Study of Patritumab in Combination With Erlotinib in Subjects With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC). (HER3-Lung) (HER3-Lung)

Phase 3, Randomized, Placebo-Controlled, Double-Blind, Multi-Center, Two-Part Study of Patritumab (U3-1287) In Combination With Erlotinib in EGFR Wild-type Subjects With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) Who Have Progressed on at Least One Prior Systemic Therapy

1. Part A: Subjects will receive Patritumab or placebo with erlotinib. Progression-free survival will be the primary outcome. Subjects will need to have Epidermal Growth Factor Receptor (EGFR) wild-type, locally advance or metastatic NSCLC and have their cancer progressed after at least one prior systemic anti-cancer therapy, available recent or archival tumor specimen and may not have had previous EGFR-targeted regimen, anti-HER2 (Human Epidermal Growth Factor Receptor 2), anti-HER3, or anti-HER4 therapy. Subjects may have high heregulin or low heregulin.
2. Part B: Subjects will receive Patritumab or placebo with erlotinib. Overall survival will be the primary outcome. Subjects will need to have EGFR wild-type, locally advance or metastatic NSCLC and have their cancer progressed after at least one prior systemic anti-cancer therapy, available recent or archival tumor specimen and may not have had previous EGFR-targeted regimen, anti-HER2, anti-HER3, or anti-HER4 therapy. Only subjects with high heregulin will be enrolled.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 145
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Charleroi, Belgium
  • Gent, Belgium, 9000
  • Liege, Belgium
  • Yvoir, Belgium, 5530
  • Antwerpen
    • Brasschaat, Antwerpen, Belgium
  • Brussels
    • Bruxelles, Brussels, Belgium
  • Hainaut
    • Charleroi, Hainaut, Belgium
• Canada
  • Ontario
    • Hamilton, Ontario, Canada
    • Kingston, Ontario, Canada
    • Toronto, Ontario, Canada
  • Quebec
    • Levis, Quebec, Canada
    • Montreal, Quebec, Canada
• Czechia
  • Ostava-Poruba, Czechia
  • Ostrava-Poruba, Czechia
• Germany
  • Gießen, Germany
  • Baden-Wurttemberg
    • Esslingen am Neckar, Baden-Wurttemberg, Germany
    • Gerlingen, Baden-Wurttemberg, Germany
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany
    • Ulm, Baden-Württemberg, Germany
    • Villingen-Schwenningen, Baden-Württemberg, Germany
  • Bayern
    • Gauting, Bayern, Germany, 82131
    • Muenchen, Bayern, Germany
  • Hessen
    • Frankfurt am Main, Hessen, Germany
    • Immenhausen, Hessen, Germany
  • Nordrhein-Westfalen
    • Koln, Nordrhein-Westfalen, Germany
    • Rheine, Nordrhein-Westfalen, Germany
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany
  • Sachsen-Anhalt
    • Halle, Sachsen-Anhalt, Germany
  • Schleswig-Holstein
    • Grosshansdorf, Schleswig-Holstein, Germany
• Hungary
  • Tatabanya, Hungary
  • Fejer
    • Szekesfehervar, Fejer, Hungary
  • Gyor-Moson-Sopron
    • Gyor, Gyor-Moson-Sopron, Hungary
  • Jasz-Nagykun-Szolnok
    • Szolnok, Jasz-Nagykun-Szolnok, Hungary
• Italy
  • Benevento, Italy
  • Bologna, Italy
  • Cremona, Italy
  • Faenza, Italy
  • Genova, Italy
  • Milano, Italy
  • Napoli, Italy
  • Perugia, Italy
  • Ravenna, Italy
  • Rimini, Italy
  • Roma, Italy
  • Rozzano, Italy
  • Forli
    • Meldola, Forli, Italy
  • Frosinone
    • Sora, Frosinone, Italy
  • Lombardia
    • Lecco, Lombardia, Italy
• Poland
  • Krakow, Poland
  • Prabuty, Poland
  • Warszawa, Poland
  • Kujawsko-pomorskie
    • Torun, Kujawsko-pomorskie, Poland
  • Mazowieckie
    • Otwock, Mazowieckie, Poland
  • Pomorskie
    • Gdansk, Pomorskie, Poland
  • Zachodniopomorskie
    • Szczecin, Zachodniopomorskie, Poland
• Spain
  • Alicante, Spain
  • Barcelona, Spain
  • Barcelona (2), Spain
  • Barcelona (3), Spain
  • Barcelona (4), Spain
  • Barcelona (5), Spain
  • Barcelona (6), Spain
  • Burgos, Spain
  • Burgos (2), Spain
  • Madrid, Spain
  • Madrid (2), Spain
  • Madrid (3), Spain
  • Madrid (4), Spain
  • Manresa, Spain
  • Manresa (2), Spain
  • Palma de Mallorca, Spain
  • Valencia, Spain
  • Zaragoza, Spain
  • Zaragoza (2), Spain
  • A Coruña
    • La Coruna, A Coruña, Spain
  • Andalucia
    • Sevilla, Andalucia, Spain
  • Valenciana, Comunidad
    • Valencia, Valenciana, Comunidad, Spain
• United Kingdom
  • London, United Kingdom
  • London (2), United Kingdom
  • London (3), United Kingdom
  • Northwood, United Kingdom
  • Rickmansworth, United Kingdom
  • Southampton, United Kingdom
  • Wirral, United Kingdom
  • Hertfordshire
    • Stevenage, Hertfordshire, United Kingdom
• United States
  • Arizona
    • Glendale, Arizona, United States
  • California
    • Duarte, California, United States
    • La Verne, California, United States
    • Los Angeles, California, United States, 43210
    • San Francisco, California, United States
  • Florida
    • Port Saint Lucie, Florida, United States
    • Tampa, Florida, United States
  • Illinois
    • Chicago, Illinois, United States
    • Maywood, Illinois, United States
  • Indiana
    • Goshen, Indiana, United States, 46526
  • Kentucky
    • Louisville, Kentucky, United States
  • Michigan
    • Grand Rapids, Michigan, United States
  • Minnesota
    • Saint Cloud, Minnesota, United States
  • Missouri
    • Saint Louis, Missouri, United States
  • Nevada
    • Las Vegas, Nevada, United States
  • Ohio
    • Columbus, Ohio, United States
  • Oregon
    • Bend, Oregon, United States
    • Portland, Oregon, United States
    • Redmond, Oregon, United States, 97756
  • Tennessee
    • Chattanooga, Tennessee, United States
    • Knoxville, Tennessee, United States
    • Nashville, Tennessee, United States
  • Texas
    • Dallas, Texas, United States
  • Utah
    • Salt Lake City, Utah, United States
  • Virginia
    • Arlington, Virginia, United States
  • Washington
    • Seattle, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Must be greater or equal to 20 years of age

2. Must have cytologically or histologically confirmed NSCLC with either:

   • Metastatic disease (Stage IV) OR
   • Stage IIIB disease not amenable to surgery or curative intent.

   Note: It is permissible to use either AJCC Version 6.0 or the AJCC Version 7.0 staging system. For sites that use AJCC Version 7.0, T4M0 patients with other ipsilateral nodules and N0-N2 are still eligible.

3. If tumor histology is adenocarcinoma, must have wild-type EGFR genotype as assessed by a validated assay that includes exon 19 deletion and exon 21 (L858R) substitution.
4. Must have received one or two prior lines of systemic chemotherapy for advanced or metastatic disease, one of which must be a platinum-doublet therapy.
5. Must have disease progression or recurrence documented by radiographic assessment following treatment after last chemotherapy or chemoradiation regimen (completed within the previous 12 months).
6. Must have available recent (before treatment start) or archival tumor specimen.
7. Must have measurable disease for Part A, measurable disease or non-measurable disease for Part B
8. Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
9. Must have adequate hematological function
10. Must have adequate renal function
11. Must have adequate hepatic function
12. Agreement to use effective contraception while on treatment and for at least 6 months after end of treatment
13. Must have provided informed consent for study participation.

Exclusion Criteria:

1. Lung adenocarcinoma with an Anaplastic Lymphoma Kinase (ALK) gene rearrangement
2. Left ventricular ejection fraction (LVEF) less than 45%
3. Prior EGFR-targeted regimen, anti-HER2, anti-HER3, or anti-HER4 therapy
4. History of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated with no evidence of disease for greater or equal to 5 years
5. History of corneal disease
6. History of interstitial lung disease (ILD)
7. Clinically active brain metastases
8. Uncontrolled hypertension
9. Clinically significant ECG changes
10. Clinically significant (in the opinion of the Investigator) ascites or pleural effusion requiring chronic medical intervention
11. Myocardial infarction within 1 year before enrollment, symptomatic congestive heart failure, unstable angina, or unstable cardiac arrhythmia requiring medication
12. Treatment with anticancer therapy, antibody-based therapy, retinoid therapy, or hormonal therapy within 4 weeks before study drug treatment
13. Therapeutic radiation therapy or major surgery within 4 weeks before study drug treatment; or palliative radiation within 2 weeks before study drug treatment
14. Participation in clinical drug trials within 4 weeks
15. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.
16. History of hypersensitivity to any of the study drugs or to any excipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Placebo + erlotinib; Placebo infusion every 3 weeks and oral erlotinib 150 mg/day	Drug: Erlotinib; Oral erlotinib 150 mg/day; Drug: Placebo; Placebo infusion every 3 weeks; Other Names: Matching Placebo
EXPERIMENTAL: Patritumab + erlotinib; Infusion of Patritumab (loading dose of 18 mg/kg, followed by 9 mg/kg every 3 weeks) and oral erlotinib 150 mg/day	Drug: Erlotinib; Oral erlotinib 150 mg/day; Drug: Patritumab; Infusion of Patritumab (loading dose of 18 mg/kg, followed by 9 mg/kg every 3 weeks); Other Names: U3-1287

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Progression Free Survival (PFS) in Heregulin-high Participants	PFS is defined as the time from the date of randomization to the earlier of the dates of first objective documentation of radiographic disease progression (as per RECIST Version 1.1 per investigator assessment) or death resulting from any cause. Kaplan-Meier Estimate. Confidence interval (CI) for median was computed using the Brookmeyer-Crowley method. 80% confidence interval is included in the data table.	by trial termination (at 20 months)
Part A: Progression Free Survival (PFS) in Heregulin-low Participants	PFS is defined as the time from the date of randomization to the earlier of the dates of first objective documentation of radiographic disease progression (as per RECIST Version 1.1 per investigator assessment) or death resulting from any cause. Kaplan-Meier Estimate. Confidence interval (CI) for median was computed using the Brookmeyer-Crowley method. 80% confidence interval is included in the data table.	by trial termination (at 20 months)
Part B: Overall Survival	Percentage of participants still alive at the end of Part B	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Overall Survival in HRG High Participants	Key secondary efficacy endpoint: Percentage of participants who survived for the length of the trial	by trial termination (at 20 months)
Part A: Key Secondary Efficacy Endpoint: Overall Survival in HRG Low Participants	Key secondary efficacy endpoint: Percentage of participants who survived for the length of the trial	by trial termination (at 20 months)
Part B: Key Secondary Efficacy Endpoint: PFS, TTD	PFS is defined as the time from the date of randomization to the earlier of the dates of first objective documentation of radiographic disease progression (TTD, as per RECIST Version 1.1 per investigator assessment) or death resulting from any cause.	4 years
Part A: Objective Response Rate (ORR) in HRG High Participants	Key secondary efficacy endpoint: Objective response is defined as percentage of participants achieving complete response (CR) or partial response (PR) Denominator for percentages is the number of subjects with measurable disease in the full analysis set. The best overall response is the best response [in the order of CR, PR, stable disease (SD), and progressive disease (PD)] among all overall responses recorded from the start of treatment until the subject withdraws from the study. If there is no post-baseline tumor assessment or all post-baseline tumor assessments with overall response being Inevaluable captured in the CRF, the best overall response is classified as Inevaluable.	by trial termination (at 20 months)
Part A: Objective Response Rate (ORR) in HRG Low Participants	Key secondary efficacy endpoint: Objective response is defined as percentage of participants achieving complete response or partial response Denominator for percentages is the number of subjects with measurable disease in the full analysis set. The best overall response is the best response (in the order of CR, PR, SD, and PD) among all overall responses recorded from the start of treatment until the subject withdraws from the study. If there is no post-baseline tumor assessment or all post-baseline tumor assessments with overall response being Inevaluable captured in the CRF, the best overall response is classified as Inevaluable.	by trial termination (at 20 months)

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (ACTUAL): November 11, 2016
• Study Completion (ACTUAL): November 11, 2016

Study Registration Dates

• First Submitted: April 8, 2014
• First Submitted That Met QC Criteria: May 6, 2014
• First Posted (ESTIMATE): May 8, 2014

Study Record Updates

• Last Update Posted (ACTUAL): January 23, 2018
• Last Update Submitted That Met QC Criteria: December 22, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Respiratory Tract Diseases; Carcinoma; Neoplasms; Erlotinib; Lung Diseases; Thoracic Neoplasms; Pharmacologic Actions; Non-Small-Cell Lung; Therapeutic Uses; Bronchial Neoplasms; Neoplasms by Site; Molecular Mechanisms of Pharmacological Action; Lung Neoplasms; Respiratory Tract Neoplasms; Bronchogenic
• 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: U31287-A-U301; 2013-004371-12 (EUDRACT_NUMBER)