JTO Clinical and Research Reports (Apr 2022)

RELAY+: Exploratory Study of Ramucirumab Plus Gefitinib in Untreated Patients With EGFR-Mutated Metastatic NSCLC

  • Makoto Nishio, MD, PhD,
  • Kazuto Nishio, MD, PhD,
  • Martin Reck, MD, PhD,
  • Edward B. Garon, MD,
  • Fumio Imamura, MD, PhD,
  • Tomoya Kawaguchi, PhD,
  • Hiroyuki Yamaguchi, MD, PhD,
  • Satoshi Ikeda, MD, PhD,
  • Katsuya Hirano, MD,
  • Carla Visseren-Grul, MD,
  • Matteo Ceccarelli, PharmD, MS,
  • Sameera R. Wijayawardana, PhD,
  • Annamaria Zimmermann, MS,
  • Tomoko Matsui,
  • Sotaro Enatsu, MD, PhD,
  • Kazuhiko Nakagawa, MD, PhD

Journal volume & issue
Vol. 3, no. 4
p. 100303

Abstract

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Introduction: Ramucirumab (RAM) plus erlotinib was found to have superior progression-free survival (PFS) versus placebo plus erlotinib in untreated EGFR-mutated metastatic NSCLC in the global phase 3 RELAY study. RELAY+ was an open-label, two-period, single-arm, exploratory study of RAM plus gefitinib (GEF; period 1) and RAM plus osimertinib (period 2) in East Asia (NCT02411448). Methods: Period 1 evaluated RAM (10 mg/kg) plus GEF (250 mg/d) in patients with untreated EGFR-mutated metastatic NSCLC. Period 2 evaluated RAM plus osimertinib (80 mg/d) in patients with disease progression who acquired T790M mutation in period 1. Exploratory end points included 1-year PFS rate (primary), other efficacy parameters, safety, and biomarker analyses of plasma (baseline, on-treatment, follow-up) using next-generation sequencing. Results: From December 2017 to August 2018, a total of 82 patients were enrolled and started treatment (period 1, RAM + GEF). The 1-year PFS rate was 62.9% (95% confidence interval: 50.3–73.1). Treatment-emergent adverse events of grade three or higher were reported with RAM plus GEF in 60 of 82 patients (73.2%; five patients [6.1%] grade four). There were two deaths owing to adverse events that occurred (acute cardiac failure, congestive cardiac failure). T790M rate at disease progression in plasma was 81.0% (13 of 16 patients). Conclusions: RELAY+ was found to have a favorable benefit–risk profile for RAM plus GEF in first-line treatment of East Asian patients with EGFR-mutated NSCLC.

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