724TiP - Phase II study of aumolertinib combined with metronomic oral vinorelbine and a platinum-based agent in patients with previously untreated EGFR-mutated advanced non-small cell lung cancer

Background

The OPAL and FLAURA2 studies showed osimertinib plus platinum-pemetrexed significantly improved progression-free survival (PFS) compared with osimertinib monotherapy in patients(pts) with EGFR-mutated advanced NSCLC at first-line treatment. However, the longer PFS benefit comes at the cost with higher toxicity, serious adverse events (AEs) from 5％ to 19％. In addition, pts need to receive intravenous Q3W for 2 years, which greatly reduces the convenience and compliance of treatment, also quality of life. The results of the NCT04646824 trial showed that Aumolertinib (a 3^rd EGFR-TKI) plus platinum-based chemotherapy provided a promising therapeutic strategy for advanced EGFR mutation NSCLC pts, even for the patients with CNS metastasis (ORR 89.4%) or harboring TP53 mutation (ORR 92.3%), this trial demonstrated a manageable safety profile, especially the grade 3 or 4 thrombocytopenia (2.9%). It's commonly known that oral vinorelbine plus cisplatin has been studied in numerous trials as first-line treatment of patients with NSCLC regardless of histological subtype. Metronomic chemotherapy, as a continuous administration of a cytotoxic agent, showed anti-tumor effect, an anti-angiogenic activity, a stimulation of the immune system, and a better tolerance. Therefore, we will proceed a prospective, multi-center, two-arm study to assess the efficacy and safety of aumolertinib combined with metronomic oral vinorelbine and a platinum-based agent versus aumolertinib monotherapy for EGFR-mutated stage ⅢB-Ⅳ NSCLC.

Trial design

Approximately 80 pts will voluntarily receive combination therapy (group A) or aumolertinib monotherapy (group B). Pts in group A will receive aumolertinib (110 mg once daily) plus oral vinorelbine 40mg three times weekly (Monday-Wednesday-Friday) and carboplatin AUC=5 or cisplatinum 75mg/m²(Q3W, 4 cycles). Those in group B will receive oral aumolertinib (110 mg once daily). The primary endpoint is PFS. The innovation of this project is that we hope to explore a combination treatment with more efficacy, less toxicity and convenient for advanced NSCLC with EGFR mutation.

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.