A Study of LY3039478 in Participants With Advanced Cancer

A Phase 1 Study of LY3039478 in Patients With Advanced or Metastatic Cancer

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01695005

Enrollment

247

Registered

2012-09-27

Start date

2012-10-31

Completion date

2018-06-26

Last updated

2025-12-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Neoplasms, Neoplasm Metastasis, Lymphoma

Brief summary

The purpose of this study is to find a recommended dose level of LY3039478 that can safely be taken by participants with advanced cancer or cancer that has spread to other parts of the body, including but not limited to lymphoma. The study will also explore changes to various markers in blood cells and tissue. Finally, the study will help to document any tumor activity this drug may have.

Detailed description

In Part A of this study, participants with advanced/metastatic cancer (including lymphoma) will receive increasing doses of LY3039478 to define the dose level for Part B, C, D and E. In Part B, C, D and E LY3039478 will be explored at a predefined fixed dose level. Participants in Part B and D must have a defined alteration in a certain molecular pathway. Enrollment of participants in Part B, C, D and E will start once Part A is completed. In Part F participants will receive increasing doses of LY3039478 in combination with prednisone to define the maximum tolerated dose level.

Interventions

DRUGLY3039478

Administered orally

DRUGPrednisone

Administered orally

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* For all parts: The participant must be, in the judgment of the investigator, an appropriate candidate for experimental therapy after available standard therapies have failed to provide clinical benefit for their advanced or metastatic cancer. * For Dose Escalation (Part A): The participant must have histological or cytological evidence of cancer, either a solid tumor or a lymphoma, which is advanced or metastatic. * For Part B: All participants must have a histological evidence of their advanced or metastatic cancer and prescreened alterations in a defined pathway. * For Part C: All participants must have histological evidence of advanced or metastatic specific subtypes of soft tissue sarcoma. * For Part D: All participants must have histological evidence of advanced or metastatic cancer and prescreened alterations in a defined pathway. * Cohort 1: Participants must have triple negative breast cancer. * Cohort 2: Participants must have hepatocellular carcinoma (HCC). These participants should have Child-Pugh stage A. * Cohort 3: Participants must have cholangiocarcinoma. * Cohort 4: Participants must have chronic lymphocytic leukemia. * Cohort 5: Participants must have a mature T cell, B cell, or natural killer (NK) cell neoplasm. * For Part E: Participants must have adenoid cystic carcinoma (ACC). * For Part F dose confirmation: Participants must have leiomyosarcoma and prescreened alterations in a defined pathway. * As defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), the Revised Response Criteria for Malignant Lymphoma or the Response Assessment in Neuro Oncology (RANO) criteria for glioblastoma: * For Dose Escalation (Part A): Have measurable or nonmeasurable disease. * For Parts B, C, D, E and F: Have measurable disease or reliable biomarker measure. * For Parts B, C, D, E and F: Have available tumor tissue. * Have adequate organ function. * Have a performance status of less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) scale and life expectancy of more than 12 weeks.

Exclusion criteria

* Have symptomatic or non stable central nervous system (CNS) malignancy. * Females who are pregnant or lactating. * Have active bacterial, fungal, and/or known viral infection. * Have malabsorptive syndromes, enteropathies, gastroenteritis (acute or chronic), or diarrhea (acute or chronic). * Participants with HCC that: * Have known HCC with fibro-lamellar or mixed histology. * Have presence of clinically relevant ascites. * Have had a liver transplant. * Have active or uncontrolled clinically serious hepatitis B virus or hepatitis C virus infection.

Design outcomes

Primary

Measure	Time frame	Description
Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs)	Baseline through the end of Cycle 1, Up to 28 Days	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).
Part A: Recommended Phase 2 Dose of LY3039478 : Maximum Tolerated Dose (MTD)	Baseline though the end of cycle 1 (28 days cycle)	MTD is defined as the highest tested dose that has less than 33% probability of causing a DLT during Cycle 1.
Part B, C, D and E: Recommended Phase 2 Dose of LY3039478 : Maximum Tolerated Dose (MTD)	Baseline through the end of cycle 1 (28 days Cycle)	MTD is defined as the highest tested dose that has less than 33% probability of causing a DLT during Cycle 1.
Part F1 and F2: Recommended Phase 2 Dose of LY3039478	Baseline Up to 2 Months	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).
Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	Baseline to Disease Progression or Participant Discontinuation (Up To 20 Months)	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.

Secondary

Measure	Time frame	Description
Part F1 Cohort1 and Part F2 Cohort 1: PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478	Day 22: Predose,0.5,1,2,4,6-8,8-10,24-30 hours	PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC\[0-Tau\]) of LY3039478
Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours; Day 22: Predose,0.5,1,2,4,6-8,8-10,24-30 hours	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	Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours; Day 22: Predose,0.5,1,2,4,6-8,8-10,24-30 hours	Part F1 Cohort1 and Part F2 Cohort 1: PK: Time to Maximum Concentration (Tmax) of LY3039478
Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours; Day 22: Predose, 0.5,1,2,4,6-8,8-10,24-30 hours	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 B, C, D, E and F: Duration of Response (DoR)	Date of Complete Response or Partial Response to Date of Objective Disease Progression or Death Due to Any Cause (Up To 20 Months)	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).
Part B, C, D, E and F: Progression Free Survival (PFS)	Baseline to Objective Progression or Death from Any Cause (Up To 17 Months)	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.
Part B, C, D, E and F: Overall Survival (OS)	Baseline to Date of Death from Any Cause (Up To 49 Months)	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.
Part A: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	Baseline to Disease Progression or Participant Discontinuation (Up To 17 Months)	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.
Part F1 Cohort1 and Part F2 Cohort 1: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours; Day 22: Predose, 0.5,1,2,4,6-8,8-10,24-30 hours	Part F1 Cohort 1 and Part F2 and Cohort 1: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478
Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478	Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours	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	Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours	Part F1 Cohort1 and Part F2 Cohort 1: PK: Area Under the Concentration-Time Curve From time 0 to Infinity (AUC\[0-∞\]) of LY3039478
Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478	Day 22: Predose,0.5,1,2,4,6-8,8-10,24-30 hours	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.

Countries

Denmark, France, Germany, Spain, United Kingdom, United States

Participant flow

Pre-assignment details

Completers of the study were participants that are off treatment that did not withdraw consent and were not lost to follow up. 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.

Participants by arm

Arm	Count
Part A: 2.5 mg LY3039478 Part A: 2.5 milligrams (mg) LY3039478 administered orally three times per week (TIW) for two 28 day cycles. Participants receiving benefit may continue until disease progression.	4
Part A: 5 mg LY3039478 Part A: 5 mg LY3039478 administered orally three times per week (TIW) for two 28 day cycles. Participants receiving benefit may continue until disease progression.	3
Part A: 10 mg LY3039478 Part A: 10 mg LY3039478 administered orally three times per week (TIW) for two 28 day cycles. Participants receiving benefit may continue until disease progression.	4
Part A: 20 mg LY3039478 Part A: 20 mg LY3039478 administered orally three times per week (TIW) for two 28 day cycles. Participants receiving benefit may continue until disease progression.	8
Part A: 30 mg LY3039478 Part A: 30 mg LY3039478 administered orally three times per week (TIW) for two 28 day cycles. Participants receiving benefit may continue until disease progression.	7
Part A: 45 mg LY3039478 Part A: 45 mg LY3039478 administered orally three times per week (TIW) for two 28 day cycles. Participants receiving benefit may continue until disease progression.	5
Part A: 60 mg LY3039478 Part A: 60 mg LY3039478 administered orally three times per week (TIW) for two 28 day cycles. Participants receiving benefit may continue until disease progression.	9
Part A: 75 mg LY3039478 Part A: 75 mg LY3039478 administered orally three times per week (TIW) for two 28 day cycles. Participants receiving benefit may continue until disease progression.	5
Part A: 100 mg LY3039478 Part A: 100 mg LY3039478 administered orally three times per week (TIW) for two 28 day cycles. Participants receiving benefit may continue until disease progression.	10
Part B: 50 mg LY3039478 Part B: 50 mg LY3039478 administered orally three times per week (TIW) at a fixed dose determined in Part A for two 28 day cycles. Participants receiving benefit may continue until disease progression. Participants had tumors with molecular alterations related to Notch pathway.	30
Part B: 75 mg LY3039478 Part B: 75 mg LY3039478 administered orally three times per week (TIW) at a fixed dose determined in Part A for two 28 day cycles. Participants receiving benefit may continue until disease progression. Participants had tumors with molecular alterations related to Notch pathway.	25
Part C: 50 mg LY3039478 LMS Part C: 50 mg LY3039478 administered orally three times per week (TIW) at a fixed dose determined in Part A for two 28 day cycles. Participants receiving benefit may continue until disease progression. Participants had Leiomyosarcoma (LMS).	22
Part C: 75 mg LY3039478 LMS Part C: 75 mg LY3039478 administered orally three times per week (TIW) at a fixed dose determined in Part A for two 28 day cycles. Participants receiving benefit may continue until disease progression. Participants had Leiomyosarcoma (LMS).	6
Part C: 50 mg LY3039478 Other Sarcoma Part C: 50 mg LY3039478 administered orally three times per week (TIW) at a fixed dose determined in Part A for two 28 day cycles. Participants receiving benefit may continue until disease progression Participants had Other Sarcoma.	27
Part C: 75 mg LY3039478 Other Sarcoma Part C: 75 mg LY3039478 administered orally three times per week (TIW) at a fixed dose determined in Part A for two 28 day cycles. Participants receiving benefit may continue until disease progression Participants had Other Sarcoma.	1
Part C: 50 mg LY3039478 GIST Part C: 50 mg LY3039478 administered orally three times per week (TIW) at a fixed dose determined in Part A for two 28 day cycles. Participants receiving benefit may continue until disease progression Participants had gastrointestinal stromal tumors (GIST).	13
Part D: 75 mg LY3039478 (Cohort 1) Part D: 75 mg LY3039478 administered orally three times per week (TIW) at a fixed dose determined in Part A for two 28 day cycles. Participants receiving benefit may continue until disease progression. Participants in Triple Negative Breast Cancer cohort.	1
Part D: 75 mg LY3039478 (Cohort 3) Part D: 75 mg LY3039478 administered orally three times per week (TIW) at a fixed dose determined in Part A for two 28 day cycles. Participants receiving benefit may continue until disease progression. Participants in Cholangiocarcinoma cohort.	2
Part D: 50 mg LY3039478 (Cohort 1) Part D: 50 mg LY3039478 administered orally three times per week (TIW) at a fixed dose determined in Part A for two 28 day cycles. Participants receiving benefit may continue until disease progression. Participants in Triple Negative Breast Cancer cohort.	3
Part D: 50 mg LY3039478 (Cohort 2) Part D: 50 mg LY3039478 administered orally three times per week (TIW) at a fixed dose determined in Part A for two 28 day cycles. Participants receiving benefit may continue until disease progression. Participants in Hepatocellular Carcinoma cohort.	3
Part D: 50 mg LY3039478 (Cohort 3) Part D: 50 mg LY3039478 administered orally three times per week (TIW) at a fixed dose determined in Part A for two 28 day cycles. Participants receiving benefit may continue until disease progression. Participants in Cholangiocarcinoma cohort.	7
Part D: 50 mg LY3039478 (Cohort 4) Part D: 50 mg LY3039478 administered orally three times per week (TIW) at a fixed dose determined in Part A for two 28 day cycles. Participants receiving benefit may continue until disease progression. Participants in Chronic lymphocytic leukemia (CLL) cohort.	2
Part D: 50 mg LY3039478 (Cohort 5) Part D: 50 mg LY3039478 administered orally three times per week (TIW) at a fixed dose determined in Part A for two 28 day cycles. Participants receiving benefit may continue until disease progression. Participants in Mature T cell, B cell or Natural Killer (NK) cell neoplasms cohort.	6
Part E: LY3039478 (Cohort 1) Part E: 50 mg LY3039478 administered orally three times per week (TIW) at a fixed dose determined in Part A for two 28 day cycles. Participants receiving benefit may continue until disease progression. Participants in Triple Negative Breast Cancer cohort.	16
Part F1:Cohort1 Load75mg_50mg LY3039478 + Prednisone Part F1: Participants received a loading dose of 75 mg LY3039478 administered 3 times per week for 2 weeks during Cycle 1. 50 mg LY3039478 administered orally TIW (twice a week in cycle 1) for 28 day cycles. 20 mg Prednisone will be co-administered with LY3039478 for the first 2 weeks in cycle 1 only (28 day cycles). Participants receiving benefit may continue until disease progression.	7
Part F1:Cohort2 Load100mg_50mg LY3039478 + Prednisone Part F1: Participants received a loading dose of 100 mg LY3039478 administered 3 times per week for 2 weeks during Cycle 1. 50 mg LY3039478 administered orally TIW (twice a week in cycle 1) for 28 day cycles. 20 mg Prednisone will be co-administered with LY3039478 for the first 2 weeks in cycle 1 only (28 day cycles). Participants receiving benefit may continue until disease progression.	4
Part F2: Cohort1 Load75mg_50mg LY3039478 + Prednisone Part F2: Participants received a loading dose of 75 mg LY3039478 2 times per week for 2 weeks during Cycle 1. 50 mg LY3039478 administered orally TIW for 28 day cycles. 20 mg Prednisone will be co-administered with LY3039478 for the first 2 weeks in cycle 1 only (28 day cycles). Participants receiving benefit may continue until disease progression.	3
Part F2:Cohort2 Load100mg_50mg LY3039478 + Prednisone Part F2: Participants received a loading dose of 100 mg LY3039478 2 times per week for 2 weeks during Cycle 1. 50 mg LY3039478 administered orally TIW for 28 day cycles. 20 mg Prednisone will be co-administered with LY3039478 for the first 2 weeks in cycle 1 only (28 day cycles). Participants receiving benefit may continue until disease progression.	7
Part F2: Cohort3 Load125mg_50mg LY3039478 + Prednisone Part F2: Participants received a loading dose of 125 mg LY3039478 2 times per week for 2 weeks during Cycle 1. 50 mg LY3039478 administered orally TIW for 28 day cycles. 20 mg Prednisone will be co-administered with LY3039478 for the first 2 weeks in cycle 1 only (28 day cycles). Participants receiving benefit may continue until disease progression.	7
Total	247

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008	FG009	FG010	FG011	FG012	FG013	FG014	FG015	FG016	FG017	FG018	FG019	FG020	FG021	FG022	FG023	FG024	FG025	FG026	FG027	FG028
Overall Study	Lost to Follow-up	0	1	1	0	0	1	1	1	3	3	8	5	2	5	0	4	0	0	0	1	1	0	2	4	2	0	0	0	1
Overall Study	Withdrawal by Subject	0	0	0	2	0	1	0	1	0	1	2	1	1	0	0	0	0	0	2	0	1	0	0	0	1	0	0	1	0

Baseline characteristics

Characteristic	Part C: 75 mg LY3039478 Other Sarcoma	Part A: 5 mg LY3039478	Part A: 10 mg LY3039478	Part A: 20 mg LY3039478	Part A: 30 mg LY3039478	Part A: 45 mg LY3039478	Part A: 60 mg LY3039478	Part A: 75 mg LY3039478	Part A: 100 mg LY3039478	Part B: 50 mg LY3039478	Part B: 75 mg LY3039478	Part C: 50 mg LY3039478 LMS	Part C: 75 mg LY3039478 LMS	Part C: 50 mg LY3039478 Other Sarcoma	Part C: 50 mg LY3039478 GIST	Part D: 75 mg LY3039478 (Cohort 1)	Part D: 75 mg LY3039478 (Cohort 3)	Part D: 50 mg LY3039478 (Cohort 1)	Part D: 50 mg LY3039478 (Cohort 2)	Part D: 50 mg LY3039478 (Cohort 3)	Part D: 50 mg LY3039478 (Cohort 4)	Part D: 50 mg LY3039478 (Cohort 5)	Part E: LY3039478 (Cohort 1)	Part F1:Cohort1 Load75mg_50mg LY3039478 + Prednisone	Part F1:Cohort2 Load100mg_50mg LY3039478 + Prednisone	Part F2: Cohort1 Load75mg_50mg LY3039478 + Prednisone	Part F2:Cohort2 Load100mg_50mg LY3039478 + Prednisone	Part F2: Cohort3 Load125mg_50mg LY3039478 + Prednisone	Part A: 2.5 mg LY3039478	Total
Age, Continuous	31.0 years	52.7 years STANDARD_DEVIATION 15.5	42.8 years STANDARD_DEVIATION 14.73	58.9 years STANDARD_DEVIATION 13.37	54.9 years STANDARD_DEVIATION 16.2	58.4 years STANDARD_DEVIATION 4.72	53.2 years STANDARD_DEVIATION 7.93	59.6 years STANDARD_DEVIATION 3.97	56.6 years STANDARD_DEVIATION 12.41	55.8 years STANDARD_DEVIATION 13.45	54.3 years STANDARD_DEVIATION 11.81	55.8 years STANDARD_DEVIATION 7.08	55.3 years STANDARD_DEVIATION 13.52	60.3 years STANDARD_DEVIATION 9.01	57.9 years STANDARD_DEVIATION 9.89	35.0 years	66.5 years STANDARD_DEVIATION 9.19	52.3 years STANDARD_DEVIATION 15.04	64.0 years STANDARD_DEVIATION 8.19	55.1 years STANDARD_DEVIATION 14.18	75.0 years STANDARD_DEVIATION 7.07	53.3 years STANDARD_DEVIATION 16.84	61.3 years STANDARD_DEVIATION 10.97	60.7 years STANDARD_DEVIATION 11.12	64.8 years STANDARD_DEVIATION 6.18	45.3 years STANDARD_DEVIATION 14.15	48.1 years STANDARD_DEVIATION 10.61	53.9 years STANDARD_DEVIATION 8.86	59.8 years STANDARD_DEVIATION 8.96	56.48 years STANDARD_DEVIATION 11.63
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	2 Participants	1 Participants	2 Participants	0 Participants	2 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	17 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants	0 Participants	2 Participants	5 Participants	5 Participants	3 Participants	8 Participants	5 Participants	9 Participants	25 Participants	23 Participants	15 Participants	5 Participants	20 Participants	12 Participants	1 Participants	2 Participants	2 Participants	3 Participants	7 Participants	1 Participants	4 Participants	13 Participants	1 Participants	3 Participants	3 Participants	5 Participants	4 Participants	1 Participants	188 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	2 Participants	3 Participants	2 Participants	2 Participants	0 Participants	0 Participants	0 Participants	3 Participants	1 Participants	5 Participants	1 Participants	5 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	2 Participants	2 Participants	5 Participants	1 Participants	0 Participants	2 Participants	2 Participants	2 Participants	42 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	4 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	7 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	4 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	3 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	13 Participants
Race (NIH/OMB) White	1 Participants	3 Participants	4 Participants	8 Participants	7 Participants	5 Participants	9 Participants	4 Participants	10 Participants	29 Participants	24 Participants	16 Participants	5 Participants	26 Participants	13 Participants	1 Participants	2 Participants	2 Participants	2 Participants	7 Participants	2 Participants	3 Participants	15 Participants	4 Participants	3 Participants	3 Participants	5 Participants	5 Participants	4 Participants	222 Participants
Region of Enrollment Denmark	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	3 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	8 Participants
Region of Enrollment France	1 Participants	1 Participants	2 Participants	3 Participants	3 Participants	3 Participants	4 Participants	3 Participants	7 Participants	15 Participants	17 Participants	12 Participants	6 Participants	16 Participants	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants	1 Participants	2 Participants	6 Participants	13 Participants	6 Participants	3 Participants	3 Participants	5 Participants	5 Participants	2 Participants	142 Participants
Region of Enrollment Germany	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	4 Participants
Region of Enrollment Spain	0 Participants	2 Participants	2 Participants	5 Participants	4 Participants	2 Participants	5 Participants	2 Participants	3 Participants	6 Participants	4 Participants	3 Participants	0 Participants	4 Participants	8 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants	2 Participants	2 Participants	58 Participants
Region of Enrollment United Kingdom	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	7 Participants
Region of Enrollment United States	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	3 Participants	1 Participants	5 Participants	0 Participants	7 Participants	4 Participants	0 Participants	0 Participants	2 Participants	1 Participants	2 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	28 Participants
Sex: Female, Male Female	1 Participants	1 Participants	2 Participants	3 Participants	0 Participants	1 Participants	6 Participants	3 Participants	6 Participants	15 Participants	11 Participants	19 Participants	6 Participants	13 Participants	3 Participants	1 Participants	1 Participants	3 Participants	2 Participants	3 Participants	0 Participants	1 Participants	6 Participants	3 Participants	3 Participants	2 Participants	5 Participants	3 Participants	2 Participants	125 Participants
Sex: Female, Male Male	0 Participants	2 Participants	2 Participants	5 Participants	7 Participants	4 Participants	3 Participants	2 Participants	4 Participants	15 Participants	14 Participants	3 Participants	0 Participants	14 Participants	10 Participants	0 Participants	1 Participants	0 Participants	1 Participants	4 Participants	2 Participants	5 Participants	10 Participants	4 Participants	1 Participants	1 Participants	2 Participants	4 Participants	2 Participants	122 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk	EG012 affected / at risk	EG013 affected / at risk	EG014 affected / at risk	EG015 affected / at risk	EG016 affected / at risk	EG017 affected / at risk	EG018 affected / at risk	EG019 affected / at risk	EG020 affected / at risk	EG021 affected / at risk	EG022 affected / at risk	EG023 affected / at risk	EG024 affected / at risk	EG025 affected / at risk	EG026 affected / at risk	EG027 affected / at risk	EG028 affected / at risk
deaths Total, all-cause mortality	1 / 4	0 / 3	2 / 4	1 / 8	1 / 7	2 / 5	4 / 9	3 / 5	4 / 10	16 / 25	21 / 30	4 / 6	1 / 1	7 / 13	17 / 22	19 / 27	1 / 1	2 / 2	2 / 3	2 / 3	5 / 7	2 / 2	4 / 6	6 / 16	2 / 7	1 / 4	2 / 3	2 / 7	2 / 7
other Total, other adverse events	4 / 4	3 / 3	4 / 4	8 / 8	7 / 7	5 / 5	9 / 9	5 / 5	10 / 10	25 / 25	30 / 30	6 / 6	1 / 1	13 / 13	20 / 22	27 / 27	1 / 1	2 / 2	2 / 3	3 / 3	6 / 7	2 / 2	6 / 6	16 / 16	7 / 7	4 / 4	3 / 3	7 / 7	7 / 7
serious Total, serious adverse events	1 / 4	0 / 3	2 / 4	4 / 8	5 / 7	3 / 5	5 / 9	1 / 5	5 / 10	14 / 25	14 / 30	5 / 6	1 / 1	8 / 13	8 / 22	10 / 27	0 / 1	2 / 2	2 / 3	1 / 3	2 / 7	2 / 2	3 / 6	8 / 16	3 / 7	2 / 4	2 / 3	4 / 7	5 / 7

Outcome results

Primary

Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs)

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).

Time frame: Baseline through the end of Cycle 1, Up to 28 Days

Population: All Part A and F participants who received at least one dose of study drug.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Part A: 2.5 mg LY3039478	Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs)	0 Participants
Part A: 5 mg LY3039478	Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs)	0 Participants
Part A: 10 mg LY3039478	Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs)	0 Participants
Part A: 20 mg LY3039478	Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs)	1 Participants
Part A: 30 mg LY3039478	Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs)	1 Participants
Part A: 45 mg LY3039478	Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs)	0 Participants
Part A: 60 mg LY3039478	Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs)	2 Participants
Part A: 75 mg LY3039478	Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs)	0 Participants
Part A: 100 mg LY3039478	Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs)	2 Participants
Part F1:Cohort1 Load75mg_50mg LY3039478 + Prednisone	Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs)	1 Participants
Part F1:Cohort2 Load100mg_50mg LY3039478 + Prednisone	Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs)	2 Participants
Part F2: Cohort1 Load75mg_50mg LY3039478 + Prednisone	Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs)	0 Participants
Part F2:Cohort2 Load100mg_50mg LY3039478 + Prednisone	Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs)	0 Participants
Part F2: Cohort3 Load125mg_50mg LY3039478 + Prednisone	Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs)	2 Participants

Primary

Part A: Recommended Phase 2 Dose of LY3039478 : Maximum Tolerated Dose (MTD)

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

Time frame: Baseline though the end of cycle 1 (28 days cycle)

Population: All part A participants who received at least one dose of study drug.

Arm	Measure	Value (NUMBER)
Part A: 2.5 mg LY3039478	Part A: Recommended Phase 2 Dose of LY3039478 : Maximum Tolerated Dose (MTD)	75 milligram (mg)

Primary

Part B, C, D and E: Recommended Phase 2 Dose of LY3039478 : Maximum Tolerated Dose (MTD)

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

Time frame: Baseline through the end of cycle 1 (28 days Cycle)

Population: All part B, C, D and E participants who received at least one dose of study drug.

Arm	Measure	Value (NUMBER)
Part A: 2.5 mg LY3039478	Part B, C, D and E: Recommended Phase 2 Dose of LY3039478 : Maximum Tolerated Dose (MTD)	50 milligram (mg)

Primary

Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])

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.

Time frame: Baseline to Disease Progression or Participant Discontinuation (Up To 20 Months)

Population: All Part B, C, D, E and F participants who received at least one dose of study drug and who had evaluable responses.

Arm	Measure	Value (NUMBER)
Part A: 2.5 mg LY3039478	Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part A: 5 mg LY3039478	Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part A: 10 mg LY3039478	Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part A: 20 mg LY3039478	Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part A: 30 mg LY3039478	Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part A: 45 mg LY3039478	Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part A: 60 mg LY3039478	Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part A: 75 mg LY3039478	Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part A: 100 mg LY3039478	Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part F1:Cohort1 Load75mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part F1:Cohort2 Load100mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part F2: Cohort1 Load75mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part F2: Cohort3 Load125mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	16.7 percentage of participants
Part E: LY3039478 (Cohort 1)	Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part F1:Cohort1 Load75mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part F1:Cohort2 Load100mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part F2: Cohort1 Load75mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part F2:Cohort2 Load100mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part F2: Cohort3 Load125mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants

Primary

Part F1 and F2: Recommended Phase 2 Dose of LY3039478

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).

Time frame: Baseline Up to 2 Months

Population: All Part F1 and F2 participants who received at least one dose of study drug.

Arm	Measure	Value (NUMBER)
Part A: 2.5 mg LY3039478	Part F1 and F2: Recommended Phase 2 Dose of LY3039478	NA milligram (mg)

Secondary

Part A: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])

Time frame: Baseline to Disease Progression or Participant Discontinuation (Up To 17 Months)

Population: All Part A participants who received at least one dose of study drug and who had evaluable responses.

Arm	Measure	Value (NUMBER)
Part A: 2.5 mg LY3039478	Part A: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part A: 5 mg LY3039478	Part A: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part A: 10 mg LY3039478	Part A: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part A: 20 mg LY3039478	Part A: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part A: 30 mg LY3039478	Part A: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part A: 45 mg LY3039478	Part A: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part A: 60 mg LY3039478	Part A: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part A: 75 mg LY3039478	Part A: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	0 percentage of participants
Part A: 100 mg LY3039478	Part A: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	10 percentage of participants

Secondary

Part B, C, D, E and F: Duration of Response (DoR)

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).

Time frame: Date of Complete Response or Partial Response to Date of Objective Disease Progression or Death Due to Any Cause (Up To 20 Months)

Population: All participants who received at least one dose of the drug and had evaluable responses were included. Since there were no participants with a complete response (CR) or partial response (PR), the duration of response could not be analyzed for any cohort except Part D: 50 mg LY3039478 (Cohort 5)

Arm	Measure	Value (MEDIAN)
Part F2: Cohort3 Load125mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Duration of Response (DoR)	4.7 months

Secondary

Part B, C, D, E and F: Overall Survival (OS)

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.

Time frame: Baseline to Date of Death from Any Cause (Up To 49 Months)

Population: All Part B, C, D, E and F participants who received at least one dose of study drug. Participants censored were: Part B: 9, 9; Part C: 5, 2, 8, 0, 6; Part D: 0, 0,1, 1, 2, 0, 2; Part E:10; Part F1: 5, 3; Part F2:1, 5, 5 in order of arms above. Censored participants were included in the analysis.

Arm	Measure	Value (MEDIAN)
Part A: 2.5 mg LY3039478	Part B, C, D, E and F: Overall Survival (OS)	7.29 months
Part A: 5 mg LY3039478	Part B, C, D, E and F: Overall Survival (OS)	8.94 months
Part A: 10 mg LY3039478	Part B, C, D, E and F: Overall Survival (OS)	9.46 months
Part A: 20 mg LY3039478	Part B, C, D, E and F: Overall Survival (OS)	12.80 months
Part A: 30 mg LY3039478	Part B, C, D, E and F: Overall Survival (OS)	6.21 months
Part A: 45 mg LY3039478	Part B, C, D, E and F: Overall Survival (OS)	2.20 months
Part A: 60 mg LY3039478	Part B, C, D, E and F: Overall Survival (OS)	16.53 months
Part A: 75 mg LY3039478	Part B, C, D, E and F: Overall Survival (OS)	10.32 months
Part A: 100 mg LY3039478	Part B, C, D, E and F: Overall Survival (OS)	6.52 months
Part F1:Cohort1 Load75mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Overall Survival (OS)	1.59 months
Part F1:Cohort2 Load100mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Overall Survival (OS)	15.51 months
Part F2: Cohort1 Load75mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Overall Survival (OS)	8.64 months
Part F2:Cohort2 Load100mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Overall Survival (OS)	5.90 months
Part F2: Cohort3 Load125mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Overall Survival (OS)	9.00 months
Part E: LY3039478 (Cohort 1)	Part B, C, D, E and F: Overall Survival (OS)	NA months
Part F1:Cohort1 Load75mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Overall Survival (OS)	NA months
Part F1:Cohort2 Load100mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Overall Survival (OS)	NA months
Part F2: Cohort1 Load75mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Overall Survival (OS)	9.40 months
Part F2:Cohort2 Load100mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Overall Survival (OS)	NA months
Part F2: Cohort3 Load125mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Overall Survival (OS)	NA months

Secondary

Part B, C, D, E and F: Progression Free Survival (PFS)

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.

Time frame: Baseline to Objective Progression or Death from Any Cause (Up To 17 Months)

Population: All Part B, C, D, E and F participants who received at least one dose of study drug. Participants censored were: Part B: 4, 3 ; Part C: 2,1, 3,0,1; Part D: 0, 0, 1, 1, 1; Part E: 2; Part F1: 0,1; Part F2: 0,1,1 in order of arms above. Censored participants were included in the analysis.

Arm	Measure	Value (MEDIAN)
Part A: 2.5 mg LY3039478	Part B, C, D, E and F: Progression Free Survival (PFS)	1.77 months
Part A: 5 mg LY3039478	Part B, C, D, E and F: Progression Free Survival (PFS)	1.84 months
Part A: 10 mg LY3039478	Part B, C, D, E and F: Progression Free Survival (PFS)	1.76 months
Part A: 20 mg LY3039478	Part B, C, D, E and F: Progression Free Survival (PFS)	3.61 months
Part A: 30 mg LY3039478	Part B, C, D, E and F: Progression Free Survival (PFS)	1.66 months
Part A: 45 mg LY3039478	Part B, C, D, E and F: Progression Free Survival (PFS)	1.68 months
Part A: 60 mg LY3039478	Part B, C, D, E and F: Progression Free Survival (PFS)	1.86 months
Part A: 75 mg LY3039478	Part B, C, D, E and F: Progression Free Survival (PFS)	0.95 months
Part A: 100 mg LY3039478	Part B, C, D, E and F: Progression Free Survival (PFS)	1.38 months
Part F1:Cohort1 Load75mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Progression Free Survival (PFS)	0.66 months
Part F1:Cohort2 Load100mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Progression Free Survival (PFS)	1.68 months
Part F2: Cohort1 Load75mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Progression Free Survival (PFS)	2.22 months
Part E: LY3039478 (Cohort 1)	Part B, C, D, E and F: Progression Free Survival (PFS)	4.67 months
Part F1:Cohort1 Load75mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Progression Free Survival (PFS)	3.25 months
Part F1:Cohort2 Load100mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Progression Free Survival (PFS)	2.05 months
Part F2: Cohort1 Load75mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Progression Free Survival (PFS)	3.52 months
Part F2:Cohort2 Load100mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Progression Free Survival (PFS)	2.10 months
Part F2: Cohort3 Load125mg_50mg LY3039478 + Prednisone	Part B, C, D, E and F: Progression Free Survival (PFS)	4.04 months

Secondary

Part F1 Cohort1 and Part F2 Cohort 1: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478

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

Time frame: Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours; Day 22: Predose, 0.5,1,2,4,6-8,8-10,24-30 hours

Population: All participants who received at least one dose of study drug and had evaluable PK data from intensive PK sampling (Part F1 Cohort 1 and Part F2: Cohort 1 reporting Arms/Groups). No PK parameters are reported for participants who received loading doses of 100 (Part F1:Cohort2, Part F2:Cohort2 reporting arms) and 125mg (Part F2: Cohort3 reporting arm) on Day 1, because PK samples were not available for bioanalysis.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part A: 2.5 mg LY3039478	Part F1 Cohort1 and Part F2 Cohort 1: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 1, 75 mg	1450 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 39
Part A: 2.5 mg LY3039478	Part F1 Cohort1 and Part F2 Cohort 1: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 22, 50 mg	NA nanograms per millilitre (ng/mL)	—
Part A: 5 mg LY3039478	Part F1 Cohort1 and Part F2 Cohort 1: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 1, 75 mg	1030 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 49
Part A: 5 mg LY3039478	Part F1 Cohort1 and Part F2 Cohort 1: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 22, 50 mg	765 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 89

Secondary

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

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

Time frame: Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours

Population: All participants who received at least one dose of study drug and had evaluable PK data from intensive PK sampling (Part F1 and Part F2). No PK parameters are reported for participants who received loading doses of 100 (Part F1:Cohort2, Part F2:Cohort2 reporting arms) and 125mg (Part F2: Cohort3 reporting arm) on Day 1, because PK samples were not available for bioanalysis.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part A: 2.5 mg LY3039478	Part F1 Cohort1 and Part F2 Cohort 1: PK: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478	5440 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 70
Part A: 5 mg LY3039478	Part F1 Cohort1 and Part F2 Cohort 1: PK: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478	4410 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 53

Secondary

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

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

Time frame: Day 22: Predose,0.5,1,2,4,6-8,8-10,24-30 hours

Population: All participants who received at least one dose of study drug and had evaluable PK data from intensive PK sampling (100 mg (Part F1:Cohort2, Part F2:Cohort2 reporting arms) and 125mg (Part F2: Cohort3 reporting arm)). No PK parameters are reported for participants who received loading doses of 100 and 125mg on Day 1, because PK samples were not available for bioanalysis.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part A: 2.5 mg LY3039478	Part F1 Cohort1 and Part F2 Cohort 1: PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478	NA nanogramshour per milliliter (ngh/mL)	—
Part A: 5 mg LY3039478	Part F1 Cohort1 and Part F2 Cohort 1: PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478	3430 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 101

Secondary

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

Time frame: Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours; Day 22: Predose,0.5,1,2,4,6-8,8-10,24-30 hours

Arm	Measure	Group	Value (MEDIAN)
Part A: 2.5 mg LY3039478	Part F1 Cohort1 and Part F2 Cohort 1: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 22, 50 mg	NA Hours (h)
Part A: 2.5 mg LY3039478	Part F1 Cohort1 and Part F2 Cohort 1: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 1, 75 mg	1.02 Hours (h)
Part A: 5 mg LY3039478	Part F1 Cohort1 and Part F2 Cohort 1: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 1, 75 mg	1.03 Hours (h)
Part A: 5 mg LY3039478	Part F1 Cohort1 and Part F2 Cohort 1: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 22, 50 mg	2.00 Hours (h)

Secondary

Parts A and B: 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 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.

Time frame: Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours

Population: All Participants who received at least one dose of study drug and had evaluable PK data from intensive PK sampling. No PK parameters are reported for participants who did not undergo intensive PK sampling (including Part B 50mg, some participants in Part B 75mg).

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part A: 2.5 mg LY3039478	Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478	98.4 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 64
Part A: 5 mg LY3039478	Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478	282 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 53
Part A: 10 mg LY3039478	Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478	412 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 84
Part A: 20 mg LY3039478	Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478	1410 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 51
Part A: 30 mg LY3039478	Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478	1590 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 70
Part A: 45 mg LY3039478	Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478	1250 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 10
Part A: 60 mg LY3039478	Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478	4030 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 66
Part A: 75 mg LY3039478	Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478	4270 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 43
Part A: 100 mg LY3039478	Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478	NA nanogramshour per milliliter (ngh/mL)	—
Part F1:Cohort1 Load75mg_50mg LY3039478 + Prednisone	Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478	3870 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 45
Part F1:Cohort2 Load100mg_50mg LY3039478 + Prednisone	Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478	6420 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 47

Secondary

Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) 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.

Time frame: Day 22: Predose,0.5,1,2,4,6-8,8-10,24-30 hours

Population: All Participants who received at least one dose of study drug and had evaluable PK data from intensive PK sampling. Sampling was conducted in all Part A participants \& only a subset of participants in Part B at 75 mg. No PK parameters are reported for participants who did not undergo intensive PK sampling (including Part B 50mg, some participants in Part B 75mg).

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part A: 2.5 mg LY3039478	Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478	NA nanogramshour per milliliter (ngh/mL)	—
Part A: 5 mg LY3039478	Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478	290 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 33
Part A: 10 mg LY3039478	Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478	585 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 90
Part A: 20 mg LY3039478	Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478	1170 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 38
Part A: 30 mg LY3039478	Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478	1290 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 71
Part A: 45 mg LY3039478	Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478	3220 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 57
Part A: 60 mg LY3039478	Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478	2530 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 37
Part A: 75 mg LY3039478	Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478	3350 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 78
Part A: 100 mg LY3039478	Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478	2830 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 23
Part F1:Cohort1 Load75mg_50mg LY3039478 + Prednisone	Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478	3900 nanogramshour per milliliter (ngh/mL)	Geometric Coefficient of Variation 90

Secondary

Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478

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

Time frame: Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours; Day 22: Predose, 0.5,1,2,4,6-8,8-10,24-30 hours

Population: All Participants who received at least one dose of study drug and had evaluable PK data from intensive PK sampling. 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 5 are shown in the Participant Flow module.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part A: 2.5 mg LY3039478	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 1	13.5 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 47
Part A: 2.5 mg LY3039478	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 22	NA nanograms per millilitre (ng/mL)	—
Part A: 5 mg LY3039478	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 1	36.0 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 29
Part A: 5 mg LY3039478	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 22	38.0 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 34
Part A: 10 mg LY3039478	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 22	81.9 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 87
Part A: 10 mg LY3039478	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 1	63.1 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 58
Part A: 20 mg LY3039478	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 1	220 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 57
Part A: 20 mg LY3039478	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 22	175 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 28
Part A: 30 mg LY3039478	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 1	288 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 46
Part A: 30 mg LY3039478	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 22	191 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 60
Part A: 45 mg LY3039478	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 22	522 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 28
Part A: 45 mg LY3039478	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 1	264 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 19
Part A: 60 mg LY3039478	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 22	516 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 57
Part A: 60 mg LY3039478	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 1	657 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 63
Part A: 75 mg LY3039478	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 22	444 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 55
Part A: 75 mg LY3039478	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 1	760 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 61
Part A: 100 mg LY3039478	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 22	770 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 72
Part A: 100 mg LY3039478	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 1	1100 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 36
Part F1:Cohort1 Load75mg_50mg LY3039478 + Prednisone	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 1	426 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 70.5
Part F1:Cohort2 Load100mg_50mg LY3039478 + Prednisone	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 1	664 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 53.4
Part F2: Cohort1 Load75mg_50mg LY3039478 + Prednisone	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 1	389 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 60.2
Part F2:Cohort2 Load100mg_50mg LY3039478 + Prednisone	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 1	725 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 58.5
Part F2: Cohort3 Load125mg_50mg LY3039478 + Prednisone	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 1	511 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 39.1
Part E: LY3039478 (Cohort 1)	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 1	533 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 35.2
Part F1:Cohort1 Load75mg_50mg LY3039478 + Prednisone	Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478	Day 1	401 nanograms per millilitre (ng/mL)	Geometric Coefficient of Variation 38.1

Secondary

Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) 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.

Time frame: Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours; Day 22: Predose,0.5,1,2,4,6-8,8-10,24-30 hours

Population: All Participants who received at least one dose of study drug and had evaluable PK data from intensive PK sampling. 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 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.

Arm	Measure	Group	Value (MEDIAN)
Part A: 2.5 mg LY3039478	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 1	1.52 Hours (h)
Part A: 2.5 mg LY3039478	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 22	NA Hours (h)
Part A: 5 mg LY3039478	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 1	2.00 Hours (h)
Part A: 5 mg LY3039478	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 22	2.00 Hours (h)
Part A: 10 mg LY3039478	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 22	2.00 Hours (h)
Part A: 10 mg LY3039478	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 1	1.50 Hours (h)
Part A: 20 mg LY3039478	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 1	1.87 Hours (h)
Part A: 20 mg LY3039478	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 22	2.00 Hours (h)
Part A: 30 mg LY3039478	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 1	2.00 Hours (h)
Part A: 30 mg LY3039478	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 22	2.00 Hours (h)
Part A: 45 mg LY3039478	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 22	1.00 Hours (h)
Part A: 45 mg LY3039478	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 1	1.03 Hours (h)
Part A: 60 mg LY3039478	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 22	1.00 Hours (h)
Part A: 60 mg LY3039478	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 1	2.00 Hours (h)
Part A: 75 mg LY3039478	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 22	2.05 Hours (h)
Part A: 75 mg LY3039478	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 1	1.56 Hours (h)
Part A: 100 mg LY3039478	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 22	1.00 Hours (h)
Part A: 100 mg LY3039478	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 1	2.00 Hours (h)
Part F1:Cohort1 Load75mg_50mg LY3039478 + Prednisone	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 1	2.00 Hours (h)
Part F1:Cohort2 Load100mg_50mg LY3039478 + Prednisone	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 1	1.92 Hours (h)
Part F2: Cohort1 Load75mg_50mg LY3039478 + Prednisone	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 1	2.00 Hours (h)
Part F2:Cohort2 Load100mg_50mg LY3039478 + Prednisone	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 1	1.00 Hours (h)
Part F2: Cohort3 Load125mg_50mg LY3039478 + Prednisone	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 1	2.00 Hours (h)
Part E: LY3039478 (Cohort 1)	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 1	1.08 Hours (h)
Part F1:Cohort1 Load75mg_50mg LY3039478 + Prednisone	Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478	Day 1	2.00 Hours (h)

Source: ClinicalTrials.gov · Data processed: Mar 4, 2026

A Study of LY3039478 in Participants With Advanced Cancer

Conditions

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs)

Part A: Recommended Phase 2 Dose of LY3039478 : Maximum Tolerated Dose (MTD)

Part B, C, D and E: Recommended Phase 2 Dose of LY3039478 : Maximum Tolerated Dose (MTD)

Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])

Part F1 and F2: Recommended Phase 2 Dose of LY3039478

Part A: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])

Part B, C, D, E and F: Duration of Response (DoR)

Part B, C, D, E and F: Overall Survival (OS)

Part B, C, D, E and F: Progression Free Survival (PFS)

Part F1 Cohort1 and Part F2 Cohort 1: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478

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

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

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

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

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

Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478

Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478