A Study of Ramucirumab (LY3009806) in Combination With Erlotinib in Previously Untreated Participants With EGFR Mutation-Positive Metastatic NSCLC (RELAY)
NCT ID: NCT02411448
Last Updated: 2026-01-16
Study Results
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View full resultsBasic Information
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ACTIVE_NOT_RECRUITING
PHASE3
545 participants
INTERVENTIONAL
2015-05-06
2026-12-31
Brief Summary
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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.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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Ramucirumab + Erlotinib
Part A: 10 milligrams per kilogram (mg/kg) ramucirumab administered every 2 weeks intravenously (IV) in combination with 150 mg erlotinib daily orally.
Participants may continue to receive treatment until discontinuation criteria are met.
Part B: 10 mg/kg ramucirumab administered every 2 weeks IV in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met.
Ramucirumab
Administered IV.
Erlotinib
Administered orally.
Placebo + Erlotinib
Part B: Placebo administered every 2 weeks IV in combination with 150 mg erlotinib daily orally.
Participants may continue to receive treatment until discontinuation criteria are met.
Placebo
Administered IV.
Erlotinib
Administered orally.
Ramucirumab + Gefitinib or Osimertinib
Part C: 10 mg/kg ramucirumab administered every 2 weeks intravenously (IV) + 250 mg Gefitinib or 80 mg Osimertinib daily orally.
* Ramucirumab and gefitinib administered during period 1.
* Ramucirumab and osimertinib administered during period 2.
Ramucirumab
Administered IV.
Gefitinib
Administered orally.
Osimertinib
Administered orally.
Interventions
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Ramucirumab
Administered IV.
Placebo
Administered IV.
Erlotinib
Administered orally.
Gefitinib
Administered orally.
Osimertinib
Administered orally.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Eligible for first-line treatment with erlotinib based on documented evidence of tumor harboring an activating EGFR mutation \[exon 19 deletion or exon 21 (L858R) substitution mutation\].
* Mandatory provision of adequate archived stage IV NSCLC tissue samples or tissue samples other than stage IV NSCLC may be acceptable (optional for part C).
* At least one measurable lesion.
* Life expectancy of at least 3 months.
Exclusion Criteria
* Known leptomeningeal carcinomatosis, uncontrolled/unstable spinal cord compression, or brain metastases.
* Serious illness or medical condition.
* Ongoing treatment with CYP3A4 inducers or strong inhibitors.
* Ongoing therapy with nonsteroidal anti-inflammatory drugs for more than 2 months.
* History of gross hemoptysis.
* Significant bleeding disorders.
* Radiologically documented evidence of major blood vessel invasion or encasement by cancer.
* Radiographic evidence of intratumor cavitation.
* History of gastrointestinal perforation within last 6 months.
* History of bowel obstruction, inflammatory enteropathy or extensive intestinal resection.
* History of any arterial thrombotic event within 6 months prior to enrollment.
* The participant has any known significant ophthalmologic abnormalities of the surface of the eye.
18 Years
ALL
No
Sponsors
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Eli Lilly and Company
INDUSTRY
Responsible Party
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Principal Investigators
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Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Role: STUDY_DIRECTOR
Eli Lilly and Company
Locations
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UCLA Hematology/Oncology - Santa Monica
Los Angeles, California, United States
St. Charles Health System
Denver, Colorado, United States
The Gastroenterology Group, P.C.
Honolulu, Hawaii, United States
Cancer Center of Kansas
Wichita, Kansas, United States
Queens Medical Associates
Fresh Meadows, New York, United States
Levine Cancer Institute
Charlotte, North Carolina, United States
AHN Allegheny General Hospital
Pittsburgh, Pennsylvania, United States
Cross Cancer Institute
Edmonton, Alberta, Canada
Hôpital Arnaud de Villeneuve - CHU Montpellier
Montpellier, Hérault, France
Chu Grenoble Alpes
La Tronche, Isère, France
Hopital Claude Huriez - CHU de Lille
Lille, Nord, France
Centre Hospitalier Universitaire de Poitiers
Poitiers, Vienne, France
Hôpital Européen Georges Pompidou
Paris, , France
Robert-Bosch-Krankenhaus
Gerlingen, Baden-Wurttemberg, Germany
Thoraxklinik Heidelberg gGmbH
Heidelberg, Baden-Wurttemberg, Germany
Klinikum Köln-Merheim
Cologne, North Rhine-Westphalia, Germany
Klinikum Chemnitz GmbH
Chemnitz, Saxony, Germany
Städtisches Krankenhaus Martha-Maria Halle-Dölau gGmbH
Halle, Saxony-Anhalt, Germany
LungenClinic Grosshansdorf
Großhansdorf, Schleswig-Holstein, Germany
Helios Klinikum Emil von Behring Berlin-Zehlendorf
Berlin, , Germany
Sotiria Thoracic Diseases Hospital of Athens
Athens, Attikí, Greece
Queen Mary Hospital
Hong Kong, , Hong Kong
Queen Elizabeth Hospital
Yau Ma Tei, , Hong Kong
Instituto Tumori Giovanni Paolo II
Bari, Apulia, Italy
Cro-Irccs
Aviano, Friuli Venezia Giulia, Italy
Azienda Sanitaria Ospedaliera S Luigi Gonzaga
Orbassano, Torino, Italy
IRCCS - AOU di Bologna
Bologna, , Italy
Ospedale San Raffaele
Milan, , Italy
Istituto Oncologico Veneto IRCCS
Padua, , Italy
Aichi Cancer Center Hospital
Nagoya, Aichi-ken, Japan
National Cancer Center Hospital East
Kashiwa, Chiba, Japan
Ehime University Hospital
Tōon, Ehime, Japan
Kurume University Hospital
Kurume, Fukuoka, Japan
National Hospital Organization Asahikawa Medical Center
Asahikawa, Hokkaido, Japan
Hyogo Cancer Center
Akashi, Hyōgo, Japan
Hyogo Prefectual Amagasaki General Medical Center
Amagashiki, Hyōgo, Japan
Himeji Medical Center
Himeji, Hyōgo, Japan
Foundation for Biomedical Research and innovation
Kobe, Hyōgo, Japan
Kobe City Medical Center General Hospital
Kobe, Hyōgo, Japan
Kanazawa University Hospital
Kanazawa, Ishikawa-ken, Japan
Kanagawa Cardiovascular and Respiratory Center
Yokohama, Kanagawa, Japan
Kanagawa Cancer Center
Yokohama, Kanagawa, Japan
Sendai Kousei Hospital
Sendai, Miyagi, Japan
Niigata Cancer Center Hospital
Niigata, Niigata, Japan
Osaka Habikino Medical Center
Habikino, Osaka, Japan
Kansai Medical University Hospital
Hirakata, Osaka, Japan
Kishiwada City Hospital
Kishiwada, Osaka, Japan
Kindai University Hospital- Osakasayama Campus
Ōsaka-sayama, Osaka, Japan
National Hospital Organization Kinki-Chuo Chest Medical Center
Sakai, Osaka, Japan
Saitama Prefectural Cancer Center
Ina-machi, Saitama, Japan
Shizuoka Cancer Center
Nakatogari, Shizuoka, Japan
Tokyo Met Cancer & Infectious Diseases Center Komagome Hp
Bunkyo-ku, Tokyo, Japan
National Cancer Center Hospital
Chuo-Ku, Tokyo, Japan
Japanese Foundation for Cancer Research
Koto, Tokyo, Japan
National Hospital Organization Yamaguchi Ube Medical Center
Ube, Yamaguchi, Japan
Chiba University Hospital
Chiba, , Japan
National Hospital Organization Kyushu Medical Center
Fukuoka, , Japan
National Hospital Organization Kyushu Cancer Center
Fukuoka, , Japan
Kyushu University Hospital
Fukuoka, , Japan
Kyoto University Hospital
Kyoto, , Japan
Nagasaki University Hospital
Nagasaki, , Japan
Niigata University Medical & Dental Hospital
Niigata, , Japan
Okayama University Hospital
Okayama, , Japan
Osaka City General Hospital
Osaka, , Japan
Osaka Medical Center for Cancer and Cardiovascular Diseases
Osaka, , Japan
Osaka City University Hospital
Osaka, , Japan
St. Lukes International Hospital
Tokyo, , Japan
Juntendo University Hospital
Tokyo, , Japan
Nippon Medical School Hospital
Tokyo, , Japan
Wakayama MedicaL University Hospital
Wakayama, , Japan
Institutul Oncologic
Bucharest, București, Romania
S.C. MedisProf SRL
Cluj-Napoca, Cluj, Romania
Chungbuk National University Hospital
Cheongju-si, Chungcheongbuk-do [Chungbuk], South Korea
Seoul National University Bundang Hospital
Seongnam, Kyǒnggi-do, South Korea
The Catholic University Of Korea St. Vincent's Hospital
Suwon, Kyǒnggi-do, South Korea
Ajou University Hospital
Suwon, Kyǒnggi-do, South Korea
Gyeongsang National University Hospital
Jinju, Kyǒngsangnam-do, South Korea
Asan Medical Center
Seoul, Seoul-teukbyeolsi [Seoul], South Korea
Samsung Medical Center
Seoul, Seoul-teukbyeolsi [Seoul], South Korea
The Catholic Univ. of Korea Seoul St. Mary's Hospital
Seoul, Seoul-teukbyeolsi [Seoul], South Korea
Korea University Guro Hospital
Seoul, Seoul-teukbyeolsi [Seoul], South Korea
Ulsan University Hospital
Ulsan, Ulsan-Kwangyǒkshi, South Korea
Hospital Universitari Vall d'Hebron
Barcelona, Barcelona [Barcelona], Spain
Instituto Catalan de Oncologia - Hospital Duran i Reynals
Hospitalet, Barcelona [Barcelona], Spain
Hospital Son Llatzer
Palma, Illes Balears [Islas Baleares], Spain
Hospital Universitario Quironsalud Madrid
Pozuelo de Alarcón, Madrid, Spain
Hospital Universitario 12 de Octubre
Madrid, Madrid, Comunidad de, Spain
Clinica Universitaria De Navarra
Pamplona, Navarre, Spain
Hospital Universitario Virgen del Rocio
Seville, , Spain
Hospital Universitario Virgen de Valme
Seville, , Spain
Hospital Universitari i Politecnic La Fe
Valencia, , Spain
Chang Gung Memorial Hospital at Kaohsiung
Kaohsiung Niao Sung Dist, Kaohsiung, Taiwan
E-DA Hospital
Kaohsiung City, , Taiwan
China Medical University Hospital
Taichung, , Taiwan
Taichung Veterans General Hospital
Taichung, , Taiwan
National Cheng-Kung University Hospital
Tainan, , Taiwan
National Taiwan University Hospital
Taipei, , Taiwan
MacKay Memorial Hospital
Taipei, , Taiwan
Taipei Veterans General Hospital
Taipei, , Taiwan
Ege Universitesi Hastanesi
Bornova, İzmir, Turkey (Türkiye)
Baskent University Dr. Turgut Noyan Research and Training Center
Adana, , Turkey (Türkiye)
Trakya University
Edirne, , Turkey (Türkiye)
İnönü Üniversitesi Turgut Özal Tıp Merkezi Eğitim ve Araştırma Hastanesi
Malatya, , Turkey (Türkiye)
Royal Marsden Hospital (Chelsea)
London, Kensington and Chelsea, United Kingdom
Charing Cross Hospital
Chelsea, London, United Kingdom
City Hospital, Nottingham University Hospitals
Nottingham, Nottinghamshire, United Kingdom
Countries
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References
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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.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol: Protocol I4T-MC-JVCY(f)
Document Type: Study Protocol: Protocol Addendum I4T-MC-JVCY(9)
Document Type: Statistical Analysis Plan
Related Links
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A Study of Ramucirumab (LY3009806) in Combination With Erlotinib in Participants With EGFR Mutation-Positive Metastatic NSCLC
Other Identifiers
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I4T-MC-JVCY
Identifier Type: OTHER
Identifier Source: secondary_id
2014-004824-22
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
15540
Identifier Type: -
Identifier Source: org_study_id
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