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S. Dawson
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P2.03 - Chemotherapy/Targeted Therapy (ID 704)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-044 - OSCILLATE - Phase 2 Trial of Alternating Osimertinib with Gefitinib in Patients with EGFR-T790M Mutation Positive Advanced NSCLC (ID 9711)
09:30 - 09:30 | Author(s): S. Dawson
- Abstract
Background:
Activating mutations of the epidermal growth factor receptor (EGFR) are key drivers of non-small cell lung cancer (NSCLC) in approximately 10-15% of Western patients and 30-35% of Asian patients. Patients with common activating mutations (L858R and del19) typically have objective tumour response rates (OTRR) of 56-74% and median progression free survival (PFS) of 9-13 months with first-generation EGFR tyrosine kinase inhibitors (TKI) such as erlotinib or gefitinib. The most common mechanism of acquired resistance to first generation EGFR TKI is the T790M mutation (50-60% of cases). Osimertinib is an irreversible EGFR TKI effective against the T790M resistance mutation with OTRR of 51-71% in T790M positive disease. However, acquired resistance invariably develops, and median PFS is approximately 10 months. Mechanisms of resistance include C797S mutations and loss of T790M. Novel strategies that prevent or delay resistance to osimertinib are likely to enhance its durability of response and clinical benefit in EGFR-T790M positive NSCLC.
Method:
DESIGN: Open-label, single arm, multi-centre, phase 2 trial with safety run in. ELIGIBILITY: Adults with advanced, EGFR mutated NSCLC, acquired resistance to first or second generation EGFR TKIs, and mutation of T790M. ENDPOINTS: PFS rate at 12 months, feasibility of alternating osimertinib and gefitinib, time to progression and PFS time, objective tumour response rate, overall survival and adverse events. Tertiary correlative objectives include changes in plasma cfDNA levels for activating EGFR mutations and T790M over time, their relationships with OTRR and the mechanism of resistance. TREATMENT: Osimertinib 80mg daily for 8 weeks (2 cycles), then gefitinib 250mg daily for 4 weeks alternating with osimertinib 80mg daily for 4 weeks (i.e. alternating 4 weekly cycles of each drug) until disease progression or prohibitive toxicity. STATISTICS: A total of 45 participants provides 90% power, with a 1-sided type 1 error rate of 10%, to distinguish the observed proportion alive and progression free at 12 months from true rates of 45% (not worthy of pursuit) and 65% (worthy of pursuit) using a Simon, 2-stage, minimax design allowing for 4 ineligible or inevaluable participants. ASSESSMENT: CT scans 8-weekly until disease progression. Plasma collections at baseline and at the start of each 4-week cycle. OSCILLATE is an investigator-initiated cooperative-group trial led by ALTG, in collaboration with NHMRC Clinical Trials Centre, University of Sydney, with support from Astra-Zeneca.
Result:
Section not applicable
Conclusion:
Section not applicable
