A Study of LY2875358 in Participants With Non-Small Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations

Study Overview
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Brief Summary
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The primary purpose of this study is to compare the efficacy of the study drug LY2875358, given together with erlotinib, against erlotinib, alone. Participants will have Non-Small Cell Lung Cancer (NSCLC) that has advanced to Stage IV. Participants should not have been treated with drugs for Stage IV NSCLC, previously. All participants will get erlotinib alone, for approximately 8 weeks. Participants with radiographic disease control at the end of the erlotinib lead-in study period will be randomly assigned to receive LY2875358 plus erlotinib or erlotinib alone. Participants, who were chosen to receive erlotinib, alone, may cross over to the combination treatment at the time of progression.

Official Title
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A Randomized, Controlled Phase 2 Study Evaluating LY2875358 Plus Erlotinib Versus Erlotinib as First-Line Treatment in Metastatic Non-Small Cell Lung Cancer Patients With Activating EGFR Mutations Who Have Disease Control After an 8-Week Lead-In Treatment With Erlotinib

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Biological: LY2875358
* Drug: Erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed diagnosis of metastatic Stage IV NSCLC Have at least 1 measurable lesion whose presence is assessable using standard techniques by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) Have molecular evidence of an epidermal growth factor receptor mutation (EGFRmt) known to be associated with EGFR tyrosine kinase inhibitor (TKI) drug sensitivity (G719X, exon 19 deletion, L858R, L861Q) Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 Haven't received any prior systemic chemotherapy for Stage IV NSCLC (unless received as neoadjuvant or adjuvant therapy for early-stage NSCLC disease and completed therapy at least 6 months prior to enrollment) Availability of adequate tumor material (block or slides) Exclusion Criteria: Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or non-approved use of a drug or device Have previously completed or withdrawn from this study or any other study investigating LY2875358 Have a serious concomitant systemic disorder or significant cardiac disease Have interstitial pneumonia or interstitial fibrosis of the lung or have pleural effusion, pericardial fluids or ascites, requiring drainage every other week or more frequently Have a history of another malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to the study Have major surgery less than 2 weeks prior to the initiation of study treatment therapy Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2875358 plus Erlotinib<br>Lead In: Approximately 8 weeks of erlotinib 150 milligram (mg) given orally per day. Randomization: Erlotinib 150 mg given orally per day plus 750 mg LY2875358 given as 1.5 hours intravenous (IV) infusions on Days 1 and 15 of 28-day cycles. | Biological: LY2875358<br>* Administered IV<br>Drug: Erlotinib<br>* Administered Orally<br>|
| Active Comparator: Erlotinib<br>Lead In: Approximately 8 weeks of erlotinib 150 mg given orally per day. Randomization: Continue Erlotinib 150 mg given orally per day, in 28-day cycles. | Drug: Erlotinib<br>* Administered Orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) |  | Randomization to Objective Disease Progression or Death Due to Any Cause (Estimated 3 Years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Tumor Size (CTS) |  | Baseline to Measurement with Smallest Tumor Size (Estimated 3 Years) | 
| Proportion of Participants Exhibiting a Confirmed Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) |  | Baseline to Objective Disease Progression or Start of New Anticancer Therapy (Estimated 3 Years) | 
| Duration of Response (DoR) |  | Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Estimated 3 Years) | 
| Time to Progressive Disease (TTPD) |  | Randomization to Objective Disease Progression (Estimated 3 Years) | 
| Proportion of Participants Exhibiting a Stable Disease (SD) or a confirmed CR or PR (Disease Control Rate [DCR]) |  | Baseline to Objective Disease Progression or Participant Stops Study (Estimated 3 Years) | 
| Overall Survival (OS) |  | Randomization to Death Due to Any Cause (Estimated 5 Years) | 
| Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ) C30 (QLQ-C30) and Lung Cancer 13 (QLQ-LC13) |  | Baseline, Objective Disease Progression or Participants Stops Study (Estimated 3 Years) | 
| Pharmacokinetics (PK): Area Under the Concentration Time Curve During a Dosing Interval (AUCtau) of LY2875358 and Erlotinib |  | Baseline through Cycle 4 (28 Day Cycle) | 
| Proportion of Participants with Anti-LY2875358 Antibody Response |  | Baseline through 30 Day Follow Up (Estimated 3 Years) |