Abstract 1370TiP
Background
EGFR-TKI provide superior efficacy to chemotherapy in the treatment of EGFE-mutant advanced NSCLC. However, most patients will develop variable degrees of resistance after receiving first/second-generation EGFR-TKI treatment, highlighting the urgent need for novel agents. Befotertinib (D-0316) is a third-generation EGFR-TKI that is selective to EGFR-sensitizing mutations (exon 21 L858R mutation and exon 19 deletion) or T790M mutation. Its efficacy has been confirmed in a phase II study (NCT03861156), which reported an objective response rate (ORR) of 64.8% and a disease control rate (DCR) of 95.2% in NSCLC patients with EGFR T790M who progressed on previous treatment with first-line EGFR-TKIs. Based on the above findings, we conducted a multicenter, randomized, open-label, controlled phase III study to evaluate the efficacy, safety, and tolerability of befotertinib versus icotonib as first-line treatment for advanced or metastatic EGFR-mutations NSCLC.
Trial design
Treatment-naive patients with locally advanced or metastatic NSCLC harboring positive EGFR mutation were eligible. The sample size was specified assuming a hazard ratio (HR) of 0.625, corresponding with an increase in progression free survival (PFS) from an expected 10 months for icotinib to 16 months for befotertinib. To provide an 86% power at a two-sided 5% significance level, and an estimated 20% dropout rate, a total of 360 patients are required. Eligible patients will be randomized 1:1 ratio assigned to receive icotinib (125 mg tid orally) or befotertinib (100 mg once daily with a 21-day lead-in at 75 mg once daily), until disease progression or death. The primary endpoint was PFS assessed by an independent review committee. Secondary endpoints included ORR, DCR, intracranial objective response rate (iORR), intracranial progression-free survival (iPFS), overall survival (OS), duration of response (DOR) and safety. Progression: The study was conducted in 40 centers in China. As of 18 December, 2020, the recruitment was completed.
Clinical trial identification
NCT04206072.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Betta Pharmaceuticals Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.