A Study of APG-1252 Plus Osimertinib(AZD9291) in EGFR TKI Resistant NSCLC Patients
brief summary
There are unmet medical needs in patients who resist to EGFR TKIs, especially to osimertinib; APG-1252 shows synergy with osimertinib in both osimertinib treatment naïve and resistant cell lines. This study is to explore the safety and efficacy of the combination of APG-1252 and osimertinib in 3rd generation TKI resistant patients and 3rd generation TKI treatment naïve patients.
detailed description
This is an open-label, single-arm, multicenter, phase 1b study and consists of two stages: dose finding and dose expansion.
The dose-finding stage will explore the safety and tolerability of APG-1252 at different dose levels combined with osimertinib mesylate tablets (hereinafter referred to as osimertinib) at a fixed dose level and determine the MTD and/or RP2D of APG-1252. According to the results from the ongoing phase 1 clinical trials (APG-1252-US-001, APG-1252-AU-001, APG-1252-CH-001) of APG-1252 currently, the starting dose of APG-1252 is set as 240 mg in the study. The 3+3 design will be implemented. The dose for successive cohorts will be escalated to 320 mg and 400 mg or de-escalated to 160 mg and 80 mg based on the safety of the starting dose.
During the dose-expansion period, the efficacy of APG-1252 combined with osimertinib will first be studied in patients with NSCLC that has progressed after treatment with third-generation EGFR TKIs. There will be a total of 20 subjects in Cohort 1. If at least one of the first 10 evaluable patients achieves a response (confirmed complete response \[CR\] or partial response \[PR\], assessed by the investigator as per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1) in the dose-expansion period, Cohort 2 and Cohort 3 will be initiated at the same time.
official title
A Phase Ib Study of Safety and Efficacy of APG-1252 in Combination With Osimertinib (AZD9291) in EGFR TKI Resistant NSCLC Patients