A Phase 2, Study of Ficlatuzumab Plus Erlotinib vs. Placebo Plus Erlotinib in Subjects With Previously Untreated Metastatic, EGFR-mutated NSCLC and BDX004 Positive Label (FOCAL)

A Phase 2, Multicenter, Randomized, Double-blind Study of Ficlatuzumab Plus Erlotinib Versus Placebo Plus Erlotinib in Subjects Who Have Previously Untreated Metastatic, EGFR-mutated Non-small Cell Lung Cancer (NSCLC) and BDX004 Positive Label

Phase 2 multicenter, controlled, randomized, double-blind study to evaluate the efficacy and safety of ficlatuzumab versus placebo when administered with erlotinib in subjects with previously untreated metastatic EGFR-mutated NSCLC and BDX004 Positive Label.

Study Overview

• Status: Terminated
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: placebo; Drug: Erlotinib; Drug: Ficlatuzumab

Detailed Description

This is a Phase 2 multicenter, controlled, randomized, double-blind study to evaluate the efficacy and safety of ficlatuzumab versus placebo when administered with erlotinib in subjects with previously untreated metastatic EGFR-mutated NSCLC and BDX004 Positive Label.

Prior to screening, subjects will have tested positive for a sensitizing EGFR mutation to determine eligibility for treatment with erlotinib. During screening, subject serum samples will be tested using the investigational companion diagnostic (BDX004) test. Only those subjects who have a BDX004 Positive Label will be enrolled. Subject randomization will be stratified by EGFR mutation type and smoking status (ever versus never smokers). Subjects will be designated as never smokers if they have smoked less than 100 cigarettes in their lifetime. Radiographic tumor assessment, to include CT or MRI of chest and abdomen, will be performed every 4 weeks for the first 8 cycles, and every 8 weeks thereafter, using the same imaging modality per subject. Safety assessments will be performed on an ongoing basis.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse
    • Coffs Harbour, New South Wales, Australia, 2450
      • North Coast Cancer Institute
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
  • Queensland
    • Douglas, Queensland, Australia, 4814
      • Townsville Hospital
    • Southport, Queensland, Australia, 4215
      • ICON Cancer Care
    • Wolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Bedford Park, South Australia, Australia, 5043
      • Flinders Medical Centre
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Eastern Health
    • Frankston, Victoria, Australia, 3199
      • Frankston Hospital
    • Wendouree, Victoria, Australia, 3355
      • Ballarat Oncology and Haematology
• Hong Kong
  • Pok Fu Lam, Hong Kong
    • Queen Mary Hospital
  • N.T
    • Tuen Mun, N.T, Hong Kong
      • Tuen Mun Hospital
• Italy
  • Benevento, Italy, 82100
    • AO G.Rummo
  • Bologna, Italy, 40138
    • Policlinico S.Orsola Malpighi
  • Cremona, Italy, 26100
    • Istituti Ospitalieri di Cremona - Oncologia
  • Lucca, Italy, 55100
    • U.O.C. Oncologia
  • Milano, Italy, 20132
    • IRCCS Ospedale S.Raffaele
  • Pavia, Italy, 27100
    • Fondazione Salvatore Maugeri
  • Rozzano MI, Italy, 20089
    • IRCCS Istituto Clinico Humanitas
  • Treviglio BG, Italy, 24047
    • Ospedale Treviglio-Caravaggio
• Korea, Republic of
  • Chungcheongbuk-do, Korea, Republic of, 362-711
    • Chungbuk National University Hospital
  • Jeonnam, Korea, Republic of, 519-763
    • Chonnam National University Hwasun Hospital
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital, Yonsei Uni
  • Seoul
    • Guro-gu, Seoul, Korea, Republic of, 152703
      • Korea University Guro Hospital
• Singapore
  • Central Singapore, Singapore, 308433
    • John Hopkins Singapore International Medical Center
  • Singapore, Singapore, 169610
    • National Cancer Centre
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taichung, Taiwan, 40201
    • Chung Shan Medical University
  • Tainan, Taiwan, 70403
    • National Cheng Kung University
  • Taipei, Taiwan, 11696
    • Taipei Medical University
  • Taipei City, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei City, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taoyuan City, Taiwan, 333
    • Chang Gung Medical Foundation
• United States
  • California
    • Fresno, California, United States, 93701
      • UCSF Fresno
    • Redondo Beach, California, United States, 90277
      • Torrance Memorial Medical Center
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Boca Raton Regional Hospital Lynn Cancer Institute
    • Deerfield Beach, Florida, United States, 33442
      • University of Miami Sylvester Comprehensive Cancer Center Deerfield Beach
  • Hawaii
    • Honolulu, Hawaii, United States, 96819
      • Kaiser Permanente Hawaii
  • Louisiana
    • Lafayette, Louisiana, United States, 70503
      • Cancer Center of Acadiana
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New Jersey
    • Paramus, New Jersey, United States, 07652
      • Valley Medical Group
  • New York
    • Jamaica, New York, United States, 11432
      • Queens Hospital Cancer Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center
    • Canton, Ohio, United States, 44710
      • Aultman Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Cancer Center Cancer
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

• Histologically and/or cytologically confirmed primary diagnosis of Stage IV NSCLC (according to American Joint Committee on Cancer [AJCC] 7th edition lung cancer staging criteria).
• Measurable disease according to RECIST v.1.1.
• An EGFR exon 19 deletion and/or an exon 21 (L858R) substitution mutation.
• BDX004 Positive Label.
• Have received no prior systemic chemotherapy, immunotherapy, targeted therapy, or biologic therapy for metastatic NSCLC. Subjects may have previously been treated with postoperative adjuvant chemotherapy for early stage lung cancer or chemo radiotherapy for locally advanced disease provided this was completed at least 6 months prior to enrollment. No prior EGFR TKI therapy is allowed for any stage of NSCLC.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Exclusion Criteria
• History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agent or erlotinib.
• History of known brain metastases.
• Prior treatment with any other investigational drug or biologic agent within 5 half lives prior to randomization, or any investigational device within 2 weeks prior to randomization.
• Any unresolved toxicity from previous radiation therapy.

• Significant cardiovascular disease, including:

  • Echocardiogram (ECHO) or multiple gated acquisition (MUGA) showing left ventricular ejection fraction of less than 55%.
  • Cardiac failure New York Heart Association class III or IV.
  • Myocardial infarction, severe or unstable angina within 6 months prior to randomization.
  • History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation).
  • Significant thrombotic or embolic events within 3 months prior to randomization (significant thrombotic or embolic events include but are not limited to stroke or transient ischemic attack).
  • Any uncontrolled or severe cardiovascular disease.
• History of prior malignancy within 3 years prior to randomization (except for adequately treated non-melanoma skin cancer, carcinoma in situ of the breast or cervix, superficial bladder cancer, or early stage prostate cancer, without evidence of recurrence).
• Radiographic evidence of interstitial lung disease.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ficlatuzumab plus erlotinib; 150 mg Erlotinib orally once daily starting on Day 1 of Cycle 1 with 20 mg/kg Ficlatuzumab administered intravenously once every 2 weeks on Day 1 and Day 15 of each 28 day cycle.	Drug: Erlotinib; Other Names: Erlotinib hydrochloride; Drug: Ficlatuzumab; Other Names: Ficla
Active Comparator: Placebo plus erlotinib; 150 mg Erlotinib orally once daily starting on Day 1 of Cycle 1 with Placebo administered intravenously once every 2 weeks on Day 1 and Day 15 of each 28 day cycle.	Drug: placebo; Drug: Erlotinib; Other Names: Erlotinib hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Progression Free Survival is defined as the time from the date of randomization to the date of the first objective documentation of radiographic disease progression or death due to any cause, whichever occurs first.	Approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	To evaluate Safety and tolerability of ficlatuzumab plus erlotinib versus placebo plus erlotinib in subjects who have previously untreated metastatic EGFR-mutated NSCLC and a BDX004 Positive Label.	Approximately 24 months

Collaborators and Investigators

• Sponsor: AVEO Pharmaceuticals, Inc.
• Collaborators: Biodesix, Inc.
• Investigators: Study Director: Michael N Needle, MD, AVEO Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2014
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: December 9, 2014
• First Submitted That Met QC Criteria: December 12, 2014
• First Posted (Estimate): December 17, 2014

Study Record Updates

• Last Update Posted (Actual): October 22, 2020
• Last Update Submitted That Met QC Criteria: October 20, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: AV-299-14-206

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO