This study will be a first-in-human study evaluating the safety and tolerability of FWD1509 MsOH in subjects with advanced NSCLC, when FWD1509 MsOH is administered once daily as a single agent. FWD1509 MsOH is an oral TKI (Tyrosine Kinase Inhibitor) that blocks the function of tyrosine kinase. TKIs such as gefitinib, erlotinib or afatinib are recommended as the first-line therapy for EGFR mutated (exon 19 deletions or L858R point mutations in exon 21) NSCLC patients. However, the majority (>50%) of patients will develop acquired resistance after initially responding to gefitinib or erlotinib due to the occurrence of secondary mutations (mostly T709M) in EGFR. Osimertinib was subsequently developed to such secondary mutations, but for EGFRex20ins mutations, on which there is still no effective therapies focusing. FWD1509 MsOH is new generation EGFR-TKI targeting EGFR mutations such as exon 19 deletion, L858R substitution as well as T790M mutations. In particular, FWD1509 MsOH targets the EGFRex20ins mutation in NSCLC. In addition to activity against EGFR mutations, FWD1509 MsOH is also active against a variety of HER2 mutations.~The development of FWD1509 MsOH at this stage is mainly focused on treatment of NSCLC tumors with EGFRex20ins mutations, followed by further exploration against other targets.
The purpose of this study is to characterize the safety and tolerability of FWD1509 MsOH in advanced NSCLC patients and establish the maximum tolerable dose (MTD), recommended phase 2 dose (RP2D) in advanced NSCLC patients.