A Study of Emibetuzumab in Non Small Cell Lung Cancer (NSCLC) Participants

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the efficacy of the study drug known as LY2875358, administered alone or in combination with a second drug named Erlotinib, in participants affected by a defined type of lung cancer (MET biomarker diagnostic positive Non-Small-Cell Lung Cancer) that experienced a disease progression during the most recent treatment with Erlotinib.

Official Title
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A Randomized, Open-Label Phase 2 Study Evaluating LY2875358 Plus Erlotinib and LY2875358 Monotherapy in MET Diagnostic Positive NSCLC Patients With Acquired Resistance to Erlotinib

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: Emibetuzumab
* Drug: Erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of metastatic Stage IV NSCLC At least 1 measurable extra-central nervous system (CNS) lesion Documented radiographic progression while on continuous treatment with erlotinib monotherapy Objective clinical benefit from erlotinib treatment as defined by either documented partial or complete response or stable disease ≥6 months or, if most recent erlotinib treatment has been initiated based on documented epidermal growth factor receptor mutation (EGFRmt) status, at least 12 weeks stable disease Determined to be MET diagnostic positive (+) Availability of a tumor sample post-erlotinib progression Eastern Cooperative Oncology Group (ECOG) performance status ≤2 Have adequate organ function 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 been treated with LY2875358 or any other MET-targeting experimental therapeutic 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 initiation of study treatment therapy Pregnant or lactating women Have symptomatic CNS metastasis

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: Arm A: Emibetuzumab plus Erlotinib<br>750 milligram (mg) Emibetuzumab flat dose given as a 1.5 hour intravenous (IV) infusion on Days 1 and 15 of a 28-day cycle and Erlotinib 150 mg given orally once daily on a 28-day cycle. | Drug: Emibetuzumab<br>* Administered IV<br>* Other names: LY2875358;Drug: Erlotinib<br>* Administered Orally<br>|
| Experimental: Arm B: Emibetuzumab<br>750 mg Emibetuzumab flat dose given as a 1.5-hour IV infusion on Days 1 and 15 of a 28-day cycle. | Drug: Emibetuzumab<br>* Administered IV<br>* Other names: LY2875358;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) | ORR is confirmed best overall tumor response of CR or PR. According to RECIST v1.1, CR was defined as the disappearance of all target and non-target lesions; PR defined as a >30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD. Percentage of participants was calculated as: (total number of participants with CR or PR from start of the treatment until disease progression or recurrence)/total number of participants treated) * 100. | Baseline to Objective Disease Progression or Start of New Anticancer Therapy (Up to 15 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS defined as date of randomization until the date of objectively determined progression defined by Response Evaluation Criteria in Solid Tumors criteria or death from any cause, whichever is first. Progressive disease (PD) defined as ≥20% increase in sum of diameter of target lesion with the sum demonstrating an increase of ≥5 mm; appearance of ≥1 new lesions or unequivocal progression of non- target lesions. Participants with no baseline disease assessment were censored at randomization date, regardless of whether or not objectively determined PD or death was observed; participants not known to have died or to have objective progression as of data inclusion cutoff were censored at last post baseline radiological assessment date or randomization date, if there was no post baseline radiological assessment. | Baseline to Objective Disease Progression or Death (Up to 24 Months) | 
| Time to Progressive Disease |  | Baseline to Objective Disease Progression (Up to 24 Months) | 
| Change in Tumor Size (CTS) | Zero participants analyzed. CTS data was not collected for analysis due to N=0 CR and N=3 PR. | Baseline to Measurement with Smallest Tumor Size (Up to 24 Months) | 
| Secondary: Percentage of Participants Who Achieved Best Overall Disease Response of CR, PR or Stable Disease (SD) [Disease Control Rate (DCR)] | Participants achieved disease control if they had a best overall response of PR, CR or SD. According to RECIST v1.1, CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to <10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels (if tumor markers were initially above the upper limit of normal [ULN]); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started. The percentage of participants who achieved disease control equals (number of participants with CR, PR, or SD)/(number of participants assessed)*100. | Baseline to Objective Disease Progression or Participant Stops Study (Up to 24 Months) | 
| Duration of Response (DoR) | Zero participants analyzed. Duration of Response for CR and PR data was not collected for analysis due to N=0 CR and N=3 PR. | Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 24 Months) | 
| Overall Survival (OS) | OS was defined as duration from the date of study enrollment to the date of death from any cause. Participants not known to have died as of the data inclusion cut-off date were censored at the date of last contact. The last contact for participants in post-discontinuation was the last date participant was known to be alive. | Baseline to Death Due to Any Cause (Up to 24 Months) | 
| Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires C30 (QLQ-C30) | EORTC QLQ-C30 v3.0 is a self-administered questionnaire with multidimensional scales that measures 5 functional domains (physical, role, cognitive, emotional, and social), global health status, and symptom scales of fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation and diarrhea, and financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms. | Baseline, Objective Disease Progression or Participants Stops Study (Up to 24 Months) | 
| Change From Baseline in EORTC Quality of Life Questionnaires Lung Cancer 13 (QLQ-LC13) | The EORTC lung module QLQ-LC13 comprises 13 items consisting of one multi-item scale to assess dyspnea and a series of single-item measures assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. The higher scores represent a greater degree of symptoms. | Baseline, Objective Disease Progression or Participants Stops Study (Up to 24 Months) | 
| Change From Baseline in EuroQol 5-Dimensional Scale (EQ-5D) | The EQ-5D is a generic, multidimensional, health status instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the United Kingdom (UK) population-based algorithm. The possible values for the Index Score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension). A negative change indicated a worsening of the participant's health status. Additionally, participants will indicate their current health status by marking on a continuum ranging from 100 (best imaginable health state) to 0 (worst imaginable health state). | Baseline, Objective Disease Progression or Participants Stops Study (Up to 24 Months) | 
| Pharmacokinetics (PK): Area Under the Concentration (AUC) of Emibetuzumab | AUC(0-tlast) = area under the concentration versus time curve from time zero through the last quantifiable sample. | Cycle1 Day 1 (C1 D1): Pre-dose and End of infusion; C1 D8: Pre-dose; C1 D15, C2 D1, C2 D15, C3 D1, C3 D15, C4 D1, C4 D15: Pre-dose and End of Infusion | 
| Number of Participants With Anti-Emibetuzumab Antibody (ADA) Response |  | Baseline through 30-Day Follow-Up (Up to 24 Months) |