A Study for Participants With Pancreatic Cancer

The recommended Phase 2 dose for LY2603618 when administered approximately 24 hours after gemcitabine was based on the maximum tolerated dose and achievement of predefined LY2603618 plasma systemic exposures targets (area under the LY2603618 plasma concentration versus time curve from time zero to infinity [AUC(0-inf)] >21,000 nanogram*hour/milliliter [ng*h/mL] and maximum LY2603618 plasma concentration [Cmax] >2000 nanograms/milliliter [ng/mL]).

Overall survival (OS) time is defined as the time from the date of randomization to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS time was censored at the last contact date the participant was known to be alive prior to the cut-off date. OS was summarized using Kaplan-Meier estimates.

Plasma samples for pharmacokinetic (PK) analysis were collected following IV infusion of each study drug. However, the dose-normalized PK analysis of gemcitabine and dFdU were not reported because the gemcitabine and dFdU plasma concentration data generated for all participants with PK samples collected in this study were withdrawn (invalidated) as a result of the failure of the Incurred Sample Reanalysis (ISR) for both gemcitabine and dFdU. Therefore, only the LY2603618 plasma Cmax values are reported for each LY2603618 dose level on Cycle (C) 1 /Day (D) 1, Cycle 1 /Day 16, and Cycle 2 /Day 2. The number of PK observations (n) used in the analysis is presented for each dose level and time point.

Plasma samples for PK analysis were collected following IV infusion of each study drug. However, the dose-normalized PK analysis of gemcitabine and dFdU were not reported because the gemcitabine and dFdU plasma concentration data generated for all participants with PK samples collected in this study were withdrawn (invalidated) as a result of the failure of the Incurred Sample Reanalysis (ISR) for both gemcitabine and dFdU. Therefore, only the LY2603618 plasma Cmax values are reported at the 230 mg LY2603618 dose level on Cycle 1 /Day 1, Cycle 1 /Day 16, and Cycle 2 /Day 2. The number of PK observations (n) used in the analysis is presented for each time point.

Plasma samples for PK analysis were collected following IV infusion of each study drug. However, the dose-normalized PK analysis of gemcitabine and dFdU were not reported because the gemcitabine plasma and dFdU concentration data generated for all participants with PK samples collected in this study were withdrawn (invalidated) as a result of the failure of the Incurred Sample Reanalysis (ISR) for both gemcitabine and dFdU. Therefore, only LY2603618 plasma AUC from time zero to 24 hours (AUC[0-24]), AUC from time zero to the last time point with a measurable concentration (AUC[0-tlast]), and AUC from time zero to infinity (AUC[0-inf]) values are reported for each LY2603618 dose level on Cycle 1 /Day 1, Cycle 1 /Day 16, and Cycle 2 /Day 2. The number of PK observations (n) used in the analysis is presented for each dose level and time point.

Plasma samples for PK analysis were collected following IV infusion of each study drug. However, the dose-normalized PK analysis of gemcitabine and dFdU were not reported because the gemcitabine and dFdU plasma concentration data generated for all participants with PK samples collected in this study were withdrawn (invalidated) as a result of the failure of the Incurred Sample Reanalysis (ISR) for both gemcitabine and dFdU. Therefore, only the LY2603618 plasma AUC(0-24), AUC(0-tlast), and AUC(0-inf) values are reported for the 230 mg LY2603618 dose on Cycle 1 /Day 1, Cycle 1 /Day 16, and Cycle 2 /Day 2. The number of PK observations (n) used in the analysis is presented for each time point.

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.

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) guidelines. 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.

Clinical benefit rate is the best response CR, PR, or stable disease (SD) as classified by the investigators according to the RECIST v1.1 guidelines. 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. Overall response 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.

Duration of response was defined as the time from the first observation of complete response (CR) or partial response (PR) to the first observation of progressive disease or death from any cause. For participants who were not known to have died as of the data-inclusion cut-off date and who do not have progressive disease, the duration was censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent anticancer therapy (systemic, radiologic, or surgery). Participants were also censored at the last valid assessment prior to missing more than 1 consecutive scheduled assessment. Duration of response was summarized using Kaplan-Meier estimates.

The QT interval is a measure of the time between the start of the Q wave and the end of the T wave. Twelve-lead electrocardiogram (ECG) data was used to calculate the corrected QT (QTc) based on Fridericia's formula (QTc=QT/RR^0.33, where RR is the interval between two R waves). For each participant, changes in QTc were calculated by subtracting the reading taken before LY2603618 administration from the reading taken after LY2603618 administration on Days 2 and 16 during Cycle 1. The number of participants in which the change in QTc was <=30 milliseconds (msec), >30-60 msec, or >60 msec is presented by dose group and overall.

The QT interval is a measure of the time between the start of the Q wave and the end of the T wave. Twelve-lead ECG data was used to calculate QTc based on Fridericia's formula (QTc=QT/RR^0.33, where RR is the interval between two R waves). For each participant, changes in QTc were calculated by subtracting the reading taken before LY2603618 administration from the reading taken after LY2603618 administration on Days 2 and 16 during Cycle 1. The number of participants in which the change in QTc was <=30 milliseconds (msec), >30-60 msec, or >60 msec is presented.

The number of participants who died during the post-study period of Phase 1 does not include the outcomes for the 4 participants who died while on treatment during Phase 2 as captured in the Participant Flow Table. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.