Study of Patritumab in Combination With Erlotinib in Subjects With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC). (HER3-Lung)
Condition: Lung Cancer; Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Patritumab; Erlotinib; Placebo
Intervention description: Infusion of Patritumab (loading dose of 18 mg/kg, followed by 9 mg/kg every 3 weeks); Oral erlotinib 150 mg/day; Placebo infusion every 3 weeks
Intervention MeSH terms: Erlotinib Hydrochloride
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 145.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
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

Summary:

      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.
    

Eligibility criteria:

        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.