A Study of LY2875358 in Participants With Non-Small Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations (Balise)

A Randomized, Controlled Phase 2 Study Evaluating LY2875358 Plus Erlotinib Versus Erlotinib as First-Line Treatment in Metastatic Non-Small Cell Lung Cancer Patients With Activating EGFR Mutations Who Have Disease Control After an 8-Week Lead-In Treatment With Erlotinib

The primary purpose of this study is to compare the efficacy of the study drug LY2875358, given together with erlotinib, against erlotinib, alone. Participants will have Non-Small Cell Lung Cancer (NSCLC) that has advanced to Stage IV. Participants should not have been treated with drugs for Stage IV NSCLC, previously. All participants will get erlotinib alone, for approximately 8 weeks. Participants with radiographic disease control at the end of the erlotinib lead-in study period will be randomly assigned to receive LY2875358 plus erlotinib or erlotinib alone. Participants, who were chosen to receive erlotinib, alone, may cross over to the combination treatment at the time of progression.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Erlotinib; Biological: LY2875358

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Capital Region
    • Herlev, Capital Region, Denmark, 2730
      • Herlev and Gentofte Hospital
  • Copenhagen
    • Copenhagen, Copenhagen, Denmark, 2100
      • Rigshospitalet
  • Syd
    • Odense C, Syd, Denmark, 5000
      • Odense Universitetshospital
• France
  • Caen, France, 14033
    • CHU de Caen Hopital Cote de Nacre
  • Clermont-Ferrand, France, 63000
    • Chu Gabriel Montpied
  • Grenoble, France, 38043
    • CHU de Grenoble Hopital Albert Michallon
  • Lyon (Bron) Cedex, France, 69677
    • HCL-Hôpital Louis Pradel
  • Montpellier, France, 34295
    • Hôpital Arnaud de Villeneuve - CHU Montpellier
  • Poitiers, France, 86021
    • Chu La Miletrie
• Germany
  • Berlin, Germany, 14165
    • Helios Klinikum Emil von Behring Berlin-Zehlendorf
  • Baden-Wurttemberg
    • Gerlingen, Baden-Wurttemberg, Germany, 70839
      • Klinik Schillerhöhe
    • Heidelberg, Baden-Wurttemberg, Germany, 69126
      • Thoraxklinik-Heidelberg gGmbH
    • Ulm, Baden-Wurttemberg, Germany, 89075
      • Universitatsklinikum Ulm
  • North Rhine-Westphalia
    • Cologne, North Rhine-Westphalia, Germany, 51109
      • Klinikum Köln-Merheim
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany, 23538
      • Universitätsklinikum Schleswig-Holstein
• Italy
  • Bari, Italy, 70124
    • Istituto Tumori ""Giovanni Paolo II
  • Cremona, Italy, 26100
    • Istituti Ospedalieri di Cremona
  • Florence
    • Florence, Florence, Italy, 50134
      • Azienda Ospedaliera Universitaria Careggi
  • Torino
    • Orbassano, Torino, Italy, 10043
      • Azienda Sanitaria Ospedaliera S Luigi Gonzaga
  • Veneto
    • Padua, Veneto, Italy, 35128
      • Istituto Oncologico Veneto IRCCS
• Netherlands
  • Arnhem, Netherlands, 6815 AD
    • Ziekenhuis Rijnstate
  • Harderwijk, Netherlands, 3844 DG
    • Ziekenhuis St. Jansdal
  • Nieuwegein, Netherlands, 3435 CM
    • St. Antonius Ziekenhuis, locatie Nieuwegein
  • North Brabant
    • 's-Hertogenbosch, North Brabant, Netherlands, 5223 GZ
      • Jeroen Bosch Hospital
• South Korea
  • Chungcheongbuk-do [Chungbuk]
    • Cheongju-si, Chungcheongbuk-do [Chungbuk], South Korea, 28644
      • Chungbuk National University Hospital
  • Incheon-gwangyeoksi [Incheon]
    • Namdong-gu, Incheon-gwangyeoksi [Incheon], South Korea, 21565
      • Gachon University Gil Medical Center
  • Korea
    • Seoul, Korea, South Korea, 03722
      • Severance Hospital, Yonsei University Health System
  • Kyǒnggi-do
    • Seongnam, Kyǒnggi-do, South Korea, 13620
      • Seoul National University Bundang Hospital
  • Seoul-teukbyeolsi [Seoul]
    • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 06351
      • Samsung Medical Center
    • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 05505
      • Asan Medical Center
  • Ulsan-Kwangyǒkshi
    • Ulsan, Ulsan-Kwangyǒkshi, South Korea, 44033
      • Ulsan University Hospital
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Corporacion Sanitaria Parc Tauli
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Puerta de Hierro
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Hospital Universitario Quirónsalud Madrid
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universitaria de Navarra
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
• United Kingdom
  • Oxford, United Kingdom, OX3 7LJ
    • Churchill Hospital
  • Glasgow City
    • Glasgow, Glasgow City, United Kingdom, g12OYN
      • Gartnavel General Hospital
  • London
    • Chelsea, London, United Kingdom, W6 8RF
      • Charing Cross Hospital
  • Manchester
    • Wythenshawe, Manchester, United Kingdom, M23 9LT
      • Wythenshawe Hospital
  • West Midlands
    • Wolverhampton, West Midlands, United Kingdom, WV10 0QP
      • New Cross Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of metastatic Stage IV NSCLC
• Have at least 1 measurable lesion whose presence is assessable using standard techniques by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1)
• Have molecular evidence of an epidermal growth factor receptor mutation (EGFRmt) known to be associated with EGFR tyrosine kinase inhibitor (TKI) drug sensitivity (G719X, exon 19 deletion, L858R, L861Q)
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Haven't received any prior systemic chemotherapy for Stage IV NSCLC (unless received as neoadjuvant or adjuvant therapy for early-stage NSCLC disease and completed therapy at least 6 months prior to enrollment)
• Availability of adequate tumor material (block or slides)

Exclusion Criteria:

• Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or non-approved use of a drug or device
• Have previously completed or withdrawn from this study or any other study investigating LY2875358
• Have a serious concomitant systemic disorder or significant cardiac disease
• Have interstitial pneumonia or interstitial fibrosis of the lung or have pleural effusion, pericardial fluids or ascites, requiring drainage every other week or more frequently
• Have a history of another malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to the study
• Have major surgery less than 2 weeks prior to the initiation of study treatment therapy
• Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY2875358 plus Erlotinib; Lead In: Approximately 8 weeks of erlotinib 150 milligram (mg) given orally per day. Randomization: Erlotinib 150 mg given orally per day plus 750 mg LY2875358 given as 1.5 hours intravenous (IV) infusions on Days 1 and 15 of 28-day cycles.	Drug: Erlotinib; Administered Orally; Biological: LY2875358; Administered IV
Active Comparator: Erlotinib; Lead In: Approximately 8 weeks of erlotinib 150 mg given orally per day. Randomization: Continue Erlotinib 150 mg given orally per day, in 28-day cycles.	Drug: Erlotinib; Administered Orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression Free Survival (PFS)	Randomization to Objective Disease Progression or Death Due to Any Cause (Estimated 3 Years)

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Tumor Size (CTS)	Baseline to Measurement with Smallest Tumor Size (Estimated 3 Years)
Proportion of Participants Exhibiting a Confirmed Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])	Baseline to Objective Disease Progression or Start of New Anticancer Therapy (Estimated 3 Years)
Duration of Response (DoR)	Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Estimated 3 Years)
Time to Progressive Disease (TTPD)	Randomization to Objective Disease Progression (Estimated 3 Years)
Proportion of Participants Exhibiting a Stable Disease (SD) or a confirmed CR or PR (Disease Control Rate [DCR])	Baseline to Objective Disease Progression or Participant Stops Study (Estimated 3 Years)
Overall Survival (OS)	Randomization to Death Due to Any Cause (Estimated 5 Years)
Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ) C30 (QLQ-C30) and Lung Cancer 13 (QLQ-LC13)	Baseline, Objective Disease Progression or Participants Stops Study (Estimated 3 Years)
Pharmacokinetics (PK): Area Under the Concentration Time Curve During a Dosing Interval (AUCtau) of LY2875358 and Erlotinib	Baseline through Cycle 4 (28 Day Cycle)
Proportion of Participants with Anti-LY2875358 Antibody Response	Baseline through 30 Day Follow Up (Estimated 3 Years)

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

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2013
• Primary Completion (Actual): March 14, 2016
• Study Completion (Actual): January 8, 2026

Study Registration Dates

• First Submitted: July 9, 2013
• First Submitted That Met QC Criteria: July 11, 2013
• First Posted (Estimated): July 12, 2013

Study Record Updates

• Last Update Posted (Actual): January 26, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: January 1, 2026

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; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinazolines; Erlotinib Hydrochloride; emibetuzumab
• Other Study ID Numbers: 14209; I4C-MC-JTBB (Other Identifier: Eli Lilly and Company); 2024-514268-18-00 (Ctis)

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 European Union (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