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SHR-A1811 (antibody-drug conjugate) in advanced HER2-mutant non-small cell lung cancer: a multicenter, open-label,
Ziming Li1, Zhengbo Song2, Wei Hong3
1Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200030, China.
Abstract:
A dose-escalation and expansion, phase 1/2 study (ClinicalTrials.gov, NCT04818333) was conducted to assess the novel antibody-drug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer (NSCLC). Here, we report results from the phase 1 portion. Patients who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2 to 8.0 mg/kg every 3 weeks. Dose escalation followed a Bayesian logistic regression model that included overdose control, with subsequent selection of tolerable levels for dose expansion. Overall, 63 patients were enrolled, including 43 receiving a recommended dose for expansion of 4.8 mg/kg. All patients had HER2-mutant disease. Dose-limiting toxicity occurred in one patient in the 8.0 mg/kg dose cohort. Grade ≥ 3 treatment-related adverse events occurred in 29 (46.0%) patients. One patient in the 6.4 mg/kg cohort died due to interstitial lung disease. As of April 11, 2023, the 4.8 mg/kg cohort showed an objective response rate of 41.9% (95% CI 27.0-57.9), and a disease control rate of 95.3% (95% CI 84.2-99.4). The median duration of response was 13.7 months, with 13 of 18 responses ongoing. The median progression-free survival was 8.4 months (95% CI 7.1-15.0). SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HER2-mutant NSCLC.
Insights
The novel antibody-drug conjugate SHR-A1811 shows promising efficacy and a favorable safety profile in patients with pretreated HER2-mutant advanced non-small cell lung cancer. This Phase 1 study highlights SHR-A1811 as a potential new treatment option for this challenging patient population.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Advanced non-small cell lung cancer (NSCLC) with HER2 alterations presents a therapeutic challenge, especially after failure of standard treatments.
- Novel therapeutic strategies are needed for patients with pretreated, HER2-altered advanced NSCLC.
Purpose of the Study:
- To assess the safety and efficacy of the novel antibody-drug conjugate SHR-A1811 in patients with pretreated HER2-altered advanced NSCLC.
- To determine the recommended dose for expansion in Phase 2 of the study.
Main Methods:
- A Phase 1/2 dose-escalation and expansion study (NCT04818333) enrolled patients with pretreated advanced NSCLC and HER2 alterations.
- Patients received SHR-A1811 intravenously, with dose escalation guided by a Bayesian logistic regression model.
- Safety and efficacy endpoints were evaluated, including objective response rate (ORR) and progression-free survival (PFS).
Main Results:
- The recommended dose for expansion was determined to be 4.8 mg/kg.
- In the 4.8 mg/kg cohort, the ORR was 41.9% and the disease control rate was 95.3%.
- Median duration of response was 13.7 months, and median PFS was 8.4 months, with manageable treatment-related adverse events.
Conclusions:
- SHR-A1811 demonstrated favorable safety and clinically meaningful efficacy in pretreated advanced HER2-mutant NSCLC.
- The study supports further investigation of SHR-A1811 in this patient population.
- SHR-A1811 represents a promising therapeutic option for HER2-altered NSCLC.
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