonghui AU - Xu Z AD - Livzon Pharmaceutical Group Inc, No.38, Chuangye North Road, Jinwan District, Zhuhai, Guangdong, P. R. China. FAU - Li, Su AU - Li S AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, P. R. China. lisu@sysucc.org.cn. AD - Department of Clinical Trial Center, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China. lisu@sysucc.org.cn. FAU - Shi, Yanxia AU - Shi Y AUID- ORCID: 0000-0002-5414-8049 AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, P. R. China. shiyx@sysucc.org.cn. AD - Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China. shiyx@sysucc.org.cn. LA - eng GR - 81773279/National Natural Science Foundation of China (National Science Foundation of China)/ GR - 82073391/National Natural Science Foundation of China (National Science Foundation of China)/ PT - Journal Article DEP - 20221227 PL - United States TA - NPJ Breast Cancer JT - NPJ breast cancer JID - 101674891 PMC - PMC9794829 COIS- Zh.X. declares no competing non-financial Interests but the following competing financial Interests. He is an employee of Livzon. All other authors declare no competing interests. EDAT- 2022/12/28 06:00 MHDA- 2022/12/28 06:01 PMCR- 2022/12/27 CRDT- 2022/12/27 23:21 PHST- 2022/04/05 00:00 [received] PHST- 2022/12/13 00:00 [accepted] PHST- 2022/12/27 23:21 [entrez] PHST- 2022/12/28 06:00 [pubmed] PHST- 2022/12/28 06:01 [medline] PHST- 2022/12/27 00:00 [pmc-release] AID - 10.1038/s41523-022-00501-2 [pii] AID - 501 [pii] AID - 10.1038/s41523-022-00501-2 [doi] PST - epublish SO - NPJ Breast Cancer. 2022 Dec 27;8(1):132. doi: 10.1038/s41523-022-00501-2.