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

Abstract

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.

Keywords: East Asia; Japan; Plasma biopsy; Treatment outcome; Vascular endothelial growth factor receptor-2.

Figure 1

RELAY+ exploratory open-label cohort: (A) study design and (B) patient disposition. ^aThe exploratory cohort included patients enrolled in Japan, South Korea, and Taiwan. ^bDeath due to adverse event. One patient died due to acute cardiac failure and one patient died due to congestive cardiac failure. Both events were considered related to the study treatment. Data cutoff date: November 25, 2020. GEF, gefitinib; ITT, intent-to-treat; OSI, osimertinib; q2w, once every 2 weeks; RAM, ramucirumab.

Figure 2

Swimmer plot of treatment sequence for (A) Japanese patients and (B) non-Japanese patients (RELAY+ period 1 ITT population). EGFR-Other = gefitinib, erlotinib, or afatinib as postdiscontinuation treatment; Chemo-ICI = chemotherapy/immunotherapy/PD-(L)1 inhibitor; EGFR-OSI = osimertinib; P2-OSI = osimertinib received in period 2; P2-RAM = ramucirumab received in period 2; VEGF-RAM = ramucirumab as postdiscontinuation treatment. Chemo, chemotherapy; GEF, gefitinib; ICI, immune checkpoint inhibitor; ITT, intent-to-treat; OSI, osimertinib; P2, period 2; PD, progressive disease; PD-(L)1, programmed death-(ligand) 1; RAM, ramucirumab; VEGF, vascular endothelial growth factor.

Figure 3

Kaplan-Meier plot of investigator-assessed 1-year PFS rate (period 1 ITT population). CI, confidence interval; ex19del, in-frame deletions of exon 19; ex21.L858R, L858R point mutation in exon 21; GEF, gefitinib; ITT, intent-to-treat; PFS, progression-free survival; RAM, ramucirumab.