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

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.