A Study of Ramucirumab (LY3009806) in Combination With Erlotinib in Previously Untreated Participants With EGFR Mutation-Positive Metastatic NSCLC (RELAY)

Summary

The main purpose of this study is to evaluate the efficacy and safety of ramucirumab in combination with erlotinib as compared to placebo in combination with erlotinib in previously untreated participants with stage IV non-small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation (Exon 19-Del and Exon 21 L858R). Safety and tolerability of ramucirumab in combination with erlotinib will be assessed in Part A before proceeding to Part B. The purpose of Part C is to determine the efficacy and safety of ramucirumab in combination with gefitinib in previously untreated East Asian participants with EGFR mutation-positive metastatic NSCLC and of ramucirumab in combination with osimertinib in those participants whose disease progressed on ramucirumab and gefitinib and that have T790M - positive metastatic NSCLC.

Timeline

Start

2015-05-06

Primary completion

2019-01-23

Completion

2026-12

Publications

• Nishino K, Seto T, Nishio M, Nishio K, Kasahara K, Satouchi M, Yoh K, Hayashi H, Enatsu S, Matsui T, Varughese SC, Visseren-Grul C, Nakagawa K. RELAY: safety and efficacy of ramucirumab plus erlotinib in elderly Japanese patients with metastatic EGFR-mutated NSCLC. Future Oncol. 2025 Oct;21(24):3197-3206. doi: 10.1080/14796694.2025.2560225. Epub 2025 Sep 25.
• Nishio M, Seto T, Reck M, Garon EB, Nishio K, Kasahara K, Nishino K, Satouchi M, Yoh K, Hayashi H, Sakai K, Enatsu S, Frimodt-Moller B, Matsui T, Varughese SC, Carlsen M, Visseren-Grul C, Nakagawa K. Final Survival Outcomes With Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib in Patients With Untreated EGFR-Mutated Metastatic NSCLC: RELAY Japanese Subset. JTO Clin Res Rep. 2025 Feb 28;6(6):100819. doi: 10.1016/j.jtocrr.2025.100819. eCollection 2025 Jun.
• Nakagawa K, Garon EB, Seto T, Nishio M, Aix SP, Paz-Ares L, Chiu CH, Park K, Novello S, Nadal E, Nishino K, Yoh K, Shih JY, Chik JYK, Moro-Sibilot D, Puri T, Chacko Varughese S, Frimodt-Moller B, Visseren-Grul C, Reck M. RELAY: Final Overall Survival for Erlotinib Plus Ramucirumab or Placebo in Untreated, EGFR-Mutated Metastatic NSCLC. J Thorac Oncol. 2025 Apr;20(4):487-499. doi: 10.1016/j.jtho.2024.11.032. Epub 2024 Nov 30.
• Nishio K, Sakai K, Nishio M, Seto T, Visseren-Grul C, Carlsen M, Matsui T, Enatsu S, Nakagawa K. Impact of ramucirumab plus erlotinib on circulating cell-free DNA from patients with untreated metastatic non-small cell lung cancer with EGFR-activating mutations (RELAY phase 3 randomized study). Transl Lung Cancer Res. 2023 Aug 30;12(8):1702-1716. doi: 10.21037/tlcr-22-736. Epub 2023 Aug 10.
• Garon EB, Reck M, Nishio K, Heymach JV, Nishio M, Novello S, Paz-Ares L, Popat S, Aix SP, Graham H, Butts BD, Visseren-Grul C, Nakagawa K; RELAY study investigators. Ramucirumab plus erlotinib versus placebo plus erlotinib in previously untreated EGFR-mutated metastatic non-small-cell lung cancer (RELAY): exploratory analysis of next-generation sequencing results. ESMO Open. 2023 Aug;8(4):101580. doi: 10.1016/j.esmoop.2023.101580. Epub 2023 Jun 28.
• Chiu CH, Lin MC, Wei YF, Chang GC, Su WC, Hsia TC, Su J, Wang AK, Jen MH, Puri T, Shih JY. Efficacy and Tolerability of Ramucirumab Plus Erlotinib in Taiwanese Patients with Untreated, Epidermal Growth Factor Receptor-Mutated, Stage IV Non-small Cell Lung Cancer in the RELAY Study. Target Oncol. 2023 Jul;18(4):505-515. doi: 10.1007/s11523-023-00975-5. Epub 2023 Jun 17.
• Nakagawa K, Garon EB, Gao L, Callies S, Zimmermann A, Walgren R, Visseren-Grul C, Reck M. RELAY, ramucirumab plus erlotinib versus placebo plus erlotinib in untreated EGFR-mutated metastatic non-small cell lung cancer: exposure-response relationship. Cancer Chemother Pharmacol. 2022 Aug;90(2):137-148. doi: 10.1007/s00280-022-04447-x. Epub 2022 Jul 16.
• Nishio M, Nishio K, Reck M, Garon EB, Imamura F, Kawaguchi T, Yamaguchi H, Ikeda S, Hirano K, Visseren-Grul C, Ceccarelli M, Wijayawardana SR, Zimmermann A, Matsui T, Enatsu S, Nakagawa K. RELAY+: Exploratory Study of Ramucirumab Plus Gefitinib in Untreated Patients With EGFR-Mutated Metastatic NSCLC. JTO Clin Res Rep. 2022 Feb 26;3(4):100303. doi: 10.1016/j.jtocrr.2022.100303. eCollection 2022 Apr.
• Nadal E, Horinouchi H, Shih JY, Nakagawa K, Reck M, Garon EB, Wei YF, Kollmeier J, Frimodt-Moller B, Barrett E, Lipkovich O, Visseren-Grul C, Novello S. RELAY, Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib in Patients with Untreated, Epidermal Growth Factor Receptor Mutation-Positive, Metastatic Non-Small-Cell Lung Cancer: Safety Profile and Manageability. Drug Saf. 2022 Jan;45(1):45-64. doi: 10.1007/s40264-021-01127-2. Epub 2021 Dec 20.
• Mitani S, Chen Y, Inoue K, Mori J, Gao L, Long A, Wakabayashi S. Clinical Impact of a Shortened Infusion Duration of Ramucirumab in Japanese Patients -A Model-Based Approach. Gan To Kagaku Ryoho. 2021 Nov;48(11):1381-1387.
• Nakagawa K, Garon EB, Seto T, Nishio M, Ponce Aix S, Paz-Ares L, Chiu CH, Park K, Novello S, Nadal E, Imamura F, Yoh K, Shih JY, Au KH, Moro-Sibilot D, Enatsu S, Zimmermann A, Frimodt-Moller B, Visseren-Grul C, Reck M; RELAY Study Investigators. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Dec;20(12):1655-1669. doi: 10.1016/S1470-2045(19)30634-5. Epub 2019 Oct 4.
• Reck M, Garon EB, Paz-Ares L, Ponce S, Jaime JC, Juan O, Nadal E, Kiura K, Widau RC, He S, Dalal R, Lee P, Nakagawa K. Randomized, Double-Blind Phase Ib/III Study of Erlotinib With Ramucirumab or Placebo in Previously Untreated EGFR-Mutant Metastatic Non-Small-Cell Lung Cancer (RELAY): Phase Ib Results. Clin Lung Cancer. 2018 May;19(3):213-220.e4. doi: 10.1016/j.cllc.2017.11.003. Epub 2017 Nov 21.
• Garon EB, Reck M, Paz-Ares L, Ponce S, Jaime JC, Juan O, Nadal E, Lee P, Dalal R, Liu J, He S, Treat J, Nakagawa K. Treatment Rationale and Study Design for the RELAY Study: A Multicenter, Randomized, Double-Blind Study of Erlotinib With Ramucirumab or Placebo in Patients With Epidermal Growth Factor Receptor Mutation-Positive Metastatic Non-Small-Cell Lung Cancer. Clin Lung Cancer. 2017 Jan;18(1):96-99. doi: 10.1016/j.cllc.2016.05.023. Epub 2016 Jun 8.

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