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SYS6010, epidermal growth factor receptor-targeting antibody-drug conjugate for advanced non-small cell lung cancer:
Zi-Ming Li1, Zhen Zhou1, Zhi-Yong He2
1Department of Medical Oncology, Shanghai Chest Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai Key Laboratory of Thoracic Tumor Biotherapy, Shanghai 200030, P.R. China.
Abstract:
SYS6010 is an antibody-drug conjugate targeting epidermal growth factor receptor (EGFR). We report the results of a phase 1 trial (ChiCTR2300072141) of SYS6010 in patients with non-small cell lung cancer (NSCLC). A total of 236 patients were treated. One dose-limiting toxicity occurred at 6.4 mg/kg; therefore, 4.2, 4.5, and 4.8 mg/kg were selected for cohort expansion. Treatment-related adverse events (TRAEs; any/grade ≥ 3) occurred in 99.6%/57.2% of patients. Common grade ≥3 TRAEs included neutropenia (30.9%), leukopenia (25.0%), and thrombocytopenia (17.4%). Objective response rate was 34.7% in EGFR-mutant NSCLC treated with EGFR tyrosine kinase inhibitors (TKIs) and platinum chemotherapy, 45.7% in EGFR-mutant NSCLC treated with EGFR TKIs, 20.0% in EGFR wild-type squamous NSCLC, and 35.7% in EGFR wild-type non-squamous NSCLC. Median progression-free survival and overall survival were 7.6 and 19.4 months, respectively, in EGFR-mutant NSCLC treated with EGFR TKIs and platinum chemotherapy. Overall, SYS6010 shows a manageable safety profile and encouraging antitumor activity in previously treated, advanced NSCLC.
Insights
SYS6010, an antibody-drug conjugate, demonstrated encouraging antitumor activity in advanced non-small cell lung cancer (NSCLC). The phase 1 trial revealed a manageable safety profile, with objective response rates varying by EGFR mutation status and prior treatment.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality worldwide.
- Epidermal growth factor receptor (EGFR) is a key target in NSCLC treatment.
- Novel therapeutic strategies, including antibody-drug conjugates, are needed for advanced NSCLC.
Purpose of the Study:
- To evaluate the safety and efficacy of SYS6010, an EGFR-targeting antibody-drug conjugate, in patients with advanced NSCLC.
- To determine the recommended dose for further clinical development.
- To assess the objective response rate (ORR) and survival outcomes in different NSCLC patient subgroups.
Main Methods:
- A Phase 1 clinical trial (ChiCTR2300072141) enrolled 236 patients with advanced NSCLC.
- Patients received SYS6010, with dose escalation and cohort expansion phases.
- Safety, including treatment-related adverse events (TRAEs), and efficacy (ORR, progression-free survival, overall survival) were assessed.
Main Results:
- One dose-limiting toxicity was observed at 6.4 mg/kg, leading to selection of 4.2, 4.5, and 4.8 mg/kg for expansion.
- TRAEs occurred in 99.6% of patients, with 57.2% experiencing Grade ≥3 events. Common Grade ≥3 TRAEs included neutropenia, leukopenia, and thrombocytopenia.
- ORRs ranged from 20.0% to 45.7% across different NSCLC subtypes and treatment histories. Median PFS and OS were 7.6 and 19.4 months, respectively, in a specific subgroup.
Conclusions:
- SYS6010 exhibits a manageable safety profile in previously treated, advanced NSCLC patients.
- The antibody-drug conjugate demonstrates encouraging antitumor activity across various NSCLC patient populations.
- SYS6010 warrants further investigation as a potential treatment option for advanced NSCLC.
