A Study of Prexasertib (LY2606368) in Participants With Extensive Stage Disease Small Cell Lung Cancer

ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions

Time frame: Baseline to 10 months

Population: All randomized participants who received at least 1 dose of study drug.

LCSS is a 9-item questionnaire, six measuring major symptoms for lung malignancies (appetite, fatigue, cough, dyspnea, hemoptysis and pain), and 3 summation items related to total symptomatic distress, activity status and overall quality of life. Participant responses were measured using visual analogue scales (VAS) with 100-mm lines. The LCSS total score was defined as the mean of the 9 items of the scale, each scored between 0 (for best outcome) to 100 (for worst outcome).

Time frame: Baseline up to 9 months

Population: All participants in Cohort 1 and Cohort 2. Cohort 3 was added by protocol addendum and data were not collected with non missing baseline and post baseline scores.

ABSI was the mean score for the six major lung cancer symptoms (appetite, fatigue, cough, dyspnea, hemoptysis and pain), each scored between 0 (for best outcome) to 100 (for worst outcome).

Time frame: Baseline up to 9 months

Population: All participants in Cohort 1 and Cohort 2. Cohort 3 was added by protocol addendum and data were not collected with non missing baseline and post baseline scores.

Disease control rate (DCR) is defined as the percentage of participants achieving a best overall response of CR, PR, or SD as determined by RECIST 1.1. CR is defined as a disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \<10 mm and normalization of tumor marker results; PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters; SD is defined as neither sufficient shrinking to qualify as PR nor sufficient increase to qualify for PD.

Time frame: Baseline through Disease Progression or Death from Any Cause to 28 months

Population: All randomized participants who received at least 1 dose of study drug.

DoR the time from the date of an objective response until Progressive Disease (PD): was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Time frame: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause up to 9 months

Population: Analysis was not performed due to only 3 responders in Cohort 1, no in Cohort 2 or 3. Individual data for Cohort 1 is presented.

OS defined as from randomization date to the date of death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive.

Time frame: Baseline up to 28 months

Population: All randomized participants. 8 participants were censored from Cohort 1, 5 participants were censored from Cohort 2 and 4 participants censored from Cohort 3.

Pharmacokinetics: Area Under the Concentration Curve of Prexasertib

Time frame: Cycle 1,3, 5, and 7: Day 1, Day 2 and Day 3- Prior to start of infusion, end of infusion plus 10 minutes, Day 8: anytime

Population: All participants in Part A1 that received at least 1 dose of study drug and had evaluable PK data.

Pharmacokinetics(PK): Maximum Concentration of Prexasertib. The same dose was administered to Cohort 1 and Cohort 2 and were combined for analysis.

Time frame: Cycle 1,3, 5, and 7: Day 1, Day 2 and Day 3- Prior to start of infusion, end of infusion plus 10 minutes, Day 8: anytime

Population: All randomized participants who received at least 1 dose of study drug and had evaluable PK parameters. Cohort 1 and Cohort 2 received the same dose and were combined per protocol.

Pharmacokinetics(PK): Maximum Concentration of Prexasertib

Time frame: Cycle 1,3, 5, and 7: Day 1, Day 2 and Day 3- Prior to start of infusion, end of infusion plus 10 minutes, Day 8: anytime

Population: Al randomized participants with at least 1 dose of study drug, received 40 mg/m\^2 and had evaluable PK parameters.

PFS defined as the from randomization date to the first evidence of disease progression as defined by RECIST v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of first dose, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.

Time frame: Baseline to Disease Progression or Death (up to 9 months)

Population: All randomized participants. 4 participants were censored from Prexasertib Cohort 1 and 1 participant from Prexasertib Cohort 3.