Study of LY2181308 in Combination With Docetaxel Versus Docetaxel in Patients With Non-Small Cell Lung Cancer

The tumor size was defined as the sum of the longest diameters for the target lesions. The sum of lesion diameters was calculated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. The log ratio of tumor size at the end of Cycle 2 to tumor size at baseline was calculated for each participant.

Time frame: Baseline, End of Cycle 2 (1 cycle = 21 days)

Population: Participants who received at least 1 dose of study drug and had tumor size measurements (according to the pre-specified inclusion criteria) at baseline and at the end of Cycle 2.

Duration of response was measured from the time measurement criteria were met for complete response (CR) or partial response (PR) (whichever was first recorded) until the first date of documented progressive disease (PD) or death. Complete response (CR) was defined as the disappearance of all target lesions; PR was defined as at least a 30% decrease in sum of longest diameter of target lesions; PD was defined as at least a 20% increase in sum of longest diameter of target lesions. Duration of response was censored at the date of the last assessment or follow-up visit for responders who were still alive and had not progressed.

Time frame: Time of response to progressive disease (PD) (approximately 8.7 months)

Population: Participants who received at least 1 dose of study drug and achieved CR or PR. A total of 0 participants were censored in the Docetaxel arm; 2 participants were censored in the LY2181308 + Docetaxel arm.

The worsening of symptoms was defined as a 15-millimeter (mm) increase in any 1 symptom on the Lung Cancer Symptom Scale (LCSS). The LCSS is an assessment used to evaluate 6 major symptoms associated with lung malignancies and their effect on 3 overall symptomatic items: distress, functional activities and global quality of life. LCSS consists of 2 scales: 1 completed by the participant and 1 completed by the health care professional (which is the average symptom burden index \[ASBI\]). Participant-reported outcomes are assessed using 9 visual analog scales (100-mm horizontal line). Participants indicate intensity of response to the items in question (0 = lowest rating, 100 = highest rating). The LCSS total score ranges from 0 (lowest rating) to 100 (highest rating) and was defined as the mean over all 9 items. ASBI was calculated as the mean of six symptom-specific questions from the LCSS, with scores range from 0 (for best outcome) to 100 (for worst outcome).

Time frame: Cycle 2 Day 1

Population: Participants who received at least 1 dose of study drug and had evaluable LCSS data.

The worsening of symptoms was defined as a 15-millimeter (mm) increase in any 1 symptom on the Lung Cancer Symptom Scale (LCSS). The LCSS is an assessment used to evaluate 6 major symptoms associated with lung malignancies and their effect on 3 overall symptomatic items: distress, functional activities and global quality of life. LCSS consists of 2 scales: 1 completed by the participant and 1 completed by the health care professional (which is the average symptom burden index \[ASBI\]). Participant-reported outcomes are assessed using 9 visual analog scales (100-mm horizontal line). Participants indicate intensity of response to the items in question (0 = lowest rating, 100 = highest rating). The LCSS total score ranges from 0 (lowest rating) to 100 (highest rating) and was defined as the mean over all 9 items.

Time frame: Cycle 2 Day 1

Population: Participants who received at least 1 dose of study drug and had evaluable LCSS data.

Safety analyses included listings and/or summaries of the following: 1. CTCAE for laboratory and non-laboratory parameters possibly related to study drug; 2. CTCAE Grades 3 and 4 for laboratory and non-laboratory parameters possibly related to study drug (Grade 3 - severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care. Grade 4 - life-threatening consequences; urgent intervention indicated); 3. Dose adjustments due to adverse events (AEs).

Time frame: Randomization through long-term follow up (up to 21.6 months)

Population: Participants who received at least 1 dose of study drug.

Overall survival (OS) was the duration from enrollment to death from any cause. For participants who were alive, OS is censored at the date of last contact.

Time frame: Randomization to date of death from any cause (up to 21.6 months)

Population: Participants who received at least 1 dose of study drug. A total of 20 participants were censored in the Docetaxel arm; 41 participants were censored in the LY2181308 + Docetaxel arm.

Complete response (CR) was defined as the disappearance of all target lesions; partial response (PR) was defined as at least a 30% decrease in sum of longest diameter of target lesions.

Time frame: Randomization to the first date of progressive disease (up to 12.1 months)

Population: Participants who received at least 1 dose of study drug. A total of 47 participants were censored in the Docetaxel arm; 107 participants were censored in the LY2181308 + Docetaxel arm.

Pharmacokinetics: Area Under the Concentration Curve From Zero to 4 hours (AUC\[0-4\]) for LY2181309 and Docetaxel

Time frame: Docetaxel: Cycle(C)1 Day(D)1:0,1,1.25,1.75,3,4 hours(h);LY2181308 + Docetaxel: C1 D-1:3,4 h;D1:0,3,4 h

Population: Participants who received at least 1 dose of study drug and who had an interpretable pharmacokinetic profile

Pharmacokinetics: Area Under the Drug Concentration-Time Curve From Zero to Infinity (AUC\[0 ∞\]) of LY2181309 and Docetaxel

Time frame: Docetaxel: Cycle(C)1 Day(D)1:0,1,1.25,1.75,3,4,5,505,513,2521 hours(h);LY2181308 + Docetaxel: C1 D -1:3,4 h;D1:0,3,4,5,5.25,5.75,7,8,120,504,507,509,1008,1512,1515,1517,2016, 2520,2523,2525 h

Population: Participants who received at least 1 dose of study drug and who had an interpretable pharmacokinetic profile

Progression Free Survival (PFS) was defined as the time from date of first dose to the first observation of disease progression or death due to any cause. PFS time was censored at the date of the last assessment visit for participants who were still alive and who did not have documented progressive disease as of the data cut-off date.

Time frame: Randomization to the first date of progressive disease or death from any cause (up to 12.88 months)

Population: Participants who received at least 1 dose of study drug. A total of 10 participants were censored in the Docetaxel arm; 18 participants were censored in the LY2181308 + Docetaxel arm.

Time to documented disease progression was defined as the time from the date of randomization to the first date of documented progression. Progressive disease (PD) was defined as at least a 20% increase in sum of longest diameter of target lesions. Time to documented disease progression was censored at the date of the last assessment visit for participants who had not had documented progressive disease as of the data cut-off date.

Time frame: Randomization to the first date of progressive disease (up to 12.9 months)

Population: Participants who received at least 1 dose of study drug. A total of 15 participants were censored in the Docetaxel arm; 38 participants were censored in the LY2181308 + Docetaxel arm.

Time to objective tumor response was defined as the time from the date of randomization to the first date of documented objective tumor response. Time to objective tumor response was censored at the date of the last assessment visit for participants who had not had documented response as of the data cut-off date. Complete response (CR) was defined as the disappearance of all target lesions; partial response (PR) was defined as at least a 30% decrease in sum of the longest diameter of target lesions.

Time frame: Randomization to the date of first response (up to 12.1 months)

Population: Participants who received at least 1 dose of study drug. A total of 47 participants were censored in the Docetaxel arm; 107 participants were censored in the LY2181308 + Docetaxel arm.

The worsening of symptoms was defined as a 15-millimeter (mm) increase in any 1 symptom on the LCSS. The LCSS is an assessment used to evaluate 6 major symptoms associated with lung malignancies and their effect on overall symptomatic distress, functional activities, and global quality of life. LCSS consists of 2 scales: 1 completed by the participant and 1 completed by the health care professional (which is the average symptom burden index \[ASBI\]). Participant-reported outcomes are assessed using 9 visual analog scales (100-mm horizontal line). Participants indicate intensity of response to the items in question (0 = lowest rating, 100 = highest rating). The LCSS total score ranges from 0 (lowest rating) to 100 (highest rating). The LCSS total score was defined as the mean over all 9 items. Time to worsening of symptoms was censored at the date of the last assessment visit for participants who did not experience any worsening of symptoms as of the data cut-off date.

Time frame: Baseline to the worsening of symptoms (up to 4.6 months)

Population: Participants who received at least 1 dose of study drug. A total of 10 participants were censored in the Docetaxel arm; 26 participants were censored in the LY2181308 + Docetaxel arm.