Abstract 1201TiP
Background
The majority of uncommon epidermal growth factor receptor mutations (EGFRm) showed decreased sensitivity to EGFR- tyrosine kinase inhibitor (TKI) when compared to common EGFRm. Osimertinib as first-line therapy showed promising efficacy in non-small cell lung cancer (NSCLC) patients with EGFR G719X/L861Q/S768I mutations. While the addition of chemotherapy to gefitinib markedly improved the progression-free survival and overall survival of sensitive EGFRm NSCLC, with an acceptable toxicity profile, osimertinib in combination with chemotherapy may extend the clinical benefits in uncommon EGFRm NSCLC. This study will evaluate the efficacy and safety of osimertinib plus platinum and pemetrexed chemotherapy in untreated locally advanced/metastatic NSCLC patients with uncommon EGFRm.
Trial design
This is a phase II, open-label, single arm, multicenter and exploratory study. Stage IIIB-IVB treatment-naïve non-squamous NSCLC patients with at least 1 of the 4 uncommon EGFRm (G719X/L861Q/S768I/de novo T790M) but without ex19del/L858R will be enrolled. Those with asymptomatic and stable central nervous system (CNS) metastases are eligible. The subjects (N = 35) will receive 80mg osimertinib QD p.o. plus standard chemotherapy composed of cisplatin or carboplatin and pemetrexed i.v. on Day 1 of a 21-day cycle (every 3 weeks) for 4 to 6 cycles, followed by osimertinib 80 mg QD p.o. plus pemetrexed maintenance i.v. every 3 weeks until RECIST 1.1-defined radiological progression or intolerance as judged by the investigator. The primary outcome endpoint is objective response rate (ORR, per RECIST 1.1 using investigator assessments). Secondary endpoints include progression-free survival (PFS) and overall survival (OS), duration of response (DoR), disease control rate (DCR), depth of response, time to treatment failure or death (TTF) and time to first subsequent therapy or death (TFST) (all assessed by investigator per RECIST 1.1). Resistance profile in plasma circulating tumor deoxyribonucleic acid (ctDNA) will be evaluated as exploratory endpoint.
Clinical trial identification
NCT05215951.
Editorial acknowledgement
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
All authors have declared no conflicts of interest.