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A Novel Third-generation EGFR Tyrosine Kinase Inhibitor Abivertinib for EGFR T790M-mutant Non-Small Cell Lung Cancer:
1Department of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
Purpose:
To establish recommended phase II dose (RP2D) in phase I and evaluate safety and efficacy of abivertinib in patients with EGFR Thr790Met point mutation (T790M)-positive(+) non-small cell lung cancer (NSCLC) with disease progression from prior EGFR inhibitors in phase II.
Patients And Methods:
This multicenter, open-label study included 367 adult Chinese patients. Abivertinib at doses of 50 mg twice a day to 350 mg twice a day was evaluated in phase I in continual 28-day cycles, and the RP2D of 300 mg twice a day was used in phase II in continual 21-day cycles. Primary endpoints include RP2D in phase I and objective response rate (ORR) at RP2D in phase II.
Results:
The RP2D of 300 mg twice a day for abivertinib was established based on pharmacokinetics, efficacy, and safety profiles across doses in phase I. In phase II, 227 patients received RP2D for a median treatment duration of 24.6 weeks (0.43-129). Among 209 response-evaluable patients, confirmed ORR was 52.2% [109/209; 95% confidence interval (CI): 45.2-59.1]. Disease control rate (DCR) was 88.0% (184/209; 95% CI: 82.9-92.1). The median duration of response (DoR) and progression-free survival (PFS) was 8.5 months (95% CI: 6.1-9.2) and 7.5 months (95% CI: 6.0-8.8), respectively. The median overall survival (OS) was 24.9 months [95% CI: 22.4-not reachable (NR)]. All (227/227) patients reported at least 1 adverse event (AE), with 96.9% (220/227) of treatment-related AEs. Treatment-related serious AEs were reported in 13.7% (31/227) of patients. Death was reported in 4.4% (10/227) of patients, and none was deemed as treatment-related.
Conclusions:
Abivertinib of 300 mg twice a day demonstrated favorable clinical efficacy with manageable side effects in patients with EGFR T790M+ NSCLC.
Insights
Abivertinib at 300 mg twice daily shows efficacy in non-small cell lung cancer (NSCLC) with EGFR T790M mutations. The drug demonstrated a 52.2% objective response rate and manageable side effects.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide.
- Epidermal Growth Factor Receptor (EGFR) mutations, particularly the T790M resistance mutation, are key drivers in a subset of NSCLC patients.
- Acquired resistance to first-generation EGFR inhibitors necessitates the development of novel therapeutic strategies.
Purpose of the Study:
- To determine the recommended Phase II dose (RP2D) of abivertinib in a Phase I study.
- To evaluate the safety and efficacy of abivertinib in patients with EGFR T790M-positive (+) NSCLC who have progressed on prior EGFR inhibitors in a Phase II study.
Main Methods:
- A multicenter, open-label study involving 367 adult Chinese patients.
- Phase I: Abivertinib doses from 50 mg BID to 350 mg BID evaluated over 28-day cycles.
- Phase II: Utilized the RP2D of 300 mg BID over 21-day cycles, with objective response rate (ORR) as a primary endpoint.
Main Results:
- The RP2D of abivertinib was established at 300 mg twice daily based on pharmacokinetic, efficacy, and safety data.
- In Phase II, 227 patients received the RP2D. The confirmed ORR was 52.2% (109/209), with a disease control rate (DCR) of 88.0% (184/209).
- Median progression-free survival (PFS) was 7.5 months, and median overall survival (OS) was 24.9 months. Treatment-related adverse events were reported in 96.9% of patients, with serious AEs in 13.7%.
Conclusions:
- Abivertinib at 300 mg twice daily is an effective treatment for patients with EGFR T790M+ NSCLC who have progressed on prior EGFR inhibitors.
- The drug demonstrated a favorable efficacy profile, including significant ORR and survival benefits.
- Abivertinib was associated with manageable side effects, supporting its potential role in NSCLC treatment.
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