Rationale and design of phase II clinical trial of dual inhibition with ramucirumab and erlotinib in EGFR exon 19 deletion-positive treatment-naive non-small cell lung cancer with high PD-L1 expression (SPIRAL-3D study)

Background:Osimertinib is a standard treatment option for epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). However, osimertinib monotherapy yields poor clinical outcomes in some patients, necessitating the development of novel treatment strategies. In addition, several studies have suggested that high programmed cell death-ligand 1 (PD-L1) expression is associated with poor progression-free survival (PFS) for osimertinib monotherapy in patients with advanced NSCLC harboring EGFR mutations. Objective:To evaluate the clinical efficacy of erlotinib plus ramucirumab for EGFR exon 19 deletion-positive treatment-naive NSCLC with high PD-L1 expression. Design:A single-arm, prospective, open-label, phase II study Methods and Analysis:Patients with treatment-naive EGFR exon 19 deletion-positive NSCLC with high PD-L1 expression and a performance status of 0-2 will receive combination therapy with erlotinib plus ramucirumab until evidence of disease progression or development of unacceptable toxicity. High PD-L1 expression is defined as a tumor proportion score of 50% or higher, as determined by PD-L1 immunohistochemistry 22C3 pharmDx testing. The Kaplan-Meier method and the Brookmeyer and Crowley method with the arcsine square-root transformation will be used with PFS as the primary endpoint. The secondary endpoints include overall response rate, disease control rate, overall survival, and safety. A total of 25 patients will be enrolled. Ethics:The study has been approved by the Clinical Research Review Board, Kyoto Prefectural University of Medicine, Kyoto, Japan, and written informed consent will be obtained from all patients. Discussion:To the best of our knowledge, this is the first clinical trial to focus on PD-L1 expression in EGFR mutation-positive NSCLC. If the primary end point is met, combination therapy with erlotinib and ramucirumab could become a potential treatment option for this clinical population.

Automated summary

This study aims to evaluate the clinical efficacy of combining erlotinib and ramucirumab for the treatment of treatment-naive EGFR mutation-positive NSCLC with high PD-L1 expression.