420TiP - UpSwinG: Real-world study of TKI activity in patients with EGFR mutation-positive (EGFRm+) NSCLC with uncommon mutations, and sequencing of afatinib followed by osimertinib

Background

EGFR TKIs are established as an effective treatment for patients with EGFRm+ NSCLC harboring common mutations (Del19 or L858R). However, 7% to 23% of NSCLC tumors harbor uncommon EGFR mutations, where EGFR TKI efficacy is less established. Up to 75% of patients treated with afatinib develop T790M resistance. Second-line osimertinib is highly effective in these patients. In the GioTag study, sequential afatinib and osimertinib was associated with encouraging outcomes (median TTF and OS: 28.1 and 41.3 months, respectively) in 203 patients who developed T790M mutations after first-line therapy in a real-world setting.

Trial design

This real-world, non-interventional, global, multi-center study (UpSwinG; NCT04179890) will enroll ∼400 patients with EGFR TKI-naïve advanced (stage IIIB/IV) EGFRm+ NSCLC treated with EGFR TKIs across ∼65 study centers in ≤11 countries. Pre-existing data will be retrospectively collected from medical records (paper or electronic); selection bias will be minimized where possible, including by selecting only consecutive patients meeting each of the inclusion criteria and none of the exclusion criteria. The study comprises two cohorts (∼200 patients each). Cohort 1 will include patients with tumors harboring uncommon or compound EGFR mutations who received first- or second-line EGFR TKI treatment. Cohort 2 will include patients with common EGFR mutations who progressed on first-line afatinib, tested positive for T790M and were subsequently treated with second-line osimertinib (40 or 80 mg/day). Key exclusion criteria include prior participation in other EGFRm+ NSCLC studies and patients with active brain metastases. Across both cohorts, the primary objective will be time on treatment, defined from the start of EGFR TKI treatment until the end of EGFR TKI treatment or death by any cause in cohort 1, and from the start of first-line until the end of second-line treatment or death by any cause in cohort 2. Secondary objectives include overall response rate, overall survival, and time on second-line treatment (in cohort 1). Thus far, 256 patients have been recruited: 206 in cohort 1, and 50 in cohort 2.

Clinical trial identification

NCT04179890.

Legal entity responsible for the study

Boehringer Ingelheim.

Funding

Boehringer Ingelheim.

Disclosure

S. Miura: Advisory/Consultancy, Speaker Bureau/Expert testimony: Chugai Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Speaker Bureau/Expert testimony: Taiho Pharma; Speaker Bureau/Expert testimony: Ono Pharma; Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Abbvie; Speaker Bureau/Expert testimony: Kyowa Hakko Kirin. A. Märten: Full/Part-time employment: Boehringer Ingelheim. S. Popat: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Takeda; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AZ; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy: EMD Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Guardant Health; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy: Paradox; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Ariad.