A Study of Advanced or Metastatic Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the efficacy and safety of LY2603618 in combination with pemetrexed and any side effects that might be associated with it along with determining the effects of LY2603618 in combination with pemetrexed in participants with advanced or metastatic Non-small Cell Lung Cancer (NSCLC).

Official Title
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A Phase 2 Study to Evaluate LY2603618 in Combination With Pemetrexed in Patients With Advanced or Metastatic Non-small Cell Lung Cancer

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: LY2603618
* Drug: Pemetrexed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must agree to have a tumor biopsy at screening Must have a diagnosis of advanced or metastatic non-squamous non-small cell lung cancer that has progressed after certain prior treatment Must be available for the duration of the study and willing to follow the study procedures If participant is a woman that is capable of having children, must have a negative pregnancy test within 7 days of taking first dose of study drug Must have discontinued radiation therapy at least 4 weeks before entering this study Exclusion Criteria: Must not have taken an unapproved drug as treatment for any indication within the last 28 days before starting study treatment. Must not be pregnant or lactating, are considering becoming pregnant, or are considering fathering a child. Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial until the participant's physician considers it safe to become pregnant or father a child. Must not have known positive test in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb). Must not have previously participated in a study involving LY2603618 Must not have previously taken pemetrexed for cancer Must not have a known allergy to LY2603618 or pemetrexed Must not currently have an infection that may affect participant's ability to tolerate the therapy Must not have a serious medical condition or disorder that would make it unsafe for you to participate in the study such as uncontrolled diabetes or chest pain due to heart disease If taking certain medications called non-steroidal anti-inflammatory drugs (NSAIDS), such as ibuprofen, must be able to stop taking these medications according to certain guidelines

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2603618 and Pemetrexed<br> | Drug: LY2603618<br>* 150 milligram per square meter (mg/m^2) intravenously on Day 2 of each 21 day cycle repeating every 21 days for a minimum of 2 cycles continuing until disease progression<br>Drug: Pemetrexed<br>* 500 mg/m^2 intravenously on Day 1 of each 21 Day cycle repeating every 21 days for a minimum of 2 cycles or until disease progression<br>* Other names: LY231514;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Tumor Response - Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)] | Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of not-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100. | Baseline until Progressive Disease or Study Discontinuation (Up to 23 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved a Best Response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Clinical Benefit Rate) | Clinical benefit rate is the best response CR, PR, or stable disease (SD) as classified by the investigators according to the RECIST v1.1. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of not-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameter since treatment started. Clinical benefit rate is calculated as a total number of participants with CR, PR, or SD divided by the total number of participants with at least 1 measurable lesion, multiplied by 100. | Baseline until Progressive Disease or Study Discontinuation (Up to 23 Months) | 
| Progression-free Survival (PFS) | Progression-free survival (PFS) time was defined as the time from the date of randomization to the first date of progressive disease (symptomatic or objective) or death due to any cause, whichever occurred first. For participants who were not known to have died or progressed as of the data-inclusion cutoff date, PFS time was censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systematic anticancer therapy. PFS was summarized using Kaplan-Meier estimates. | Baseline to Progressive Disease or Death Due to Any Cause (Up to 27.1 Months) | 
| Duration of Response | Duration of Response is defined as the time from the first observation of CR or PR to the first observation of progressive disease (PD) or death from any cause. A response is defined as a confirmed objective status of CR or PR. For participants who are not known to have died as of the data inclusion cut-off date and who do not have PD, the duration will be censored at the date of the last objective progression free disease assessment prior to the date of any subsequent anticancer therapy. | First Observation of CR or PR until Progressive Disease or Death Due to Any Cause (Up to 23 Months) | 
| Change in Symptom Burden Scores of Lung Cancer Symptom Scale (LCSS) | The LCSS participants scale is a 9-item questionnaire. Six questions are symptom-specific measures for lung cancer (appetite, fatigue, cough, dyspnea, hemoptysis and pain), and 3 summation items describe total symptomatic distress, activity status, and overall quality of life. Participant responses were measured using visual analogue scales (VAS) with 100-milliliter (mm) lines. Scores range from 0 (for best outcome) to 100 (for worst outcome). The Average Symptom Burden Index (ASBI) was calculated as the mean of 6 symptom-specific questions from the LCSS. | Baseline until End of Study (Up to 27.1 Months) | 
| Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY2603618 |  | Day 2 and Day 3 of Cycle 1 and Cycle 2: Prior to End of Infusion (EOI); EOI + 1-2 hr; EOI + 4-6 hr; EOI + 20-28 hr; anytime on Day 8 of Cycle 1 and Cycle 2 | 
| PK: Maximum Plasma Concentration (Cmax) of Pemetrexed |  | Day 1 and Day 2 of Cycle 1 and Cycle 2: Prior to End of Infusion (EOI); EOI + 1-2 hour (hr); EOI + 4-6- hr; EOI + 20-28 hr | 
| PK: Area Under the Plasma Concentration vs. Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2603618 |  | Day 2 and Day 3 of Cycle 1 and Cycle 2: Prior to End of Infusion (EOI); EOI + 1-2 hr; EOI + 4-6 hr; EOI + 20-28 hr; anytime on Day 8 of Cycle 1 and Cycle 2 | 
| PK: Area Under the Plasma Concentration vs. Time Curve From Time Zero to Infinity [AUC(0-∞)] of Pemetrexed |  | Day 1 and Day 2 of Cycle 1 and Cycle 2: Prior to End of Infusion (EOI); EOI + 1-2 hour (hr); EOI + 4-6- hr; EOI + 20-28 hr |