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

NCT02134015 | Terminated Phase 3 Results DMC

• 2 other identifiers: U31287-A-U3012013-004371-12
• Study Type: interventional
• Target: 145
• Locations: 10 countries
• Sites: 98

Brief Summary

1. 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. 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.

Conditions

Lung Cancer; Non-small Cell Lung Cancer

Keywords

Carcinoma; Non-Small-Cell Lung; Lung Neoplasms; Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Erlotinib; Therapeutic Uses; Pharmacologic Actions; Molecular Mechanisms of Pharmacological Action

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• Part A: Overall Survival in HRG High Participants

  by trial termination (at 20 months)

• Part A: Key Secondary Efficacy Endpoint: Overall Survival in HRG Low Participants

  by trial termination (at 20 months)

• Part B: Key Secondary Efficacy Endpoint: PFS, TTD

  4 years

• Part A: Objective Response Rate (ORR) in HRG High Participants

  by trial termination (at 20 months)

• Part A: Objective Response Rate (ORR) in HRG Low Participants

  by trial termination (at 20 months)

Study Arms (2)

Placebo + erlotinib

EXPERIMENTAL

Placebo infusion every 3 weeks and oral erlotinib 150 mg/day

Drug: Erlotinib; Drug: Placebo

Patritumab + erlotinib

EXPERIMENTAL

Infusion of Patritumab (loading dose of 18 mg/kg, followed by 9 mg/kg every 3 weeks) and oral erlotinib 150 mg/day

Drug: Patritumab; Drug: Erlotinib

Interventions

Patritumab DRUG

Infusion of Patritumab (loading dose of 18 mg/kg, followed by 9 mg/kg every 3 weeks)

Also known as: U3-1287

Patritumab + erlotinib

Erlotinib DRUG

Oral erlotinib 150 mg/day

Patritumab + erlotinib; Placebo + erlotinib

Placebo DRUG

Placebo infusion every 3 weeks

Also known as: Matching Placebo

Placebo + erlotinib

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be greater or equal to 20 years of age
• 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.
• 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.
• 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.
• Must have disease progression or recurrence documented by radiographic assessment following treatment after last chemotherapy or chemoradiation regimen (completed within the previous 12 months).
• Must have available recent (before treatment start) or archival tumor specimen.
• Must have measurable disease for Part A, measurable disease or non-measurable disease for Part B
• Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Must have adequate hematological function
• Must have adequate renal function
• Must have adequate hepatic function
• Agreement to use effective contraception while on treatment and for at least 6 months after end of treatment

You may not qualify if:

• Lung adenocarcinoma with an Anaplastic Lymphoma Kinase (ALK) gene rearrangement
• Left ventricular ejection fraction (LVEF) less than 45%
• Prior EGFR-targeted regimen, anti-HER2, anti-HER3, or anti-HER4 therapy
• 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
• History of corneal disease
• History of interstitial lung disease (ILD)
• Clinically active brain metastases
• Uncontrolled hypertension
• Clinically significant ECG changes
• Clinically significant (in the opinion of the Investigator) ascites or pleural effusion requiring chronic medical intervention
• Myocardial infarction within 1 year before enrollment, symptomatic congestive heart failure, unstable angina, or unstable cardiac arrhythmia requiring medication
• Treatment with anticancer therapy, antibody-based therapy, retinoid therapy, or hormonal therapy within 4 weeks before study drug treatment
• Therapeutic radiation therapy or major surgery within 4 weeks before study drug treatment; or palliative radiation within 2 weeks before study drug treatment
• Participation in clinical drug trials within 4 weeks
• Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.

Sponsors & Collaborators

• Daiichi Sankyo: lead
• Parexel: collaborator

Study Sites (98)

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Glendale, Arizona, United States

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Duarte, California, United States

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La Verne, California, United States

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Los Angeles, California, 43210, United States

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San Francisco, California, United States

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Port Saint Lucie, Florida, United States

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Tampa, Florida, United States

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Chicago, Illinois, United States

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Maywood, Illinois, United States

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Goshen, Indiana, 46526, United States

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Louisville, Kentucky, United States

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Grand Rapids, Michigan, United States

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Saint Cloud, Minnesota, United States

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St Louis, Missouri, United States

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Las Vegas, Nevada, United States

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Columbus, Ohio, United States

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Bend, Oregon, United States

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Portland, Oregon, United States

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Redmond, Oregon, 97756, United States

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Chattanooga, Tennessee, United States

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Knoxville, Tennessee, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Salt Lake City, Utah, United States

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Arlington, Virginia, United States

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Seattle, Washington, United States

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Brasschaat, Antwerpen, Belgium

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Brussels, Brussels Capital, Belgium

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Charleroi, Hainaut, Belgium

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Charleroi, Belgium

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Ghent, 9000, Belgium

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Liège, Belgium

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Yvoir, 5530, Belgium

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Hamilton, Ontario, Canada

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Kingston, Ontario, Canada

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Toronto, Ontario, Canada

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Lévis, Quebec, Canada

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Montreal, Quebec, Canada

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Ostava-Poruba, Czechia

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Ostrava-Poruba, Czechia

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Esslingen am Neckar, Baden-Wurttemberg, Germany

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Gerlingen, Baden-Wurttemberg, Germany

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Heidelberg, Baden-Wurttemberg, Germany

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Ulm, Baden-Wurttemberg, Germany

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Villingen-Schwenningen, Baden-Wurttemberg, Germany

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Gauting, Bavaria, 82131, Germany

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Munich, Bavaria, Germany

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Frankfurt am Main, Hesse, Germany

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Immenhausen, Hesse, Germany

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Cologne, North Rhine-Westphalia, Germany

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Rheine, North Rhine-Westphalia, Germany

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Mainz, Rhineland-Palatinate, Germany

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Halle, Saxony-Anhalt, Germany

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Großhansdorf, Schleswig-Holstein, Germany

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Giessen, Germany

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Székesfehérvár, Fejér, Hungary

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Győr, Győr-Moson-Sopron, Hungary

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Szolnok, Jász-Nagykun-Szolnok, Hungary

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Tatabánya, Hungary

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Meldola, Forli, Italy

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Sora, Frosinone, Italy

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Lecco, Lombardy, Italy

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Benevento, Italy

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Bologna, Italy

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Cremona, Italy

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Faenza, Italy

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Genova, Italy

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Milan, Italy

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Napoli, Italy

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Perugia, Italy

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Ravenna, Italy

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Rimini, Italy

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Roma, Italy

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Rozzano, Italy

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Torun, Kuyavian-Pomeranian Voivodeship, Poland

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Otwock, Masovian Voivodeship, Poland

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Gdansk, Pomeranian Voivodeship, Poland

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Szczecin, West Pomeranian Voivodeship, Poland

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Krakow, Poland

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Prabuty, Poland

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Warsaw, Poland

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A Coruña, A Coruña, Spain

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Seville, Andalusia, Spain

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Valencia, Valenciana, Comunidad, Spain

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Alicante, Spain

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Barcelona, Spain

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Burgos, Spain

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Madrid, Spain

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Manresa, Spain

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Palma de Mallorca, Spain

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Valencia, Spain

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Zaragoza, Spain

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Stevenage, Hertfordshire, United Kingdom

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London, United Kingdom

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Metropolitan Borough of Wirral, United Kingdom

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Northwood, United Kingdom

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Rickmansworth, United Kingdom

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Southampton, United Kingdom

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MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Interventions

patritumab; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Bronchial Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Global Clinical Leader
• Organization: Daiichi Sankyo, Inc.

DataSharing@dsi.com

9089926400

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2014
• First Posted: May 8, 2014
• Study Start: March 1, 2014
• Primary Completion: November 11, 2016
• Study Completion: November 11, 2016
• Last Updated: January 23, 2018
• Results First Posted: January 23, 2018

Record last verified: 2017-12

Locations

CA (5); US (26); GB (6); DE (15); HU (4); BE (7); CZ (2); IT (15); PL (7); ES (11)