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

A Multicenter, Randomized, Double-Blind Study of Erlotinib in Combination With Ramucirumab or Placebo in Previously Untreated Patients With EGFR Mutation-Positive Metastatic Non-Small Cell Lung Cancer

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Placebo; Drug: Ramucirumab; Drug: Erlotinib; Drug: Gefitinib; Drug: Osimertinib

• Study Type: Interventional
• Enrollment (Actual): 545
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
• France
  • Paris, France, 75015
    • Hôpital Europeen Georges Pompidou
  • Hérault
    • Montpellier, Hérault, France, 34090
      • Hôpital Arnaud de Villeneuve - CHU Montpellier
  • Isère
    • La Tronche, Isère, France, 38700
      • Chu Grenoble Alpes
  • Nord
    • Lille, Nord, France, 59037
      • Hopital Claude Huriez - CHU de Lille
  • Vienne
    • Poitiers, Vienne, France, 86021
      • Centre Hospitalier Universitaire de Poitiers
• Germany
  • Berlin, Germany, 14165
    • Helios Klinikum Emil von Behring Berlin-Zehlendorf
  • Baden-Wurttemberg
    • Gerlingen, Baden-Wurttemberg, Germany, 70839
      • Robert-Bosch-Krankenhaus
    • Heidelberg, Baden-Wurttemberg, Germany, 69126
      • Thoraxklinik Heidelberg gGmbH
  • North Rhine-Westphalia
    • Cologne, North Rhine-Westphalia, Germany, 51109
      • Klinikum Köln-Merheim
  • Saxony
    • Chemnitz, Saxony, Germany, 09113
      • Klinikum Chemnitz GmbH
  • Saxony-Anhalt
    • Halle, Saxony-Anhalt, Germany, 06120
      • Städtisches Krankenhaus Martha-Maria Halle-Dölau gGmbH
  • Schleswig-Holstein
    • Großhansdorf, Schleswig-Holstein, Germany, 22927
      • LungenClinic Grosshansdorf
• Greece
  • Attikí
    • Athens, Attikí, Greece, 11527
      • Sotiria Thoracic Diseases Hospital of Athens
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Yau Ma Tei, Hong Kong, 999077
    • Queen Elizabeth Hospital
• Italy
  • Bologna, Italy, 40138
    • IRCCS - AOU di Bologna
  • Milan, Italy, 20132
    • Ospedale San Raffaele
  • Padua, Italy, 35128
    • Istituto Oncologico Veneto IRCCS
  • Apulia
    • Bari, Apulia, Italy, 70124
      • Instituto Tumori Giovanni Paolo II
  • Friuli Venezia Giulia
    • Aviano, Friuli Venezia Giulia, Italy, 33081
      • Cro-Irccs
  • Torino
    • Orbassano, Torino, Italy, 10043
      • Azienda Sanitaria Ospedaliera S Luigi Gonzaga
• Japan
  • Chiba, Japan, 260-8677
    • Chiba University Hospital
  • Fukuoka, Japan, 810-8563
    • National Hospital Organization Kyushu Medical Center
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Kyoto, Japan, 606-8507
    • Kyoto University Hospital
  • Nagasaki, Japan, 852-8501
    • Nagasaki University Hospital
  • Niigata, Japan, 951-8520
    • Niigata University Medical & Dental Hospital
  • Okayama, Japan, 700-8558
    • Okayama University Hospital
  • Osaka, Japan, 545-8586
    • Osaka City University Hospital
  • Osaka, Japan, 534-0021
    • Osaka City General Hospital
  • Osaka, Japan, 537-8511
    • Osaka Medical Center for Cancer and Cardiovascular Diseases
  • Tokyo, Japan, 113-8431
    • Juntendo University Hospital
  • Tokyo, Japan, 113-8603
    • Nippon Medical School Hospital
  • Tokyo, Japan, 104-8560
    • St. Lukes International Hospital
  • Wakayama, Japan, 641-0012
    • Wakayama Medical University Hospital
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 464-8681
      • Aichi Cancer Center Hospital
  • Chiba
    • Kashiwa, Chiba, Japan, 277 8577
      • National Cancer Center Hospital East
  • Ehime
    • Tōon, Ehime, Japan, 791-0295
      • Ehime University Hospital
  • Fukuoka
    • Kurume, Fukuoka, Japan, 830-0011
      • Kurume University Hospital
  • Hokkaido
    • Asahikawa, Hokkaido, Japan, 070-8644
      • National Hospital Organization Asahikawa Medical Center
  • Hyōgo
    • Akashi, Hyōgo, Japan, 673-8558
      • Hyogo Cancer Center
    • Amagashiki, Hyōgo, Japan, 660-8550
      • Hyogo Prefectual Amagasaki General Medical Center
    • Himeji, Hyōgo, Japan, 670-8520
      • Himeji Medical Center
    • Kobe, Hyōgo, Japan, 650-0047
      • Kobe City Medical Center General Hospital
    • Kobe, Hyōgo, Japan, 650-0047
      • Foundation for Biomedical Research and innovation
  • Ishikawa-ken
    • Kanazawa, Ishikawa-ken, Japan, 920-8641
      • Kanazawa University Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 241-8515
      • Kanagawa Cancer Center
    • Yokohama, Kanagawa, Japan, 236-0051
      • Kanagawa Cardiovascular and Respiratory Center
  • Miyagi
    • Sendai, Miyagi, Japan, 9800873
      • Sendai Kousei Hospital
  • Niigata
    • Niigata, Niigata, Japan, 951-8566
      • Niigata Cancer Center Hospital
  • Osaka
    • Habikino, Osaka, Japan, 583-8588
      • Osaka Habikino Medical Center
    • Hirakata, Osaka, Japan, 573-1191
      • Kansai Medical University Hospital
    • Kishiwada, Osaka, Japan, 596-8501
      • Kishiwada City Hospital
    • Sakai, Osaka, Japan, 5918555
      • National Hospital Organization Kinki-Chuo Chest Medical Center
    • Ōsaka-sayama, Osaka, Japan, 589-8511
      • Kindai University Hospital- Osakasayama Campus
  • Saitama
    • Ina-machi, Saitama, Japan, 362-0806
      • Saitama Prefectural Cancer Center
  • Shizuoka
    • Nakatogari, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8677
      • Tokyo Met Cancer & Infectious Diseases Center Komagome Hp
    • Chuo-Ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
    • Koto, Tokyo, Japan, 135-8550
      • Japanese Foundation for Cancer Research
  • Yamaguchi
    • Ube, Yamaguchi, Japan, 755-0241
      • National Hospital Organization Yamaguchi Ube Medical Center
• Romania
  • București
    • Bucharest, București, Romania, 022328
      • Institutul Oncologic
  • Cluj
    • Cluj-Napoca, Cluj, Romania, 400058
      • S.C. Medisprof SRL
• South Korea
  • Chungcheongbuk-do [Chungbuk]
    • Cheongju-si, Chungcheongbuk-do [Chungbuk], South Korea, 28644
      • Chungbuk National University Hospital
  • Kyǒnggi-do
    • Seongnam, Kyǒnggi-do, South Korea, 10408
      • Seoul National University Bundang Hospital
    • Suwon, Kyǒnggi-do, South Korea, 16499
      • Ajou University Hospital
    • Suwon, Kyǒnggi-do, South Korea, 16247
      • The Catholic University of Korea St. Vincent's Hospital
  • Kyǒngsangnam-do
    • Jinju, Kyǒngsangnam-do, South Korea, 52727
      • Gyeongsang National University Hospital
  • Seoul-teukbyeolsi [Seoul]
    • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 06591
      • The Catholic Univ. of Korea Seoul St. Mary's Hospital
    • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 06351
      • Samsung Medical Center
    • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 05505
      • Asan Medical Center
    • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 08308
      • Korea University Guro Hospital
  • Ulsan-Kwangyǒkshi
    • Ulsan, Ulsan-Kwangyǒkshi, South Korea, 44033
      • Ulsan University Hospital
• Spain
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Seville, Spain, 41014
    • Hospital Universitario Virgen de Valme
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Hospital Universitari Vall d'Hebron
    • Hospitalet, Barcelona [Barcelona], Spain, 08908
      • Instituto Catalan de Oncologia - Hospital Duran I Reynals
  • Illes Balears [Islas Baleares]
    • Palma, Illes Balears [Islas Baleares], Spain, 07198
      • Hospital Son Llatzer
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Hospital Universitario Quironsalud Madrid
  • Madrid, Comunidad de
    • Madrid, Madrid, Comunidad de, Spain, 28041
      • Hospital Universitario 12 de Octubre
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universitaria de Navarra
• Taiwan
  • Kaohsiung City, Taiwan, 82445
    • E-DA Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Tainan, Taiwan, 704
    • National Cheng-Kung University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 10449
    • Mackay Memorial Hospital
  • Kaohsiung
    • Kaohsiung Niao Sung Dist, Kaohsiung, Taiwan, 83301
      • Chang Gung Memorial Hospital at Kaohsiung
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 1250
    • Baskent University Dr. Turgut Noyan Research and Training Center
  • Edirne, Turkey (Türkiye), 22030
    • Trakya University
  • Malatya, Turkey (Türkiye), 44280
    • İnönü Üniversitesi Turgut Özal Tıp Merkezi Eğitim ve Araştırma Hastanesi
  • İzmir
    • Bornova, İzmir, Turkey (Türkiye), 35100
      • Ege Universitesi Hastanesi
• United Kingdom
  • Kensington and Chelsea
    • London, Kensington and Chelsea, United Kingdom, SW3 6JJ
      • Royal Marsden Hospital (Chelsea)
  • London
    • Chelsea, London, United Kingdom, W6 8RF
      • Charing Cross Hospital
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
      • City Hospital, Nottingham University Hospitals
• United States
  • California
    • Los Angeles, California, United States, 90404
      • UCLA Hematology/Oncology - Santa Monica
  • Colorado
    • Denver, Colorado, United States, 80203
      • St. Charles Health System
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • The Gastroenterology Group, P.C.
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas
  • New York
    • Fresh Meadows, New York, United States, 11366
      • Queens Medical Associates
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • AHN Allegheny General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Cytologically or histologically confirmed diagnosis of Stage IV NSCLC as defined by the American Joint Committee on Cancer Staging Criteria for Lung Cancer (AJCC 7th edition 2009).
• 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 T790M EGFR mutation (not applicable for Part C Period 2).
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Ramucirumab; Administered IV.; Other Names: LY3009806; Drug: Erlotinib; Administered orally.
Placebo Comparator: 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.	Drug: Placebo; Administered IV.; Drug: Erlotinib; Administered orally.
Experimental: 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.	Drug: Ramucirumab; Administered IV.; Other Names: LY3009806; Drug: Gefitinib; Administered orally.; Drug: Osimertinib; Administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part B: Progression Free Survival (PFS)	PFS is defined as the time from the date of randomization to the date of radiographically documented progressive disease (PD) based on investigator assessment, or the date of death due to any cause, whichever is first assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.	Randomization to Measured Progressive Disease or Death from Any Cause (Up To 37 Months)
Number of Participants With Treatment-Emergent Adverse Events	A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section.	Cycle 1 Day 1 through End of Study (Up To 3 Years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part B: Overall Survival (OS)	OS was defined as the time from the date of randomization to the date of death from any cause. For each participant who was not known to have died as of the data-inclusion cutoff date for a particular analysis,OS was censored for that analysis at the date of last contact prior to the data-inclusion cutoff date (contacts considered in the determination of last contact date include adverse event (AE) date, lesion assessment date, visit date, and last known alive date).	Randomization to Date of Death from Any Cause (Up To 37 Months)
Part B: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	ORR was defined as the percentage of randomized participants achieving a best overall response of partial response (PR) or complete response (CR) assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR was at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.	Randomization to Progressive Disease (Up To 37 Months)
Part B: Percentage of Participants With CR, PR, or Stable Disease (SD) (Disease Control Rate [DCR])	DCR was defined as the percentage of randomized participants achieving a best overall response of CR,PR, or stable disease(SD) assessed via Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1. CR was defined as the disappearance of all lesions,pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions.PR was at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters.SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease(PD) was at least a 20% increase in the sum of the diameters of target lesions,taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression.	Randomization to Progressive Disease (Up To 37 Months)
Part B: Duration of Response (DoR)	DoR was defined as the date of first documented CR or PR (responder) to the date of progressive disease or the date of death due to any cause, whichever was earlier. If a responder was not known to have died or have progressive disease, then the participant was censored at the date of last evaluable tumor assessment.CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR was at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.	Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Up To 37 Months)
Part B: Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab	Part B: Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab	Cycle 2 Day 1: Predose; Cycle 4 Day 1: Predose; Cycle 7 Day 1: Predose; Cycle 14 Day 1
Part B: Number of Participants With Anti-Ramucirumab Antibodies	Part B: Number of Participants With Anti-Ramucirumab Antibodies.	Cycle 1 Predose through Follow-up (Up To 37 Months)
Part B: Best Change From Baseline on the Lung Cancer Symptom Scale (LCSS)	The LCSS consisted of 9 items: 6 items focused on lung cancer symptoms [loss of appetite, fatigue, cough, dyspnea (shortness of breath), hemoptysis (blood in sputum), and pain] and 3 global items (symptom distress, interference with activity level, and global quality of life). Participant responses to each item were measured using visual analogue scales (VAS) with 100-millimeter (mm) lines. A higher score for any item represented a higher level of symptoms/problems. The LCSS total score was defined as the mean of all 9 items. Average symptom burden index (ASBI) was calculated as the mean of the six symptom-specific questions from the LCSS. Potential scores range from 0 (for best outcome) to 100 (for worst outcome).	Baseline, End of Study (Up To 37 Months)
Part B: Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score	The EQ-5D-5L is a standardized instrument used to measure self-reported health status of the participants. It consists of 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). There are 5 response levels (no problems, slight problems, moderate problems, severe problems, and extreme problems/unable to), ranging from 1 to 5 (good to bad). Dimension responses were converted to an index score using UK weights. The index scores were anchored on full health (1.0) to dead (0) with negative values assigned to health states considered worse than death.	Baseline, Cycle 10 (each cycle is 2 weeks)
Part B: Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score	The EQ-5D-5L is a standardized instrument used to measure self-reported health status of the participants. It consists of 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). There are 5 response levels (no problems, slight problems, moderate problems, severe problems, and extreme problems/unable to), ranging from 1 to 5 (good to bad). Dimension responses were converted to an index score using UK weights. The index scores were anchored on full health (1.0) to dead (0) with negative values assigned to health states considered worse than death.	Baseline, Cycle 28 (each cycle is 2 weeks)
Part B: Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score	The EQ-5D-5L is a standardized instrument used to measure self-reported health status of the participants. It consists of 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). There are 5 response levels (no problems, slight problems, moderate problems, severe problems, and extreme problems/unable to), ranging from 1 to 5 (good to bad). Dimension responses were converted to an index score using UK weights. The index scores were anchored on full health (1.0) to dead (0) with negative values assigned to health states considered worse than death.	Baseline, Cycle 40 (each cycle is 2 weeks)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: 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), Eli Lilly and Company

Publications and helpful links

General Publications

• 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, 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.
• 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.
• 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.
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Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2015
• Primary Completion (Actual): January 23, 2019
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 3, 2015
• First Submitted That Met QC Criteria: April 3, 2015
• First Posted (Estimated): April 8, 2015

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: December 24, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Proteins; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Quinazolines; Erlotinib Hydrochloride; Gefitinib; Ramucirumab; osimertinib
• Other Study ID Numbers: 15540; I4T-MC-JVCY (Other Identifier: Eli Lilly and Company); 2014-004824-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR