Osimertinib is standard of care for advanced EGFR-mutated NSCLC following emergence of T790M resistance mutation, with a median progression free survival of 10 months. Mechanisms of resistance to osimertinib are heterogeneous, and include acquisition of C979S mutations and loss of T790M mutations, which may result in resensitisation to 1st/2nd generation EGFR TKIs. Novel strategies are required to delay the emergence of resistance to osimertinib.
This open label, single-arm, multi-centre, phase II trial with safety run-in, will recruit 45 patients with EGFR-mutated NSCLC with demonstrated T790M resistance mutation acquired at progression on 1st/2nd generation EGFR TKI. Induction osimertinib 80mg daily will be given for 8 weeks (cycle 1 and 2), followed by alternating 28-day cycles of gefitinib 250mg PO daily and osimertinib 80mg daily until disease progression. Major endpoints include 12 month progression free survival (PFS12) (primary), time-to-progression, PFS, objective tumour response rate, overall survival, safety, changes in plasma EGFR mutation profile, T790M cfDNA over time and mechanisms of resistance. CT will be performed every 8 weeks on treatment, with translational research blood tests on day 1 of each 28-day cycle, and day 15 of cycles 3 and 4.
As of 8th August 2018, 13 of 16 planned sites are open and 22 patients have been recruited.
Oscillate is an investigator-initiated, co-operative group trial led by Australasian Lung Cancer Trials Group in collaboration with NHMRC Clinical Trials Centre, University of Sydney, with support from AstraZeneca. Australian New Zealand Clinical Trials Registry: ACTRN12617000720314.