title: 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.
abstract: We present the treatment rationale and study design for the RELAY study (NCT02411448 ). This phase Ib/III study will assess safety, tolerability, and efficacy of the combination of ramucirumab with erlotinib in previously untreated stage IV non-small-cell lung cancer patients with an activating epidermal growth factor receptor (EGFR) mutation.
  
  
  
  The study is being conducted in approximately 120 sites in North America, Europe, and Asia and is currently open for enrollment. In part A (phase Ib), approximately 12 patients will receive ramucirumab (10 mg/kg) every 2 weeks with erlotinib (150 mg) every day. Dose-limiting toxicity will be assessed during 2 cycles (4 weeks) of treatment. In part B (phase III), approximately 450 patients will be randomized in a 1:1 ratio to receive ramucirumab or placebo every 2 weeks with erlotinib daily until disease progression, unacceptable toxicity, or other withdrawal criteria are met. The primary end point is progression-free survival, on the basis of investigator assessment. Secondary end points include overall survival, objective response rate, disease control rate, duration of response, safety, and quality of life.
  
  
  
  Erlotinib with ramucirumab combination was chosen because the addition of an antiangiogenic agent, such as ramucirumab, would further improve the efficacy of erlotinib, which is a standard of care in the first-line treatment of patients with activating EGFR mutations.
authors.affiliation: David Geffen School of Medicine at UCLA, Los Angeles, CA.
authors.forename: Edward B
authors.initials: EB
authors.lastname: Garon
authors.affiliation: Lungen Clinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Reck
authors.affiliation: Hospital Doce de Octubre, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Paz-Ares
authors.affiliation: Hospital Doce de Octubre, Madrid, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Ponce
authors.affiliation: Hospital Virgen del Rocio, Sevilla, Spain.
authors.forename: Jesus Corral
authors.initials: JC
authors.lastname: Jaime
authors.affiliation: Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Juan
authors.affiliation: Institut Català d'Oncologia, L'Hospitalet, Barcelona, Spain.
authors.forename: Ernest
authors.initials: E
authors.lastname: Nadal
authors.affiliation: Eli Lilly and Company, Bridgewater, NJ.
authors.forename: Pablo
authors.initials: P
authors.lastname: Lee
authors.affiliation: Eli Lilly and Company, Bridgewater, NJ.
authors.forename: Rita
authors.initials: R
authors.lastname: Dalal
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Liu
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: Shuang
authors.initials: S
authors.lastname: He
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: Joseph
authors.initials: J
authors.lastname: Treat
authors.affiliation: Kinki University School of Medicine, Osaka, Japan. Electronic address: nakagawa@med.kindai.ac.jp.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D004311:Double-Blind Method; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007390:International Agencies; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D012107:Research Design; D055815:Young Adult; D000096662:Ramucirumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D066246:ErbB Receptors; D000069347:Erlotinib Hydrochloride; D000096662:Ramucirumab; C512478:EGFR protein, human
keywords: Epidermal growth factor receptor mutation; Erlotinib; Non-small cell lung cancer; RELAY trial; Ramucirumab