A Study of LY3039478 in Participants With Advanced Cancer

DLT was defined as an adverse event (AE) during Cycle 1 (Up to 28 Days) that was related to LY3039478 and fulfilled any 1 of the following criterion using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI-CTCAE v 4.0): CTCAE Grade 3 non-hematological toxicity with a few exceptions, CTCAE Grade 4 hematological toxicity of greater than 5 days duration, any febrile neutropenia,Grade 3 thrombocytopenia with bleeding or Grade 4 thrombocytopenia, Any other significant toxicity deemed by the primary investigator and Lilly clinical research personnel to be dose limiting (for example, any toxicity that is possibly related to the study medication that requires the withdrawal of the participant from the study during Cycle 1).

MTD is defined as the highest tested dose that has less than 33% probability of causing a DLT during Cycle 1.

MTD is defined as the highest tested dose that has less than 33% probability of causing a DLT during Cycle 1.

Parts F1 and F2 compared loading dose three time per week with prednisone versus two times per week with prednisone. Even though the trial may have found an MTD, it did not identify an Recommended Phase 2 dose (RP2D).

Objective response is complete response (CR) + partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST 1.1 ) guidelines. CR is disappearance of all target and non-target lesions; PR is greater than or equal to (>=) 30% decrease in sum of longest diameter of target lesions. Objective response rate is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100.

Analysis Population Description: Part D: 50 mg LY3039478 (Cohort 5) was assessed using Cheson criteria. Zero participants were analyzed for Part D: 50 mg LY3039478 (Cohort 4) because data were not collected. Data was not reported because both enrolled participants discontinued treatment early-one on Day 1 due to investigator decision and the other on Day 26 due to myocardial infarction, with no efficacy assessments performed.

Parts A and B: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478

Analysis Population Description: Per Protocol, only sparse samples were analyzed for this outcome measure. There were no Sparse Day 22 samples for Part B: 50 mg & 75 mg LY3039478, Part C: 50 mg &75 LY3039478, Part D: 50 mg & 75 LY3039478 and Part E: 50 mg LY3039478

Part F1 Cohort 1 and Part F2 and Cohort 1: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478

PK: Area Under the Concentration-Time Curve From time 0 to Infinity (AUC[0-∞]) of LY3039478

Analysis Population Description: One participant assigned to the Part A: 45 mg group LY3039478 arm received 75 mg in error on Day 1 and had evaluable PK data. Therefore, this participant is included in the Part A: 75 mg LY3039478 arm PK analysis population (N=6), though only N=5 is shown in the Participant Flow module.

Part F1 Cohort1 and Part F2 Cohort 1: PK: Area Under the Concentration-Time Curve From time 0 to Infinity (AUC[0-∞]) of LY3039478

PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478

Analysis Population Description: Per protocol, AUC0-tau was not analyzed for participants undergoing sparse PK sampling. Part B 50mg participants only underwent sparse PK sampling.

PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478

Pharmacokinetics: Time to Maximum Concentration (Tmax) of LY3039478

Analysis Population Description: Per Protocol, only sparse samples were analyzed for this outcome measure. There were no Sparse Day 22 samples for Part B: 50 mg & 75 mg LY3039478, Part C: 50 mg &75 LY3039478, Part D: 50 mg & 75 LY3039478 and Part E: 50 mg LY3039478.

Part F1 Cohort1 and Part F2 Cohort 1: PK: Time to Maximum Concentration (Tmax) of LY3039478

Objective response is complete response (CR) + partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST 1.1 ) guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. Objective response rate is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100.

The time from the date of first evidence of a confirmed complete to the date of objective progression or the date of death from any cause (whichever is earlier) as classified by RECIST 1.1 guidelines. For each participant who is not known to have died or to have had a progression of disease as of the data-inclusion cut-off date, duration of response will be censored at the date of last objective response assessment prior to the date of any subsequent systemic anticancer therapy. Progressive Disease (PD) is an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if that was the smallest on study). In addition, the sum must have demonstrated an absolute increase of at least 5 mm (the appearance of 1 or more new lesions was considered progression).

Progression-free survival(PFS) time is defined as the time from the date of study enrollment to the first date of PD(symptomatic or objective) or death due to any cause,whichever occurs first.For participants who are not known to have died or progressed as of the data-inclusion cut-off date,PFS time will be censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systemic anticancer therapy. Progressive Disease(PD) is an increase of at least 20% in the sum of the diameters of target lesions,taking as reference the smallest sum on study(included baseline sum if that was the smallest on study).In addition, the sum must have demonstrated an absolute increase of at least 5 mm(the appearance of 1 or more new lesions was considered progression).

Analysis Population Description Continued:Part D:50 mg LY3039478(Cohort 4) and Part D:50 mg LY3039478(Cohort 5) were not assessed according to RECIST criteria due to their type of disease.

Overall Survival (OS) was defined as the time from the date of study enrollment 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 participants was known to be alive prior to the cut-off date.