599TiP - A prospective study of savolitinib plus docetaxel in pretreated EGFR/ALK/ROS1/METex14m-wildtype advanced NSCLC patients with MET overexpression (FirstMET)

Background

Hepatocyte growth factor receptor (HGF)/mesothelial-epithelial transition (MET) pathway activation is known as an oncogenic driver in NSCLC. MET overexpression has been reported to be associated with worse clinical outcomes of NSCLCs. In China, the current second-line standard of care for EGFR/ALK/ROS1/METex14m-wildtype NSCLC with MET overexpression is mono-chemotherapy or immune checkpoint inhibitor, but with limited efficacy. Preclinically, the synergistic effect of savolitinib and docetaxel was tested in both CDX and PDX models. A phase I study explored the safety and tolerability of savolitinb plus docetaxel in advanced solid tumors. This study (NCT05777278) aims to explore the efficacy and safety of savolitinib plus docetaxel in pretreated EGFR/ALK/ROS1/METex14m-wildtype advanced NSCLC patients with MET overexpression.

Trial design

This is an ongoing, phase I/II, pilot, open-label, single arm, single center, interventional study. Eligible patients will be those diagnosed with MET overexpression, EGFR/ALK/ROS1/METex14m-wildtype NSCLC in advanced stages and not treated with MET inhibitors. MET overexpression is defined as IHC 3+ in ≥50% of tumor cells. Patients will receive docetaxel (60 mg/m2, ivgtt, q3w) and savolitinib (300mg or 200mg according to safety run-in recommendation, p.o., BID) after signing informed consent. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, other discontinuation criterion is met, or study completion. The primary objectives include assessing the efficacy by Objective Response Rate (ORR) and the safety and tolerability profile of savolitinib plus docetaxel in pretreated EGFR/ALK/ROS1/METex14m-wildtype advanced NSCLC patients with MET overexpression. The secondary objective is to assess the efficacy through Progression-Free Survival (PFS), Duration of Response (DoR), Disease Control Rate (DCR), Overall Survival (OS), 12 months OS rate using investigator assessments according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). The exploratory objective is to assess efficacy in the MET-high (in 90% tumor cells IHC 3+) population.

Clinical trial identification

NCT05777278, 03/17/2023.

Legal entity responsible for the study

The authors.

Funding

AstraZeneca, China and Hutchison Whampoa, China.

Disclosure

All authors have declared no conflicts of interest.