I4C-MC-JTBC

Eli Lilly and Company

Lilly Corporate Center, Indianapolis, IN, United States, 46285

Available Mon - Fri 9 AM - 5 PM EST , Eli Lilly and Company, 1 877-CTLilly,

Available Mon - Fri 9 AM - 5 PM EST , Eli Lilly and Company, 1 877-285-4559,

No

No

No

Final

24 Mar 2016

No

Yes

24 Mar 2016

No

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 [≥10% of cells with 2+ or 3+ MET expression determined by immunohistochemistry (IHC)] Non-Small-Cell Lung Cancer [NSCLC]) that experienced a disease progression during the most recent treatment with Erlotinib.

This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.

21 Aug 2013

Yes

No

Netherlands: 10

Spain: 10

United Kingdom: 9

Belgium: 9

France: 7

Germany: 5

Italy: 3

Israel: 11

Korea, Republic of: 6

United States: 41

111

53

0

0

0

0

0

0

60

50

1

Overall Study (overall period)

Not applicable

Not blinded. Randomized-uncontrolled allocation method.

Yes

Emibetuzumab

LY2875358

Solution for injection/infusion

Intravenous use

750 mg Emibetuzumab flat dose given as a 1.5 hour IV infusion on Days 1 and 15 of a 28-day cycle.

Erlotinib

Tablet

Oral use

Erlotinib 150 mg given orally once daily on a 28-day cycle.

Emibetuzumab

LY2875358

Solution for infusion

Intravenous use

750 mg Emibetuzumab flat dose given as a 1.5-hour IV infusion on Days 1 and 15 of a 28-day cycle.

Emibetuzumab + Erlotinib

Emibetuzumab 750mg

MET-High Analysis Population

Participants with MET-High expression status (i.e ≥60% of cells with 2+ or 3+ MET expression determined by IHC) based on their post-erlotinib progression NSCLC tumor sample.

MET-High Analysis Population (Emibetuzumab + Erlotinib)

Participants in the Emibetuzumab + Erlotinib treatment arm with MET-High expression status based on their post-erlotinib progression NSCLC tumor sample.

MET-High Analysis Population Emibetuzumab)

Participants in the Emibetuzumab treatment arm with MET-High expression status based on their post-erlotinib progression NSCLC tumor sample.

Population of Emibetuzumab

All participants who received Emibetuzumab on Cycle 1, Day 1, and contributed samples for analysis.

Emibetuzumab + Erlotinib

Emibetuzumab 750mg

MET-High Analysis Population

Participants with MET-High expression status (i.e ≥60% of cells with 2+ or 3+ MET expression determined by IHC) based on their post-erlotinib progression NSCLC tumor sample.

MET-High Analysis Population (Emibetuzumab + Erlotinib)

Participants in the Emibetuzumab + Erlotinib treatment arm with MET-High expression status based on their post-erlotinib progression NSCLC tumor sample.

MET-High Analysis Population Emibetuzumab)

Participants in the Emibetuzumab treatment arm with MET-High expression status based on their post-erlotinib progression NSCLC tumor sample.

Population of Emibetuzumab

All participants who received Emibetuzumab on Cycle 1, Day 1, and contributed samples for analysis.

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. Analysis population description: All participants who are MET diagnostic positive based on the results of their post-erlotinib progression tumor sample and resistance to erlotinib.

Primary

Baseline to Objective Disease Progression or Start of New Anticancer Therapy (up to 15 Months)

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. Analysis Population Description: All participants who are MET diagnostic positive based on results of their post-erlotinib progression tumor sample and resistance to erlotinib.

Secondary

Baseline to Objective Disease Progression or Death Due to Any Cause (Up to 24 Months).

Analysis Population Description: All participants who are MET diagnostic positive based on the results of their post-erlotinib progression tumor sample and resistance to erlotinib.

Secondary

Baseline to Objective Disease Progression (up to 24 Months)

Zero participants were analyzed. The number of participants with tumor reduction was not large enough for a meaningful analysis.

Secondary

Baseline to Measurement with Smallest Tumor Size (Up to 24 Months)

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.

Secondary

Baseline to Objective Disease Progression or Participant Stops Study ( 24 Months) Population description: All participants who are MET diagnostic positive based on results of their post-erlotinib progression tumor sample and resistance to erlotinib.

Zero participants were analyzed. The number of all responders (participants with CR or PR) was too small for a meaningful analysis, as there were only 4 responders.

Secondary

Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (up to 24 Months)

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. Analysis Population Description: All participants who are MET diagnostic positive based on the results of their post-erlotinib progression tumor sample and resistance to erlotinib.

Secondary

Baseline to Death Due to Any Cause (up to 28 Months)

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. Analysis Population Description: All randomized participants with EORTC QLQ-C30 values at baseline.

Secondary

Baseline, Objective Disease Progression or Participants Stops Study (up to 24 Months)

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. Analysis Population Description: All randomized participants with EORTC QLQ-LC13 values at baseline.

Secondary

Baseline, Objective Disease Progression or Participants Stops Study (up to 24 Months)

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, patients will indicate their current health status by marking on a continuum ranging from 100 (best imaginable health state) to 0 (worst imaginable health state). Analysis Population Description: All randomized participants with EQ-5D values at baseline.

Secondary

Baseline, Objective Disease Progression or Participants Stops Study (Up to 24 Months)

AUC(0-tlast) = area under the concentration versus time curve from time zero through the last quantifiable sample. Analysis Population Description: All participants who received Emibetuzumab on Cycle 1, Day 1, and contributed samples for analysis.

Secondary

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

Analysis Population Description: All participants who received at least one dose of study drug and have sufficient Anti-Emibetuzumab Antibody sample for the analysis.

Secondary

Baseline through 30-Day Follow-Up (Up to 24 Months)

Entire Study

I4C-MC-JTBC

18.1

Emibetuzumab 750mg + ERLOTINIB 150mg

Emibetuzumab 750mg