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

Study Overview
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Brief Summary
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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. 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.

Official Title
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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

Conditions
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Lung Cancer, Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Patritumab
* Drug: Erlotinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Must have provided informed consent for study participation. Exclusion Criteria: 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. History of hypersensitivity to any of the study drugs or to any excipients.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bronchial Neoplasms, Thoracic Neoplasms, Molecular Mechanisms of Pharmacological Action, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Bronchogenic, Respiratory Tract Neoplasms, Neoplasms by Site, Neoplasms, Lung Diseases, Respiratory Tract Diseases, Erlotinib, Therapeutic Uses, Pharmacologic Actions