24/012 DEFIANT

PHARAOH-A will determine the efficacy and tolerability of the combination of savolitinib and osimertinib in patients with EGFR-mutated, MET-overexpressed and/or amplified advanced NSCLC following disease progression on first- or second-line osimertinib. The primary endpoint is  objective tumour response rate (RECIST 1.1), with ctDNA dynamics and clearance to be examined in correlative studies. Patients with untreated and asymptomatic brain metastases can be included in the study. The study will also open to recruitment in Taiwan with first patient in expected in 2027.

The primary aim of this clinical trial is to evaluate whether radiotherapy delivered prior to standard treatment improves overall survival in patients with metastatic non-small cell lung cancer (NSCLC). The hypothesis is that early, highly targeted radiotherapy may reduce the risk of further metastatic spread, thereby improving survival outcomes. Similar interventions have shown event-free survival benefits in lung, prostate, and nasopharyngeal cancer trials. The trial builds on PRIME-Lung-pilot with 40 patients, which demonstrated that the intervention is safe and well-tolerated. Based on these findings, the trial will now expand to include more sites and a larger patient cohort.