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Phase I study of LZM005 in patients with HER2-positive metastatic breast cancer
Cong Xue1,2, Haifeng Li1,2, Herui Yao3
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, P. R. China.
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.
Insights
LZM005, a new HER2 antibody, shows promising activity and is well-tolerated in patients with HER2-positive metastatic breast cancer (MBC). This phase I study indicates LZM005 is a potential new treatment option for MBC.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) has a poor prognosis, necessitating novel anti-HER2 therapies.
- Current treatment options for HER2-positive MBC require further development to improve patient outcomes.
Purpose of the Study:
- To evaluate the safety, activity, and biomarkers of LZM005, a novel HER2 antibody, as monotherapy and in combination with trastuzumab plus docetaxel.
- To assess the efficacy of LZM005 in patients with HER2-positive MBC.
Main Methods:
- A Phase I clinical trial involving 34 patients with HER2-positive MBC.
- Patients received LZM005 as monotherapy (n=14) or in combination with trastuzumab and docetaxel (n=20).
- Safety, adverse events, overall response rate (ORR), and disease control rate were assessed. Biomarker analysis was performed.
Main Results:
- LZM005 was well-tolerated with manageable adverse events in both monotherapy and combination arms.
- Partial response (PR) was observed in 7.1% (monotherapy) and 55.0% (combination therapy) of patients.
- The ORR was 100% in trastuzumab-naive patients and 35.7% in trastuzumab-pretreated patients in the combination arm.
- Chromatin remodeling genes KMT2B and BRWD1 were linked to improved progression-free survival.
Conclusions:
- LZM005 demonstrates a favorable safety profile and potent anti-tumor activity in HER2-positive MBC.
- LZM005 represents a promising therapeutic candidate for HER2-positive MBC, particularly in trastuzumab-naive patients.
- Biomarker analysis suggests potential predictive markers for treatment response.
