A Study of LY2157299 in Participants With Hepatocellular Carcinoma

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01246986
• Collaborator: (none)
• Enrollment: 204
• Locations: 40
• Arms: 7
• Actual Duration (Months): 104.8
• Patients Per Site: 5.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to estimate the median time to progression in participants with hepatocellular carcinoma (HCC) when treated with LY2157299 as monotherapy and in combination with sorafenib or ramucirumab.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Hepatocellular	Drug: LY2157299; Drug: Sorafenib; Drug: Ramucirumab	Phase 2

Detailed Description

The study consists of four Parts: Part A where HCC participants with an increased alpha-fetoprotein (AFP) level will be treated with either 160 milligrams (mg) LY2157299 or 300 mg LY2157299. Part B where HCC participants with a normal AFP level will be treated with 300 mg LY2157299, Part C where treatment-naïve HCC participants will be treated with 160 mg LY2157299 + sorafenib or 300 mg LY2157299 + sorafenib, and Part D where HCC participants will be treated with either 160 mg or 300 mg LY2157299 + ramucirumab.

Participants who continue to receive benefit from treatment at the time that the study is considered completed, may enter the treatment extension period and continue to receive the study treatment. The end of the study is the date of last visit or last scheduled procedure for the last active subject in the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 204 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study of LY2157299 in Patients With Hepatocellular Carcinoma
• Actual Study Start Date: Mar 30, 2011
• Actual Primary Completion Date: Jun 6, 2019
• Actual Study Completion Date: Dec 24, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A Cohort 1-160 milligram (mg) LY2157299 Per the protocol, following an interim analysis, the decision was taken to no longer randomize participants to the 160 mg LY2157299 arm. As of May 25,2012, all newly enrolled participants will receive 300 mg LY2157299. 80 mg LY2157299 given orally twice daily (BID) for 14 days followed by 14 days off (28-day cycle). Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.	Drug: LY2157299; Administered orally
Experimental: Part A Cohort 2 - 300 mg LY2157299 150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle). Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.	Drug: LY2157299; Administered orally; Drug: Sorafenib; Administered orally
Experimental: Part B - 300 mg LY2157299 150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle). Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.	Drug: LY2157299; Administered orally
Experimental: Part C Cohort 1 - 160 mg LY2157299 + 800 mg Sorafenib 80 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle). Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.	Drug: LY2157299; Administered orally; Drug: Sorafenib; Administered orally
Experimental: Part C Cohort 2 - 300 mg LY2157299 + 800 mg Sorafenib 150 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle). Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.	Drug: LY2157299; Administered orally; Drug: Sorafenib; Administered orally
Experimental: Part D Cohort 1 - 160 mg LY2157299 + 8 mg/kg Ramucirumab 80 mg LY2157299 given orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kilogram (kg) intravenous (IV) on days 1 and 15 (28-day cycle). Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.	Drug: LY2157299; Administered orally; Drug: Ramucirumab; Administered IV; Other Names: LY30098016
Experimental: Part D Cohort 2 - 300 mg LY2157299 + 8 mg/kg Ramucirumab 150 mg LY2157299 given orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kg IV on days 1 and 15 (28-day cycle). Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.	Drug: LY2157299; Administered orally; Drug: Ramucirumab; Administered IV; Other Names: LY30098016

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Relationship of Biomarker Alpha-fetoprotein (AFP) to Overall Survival (OS) [Baseline, discontinuation from any cause (Up to 83 months)]

   Biomarker response was defined as a > 20% decrease in the biomarker AFP from baseline during 8 weeks of treatment. Data presented is median overall survival of those participants who achieved the defined biomarker response. Participants enrolled in Part A had a baseline AFP level of >1.5 upper limit normal (ULN). Participants enrolled in Part B had baseline AFP level <1.5 ULN.

2. Change From Baseline in Relationship of Biomarker Transforming Growth Factor - Beta (TGF-β) to Overall Survival (OS) [Baseline,discontinuation from any cause (Up to 83 months)]

   Biomarker response was defined as a > 20% decrease in the biomarker TGF-B from baseline. Data presented is median overall survival of those participants who achieved biomarker response.

3. Time to Progression (TTP) [Randomization to date of first measured progressive disease (Up to 36 Weeks)]

   TTP is measured from the date of first dose to the first date of progression of disease based on the investigator review of tumor response using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Progression is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.

Secondary Outcome Measures

1. Population Pharmacokinetics (PK) Mean Population Clearance of Galunisertib [Cycle (C) 1: Day (D)1: Predose, 0.5-2 hours(h) Postdose; D14: Predose, 0.5-2, 3-5 h, Postdose; D15 Morning; D22 Morning; Predose C2 and C3 Predose D1]

   Population mean (between-subject coefficient variance [CV %]) apparent clearance.

2. Recommended Dose for Phase 3 Hepatocellular Carcinoma (HCC) Trials [Cycle 1 (28 Days)]

3. Overall Survival (OS) [Randomization to date of death from any cause (Up to 83 months)]

   OS duration is measured from the date of first dose to the date of death from any cause.

4. Progression Free Survival (PFS) [Randomization to measured progressive disease or death from any cause (Up to 45 Weeks)]

   PFS duration is measure from the date of first dose to the first date of objective progression of disease or death from any cause. Progression is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.

5. Percentage of Participants Achieving an Objective Response (Response Rate) [Randomization to measured progressive disease (Up to 36 Weeks)]

   The percentage of participants who achieved best overall response of either Complete Response (CR) or Partial Response (PR). The overall response rate for each dose with be estimated by dividing the number of confirmed responders by the number of participants who received at least one dose of study drug. Per RECIST v.1.0 criteria CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 millimeter (mm). Tumor-marker results must have normalized. PR is defined as at least 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters.

6. Duration of Tumor Response (DoR) [Time of response to measured progressive disease or death from any cause (Up to 84 Weeks)]

   DoR is measured from the date of the first objective status assessment of a Complete Response (CR) or Partial Response (PR), as determined by RECIST v1.1, to the first date of objective progression of disease or death from any cause. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 millimeter (mm). Tumor-marker results must have normalized. PR is defined as at least 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progression is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.

7. Time to Treatment Failure (TTF) [Randomization to the date of discontinuation of study treatment due to adverse event, progression of disease, or death from any cause (Up to 75 Weeks)]

   TTF is measured from the date of first dose until the date of discontinuation of study treatment due to adverse event, progression of disease, or death from any cause.

8. Change From Baseline in Functional Assessment of Cancer Therapy, Hepatobiliary (FACT-Hep) Sub-scores and Total Score [Baseline, Day 1 Cycle 4]

   FACT-Hep consists of 45 items in five subscales (1) physical well-being (PWB) score rage 0 -28; (2) social well-being (SWB) score range 0-28; (3) emotional well-being (EWB) score range 0-24; (4) functional well-being (FWB) score range 0-28; and (5) the hepatobiliary cancer subscale (HCS) Score range 0-72; FACT-Hep score range 1-180, and Trial-Outcome Index (TOI) score range 1-128, to assess health related quality of life in participants with cancer. Higher scores reflect a better health state.

9. Time to Worsening (TTW) of Symptoms (FACT-Hep) [Baseline to the worsening of symptoms (up to 567 days)]

   Time to worsening of symptoms used minimally important differences to evaluate Physical Well Being (PWB), Functional Well Being (FWB), Hepatocellular Cancer Symptoms (HCS), National Comprehensive Cancer Network (NCCN)/FACT Hepatocellular Symptoms (FHS), Trial-Outcome Index (TOI). PWB time to worsening was defined as participants who had change in a subscale of ≥ 2 point decrease from baseline; FWB time to worsening was defined as participants who had change in a subscale of ≥ 2 point decrease from baseline; HCS time to worsening was defined as participants who had change in a subscale of ≥ 5 point decrease from baseline; FHS time to worsening was defined as participants who had change in a subscale of ≥ 2 point decrease from baseline; TOI time to Worsening was defined as participants who had change in the subscale of ≥ 7 point decrease from baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have histological evidence of a diagnosis of HCC not amenable to curative surgery

• Part A: Serum alpha fetoprotein greater than or equal to 1.5 Upper Limits of Normal, Part B: Serum alpha fetoprotein less than 1.5 Upper Limits of Normal. Not applicable for Part C or D

• Child-Pugh Stage: A or B7 for Parts A & B, A for Part C, and D

• Have the presence of measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). A lesion that has been previously treated by local therapy will qualify as a measurable or evaluable lesion if there was demonstrable progression following locoregional therapy

• Have given written informed consent prior to any study-specific procedures

• Have adequate hematologic, hepatic and renal function

• Have a performance status of equal to or less than 1 on the Eastern Cooperative Oncology Group (ECOG) scale

• For Parts A & B: Have received sorafenib and have progressed or were intolerant to sorafenib or are ineligible for sorafenib treatment. For Part C: not received previous systemic treatment. For Part D: have received sorafenib and have progressed or were intolerant to sorafenib or are ineligible for sorafenib treatment or have not received prior systemic treatment.

• For Parts A, B, and D: have discontinued sorafenib for at least 2 weeks

• Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures

• Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug

• Females with childbearing potential must have had a negative serum pregnancy test less than or equal to 7 days prior to the first dose of study drug

• Are able to swallow capsules or tablets

Exclusion Criteria:

• Are currently enrolled in, or discontinued within the last 28 days from a clinical trial involving an investigational drug or device or not approved use of a drug or device (other than the study drug used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

• Known HCC with fibro-lamellar or mixed histology

• Presence of clinically relevant ascites

• History of liver transplant requiring increased immunosuppressive therapy. (Participants on maintenance immunosuppressive therapy after liver transplant are eligible for Part A & B)

• Have received more than 1 line of systemic treatment in Parts A, B and D

• Have moderate or severe cardiac disease:

1. Have the presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association (NYHA) Class III/IV congestive heart failure, or uncontrolled hypertension

2. Have documented major electrocardiogram (ECG) abnormalities at the investigator's discretion

3. Have major abnormalities documented by echocardiography with Doppler

4. Have predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress

• Have serious preexisting medical conditions that, in the opinion of the investigator, that cannot be adequately controlled with appropriate therapy or would preclude participation in this study

• Females who are pregnant or lactating

• Have a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix) unless in complete remission and off all therapy for that disease for a minimum of 3 years. At the discretion of the investigator, hormone-refractory prostate cancer participants who are stable on GnRH agonist therapy and breast cancer participants who are stable on antiestrogen therapy may have that treatment continued

• Have active infection that would interfere with the study objectives or influence study compliance

• For Part C, have a known hypersensitivity to sorafenib or its excipients

• For Part D, have a serious illness or medical condition(s), including but not limited to the following:

1. The participant has undergone major surgery within 28 days prior to randomization or has undergone central venous access device placement within 7 days prior to randomization

2. The participant has uncontrolled arterial hypertension ≥150 / ≥90 millimeters of mercury (mm Hg) despite standard medical management

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Highlands Oncology Group	Fayetteville	Arkansas	United States	72703
2	University of California, San Francisco	San Francisco	California	United States	94158
3	Georgetown University Medical Center	Washington	District of Columbia	United States	20007
4	MD Anderson Cancer Center Orlando	Orlando	Florida	United States	32806
5	Northwestern University	Chicago	Illinois	United States	60611
6	Indiana Univ Melvin & Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
7	Lahey Clinic Medical Center	Burlington	Massachusetts	United States	01805
8	Weill Cornell Medical College	New York	New York	United States	10021
9	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
10	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nedlands	Western Australia	Australia	6009
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Greenslopes		Australia	4120
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Heidelberg		Australia	3084
14	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	St. Leonards		Australia	2065
15	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Brest		France	29609
16	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Caen		France	14033
17	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Clichy		France	92110
18	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Creteil		France	94010
19	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lille		France	59037
20	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lyon		France	69317
21	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Marseille		France	13273
22	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Montpellier		France	34295
23	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Paris		France	75012
24	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Pessac		France	33604
25	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Saint Etienne		France	42055
26	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Saint Herblain		France	44805
27	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Strasbourg		France	67085
28	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Vandoeuvre Les Nancy		France	54511
29	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Berlin		Germany	13353
30	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Erlangen		Germany	91054
31	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Göttingen		Germany	37075
32	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Köln		Germany	50937
33	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Mainz		Germany	55131
34	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Münster		Germany	48149
35	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bari		Italy	70124
36	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Rome		Italy	00168
37	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Rozzano		Italy	20089
38	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Auckland		New Zealand	1023
39	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Barcelona		Spain	08035
40	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Madrid		Spain	28007

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

• Study Protocol - Aug 18, 2016
• Statistical Analysis Plan - Oct 11, 2013

More Information

Additional Information:

• A Study of LY2157299 in Participants With Hepatocellular Carcinoma

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01246986
• Other Study ID Numbers: 13665; H9H-MC-JBAK; 2010-022338-10
• First Posted: Nov 24, 2010
• Last Update Posted: Jan 12, 2021
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Sorafenib; Ramucirumab

Study Results

Participant Flow

Pre-assignment Detail	Participants who had progressive disease or death are defined as completed. Per the protocol, following an interim analysis, the decision was taken to no longer randomize participants to the 160 mg LY2157299 arm.

Arm/Group Title	Part A Cohort 1 - 160 mg LY2157299	Part A Cohort 2 - 300 mg LY2157299	Part B - 300 mg LY2157299	Part C Cohort 1 - 160 mg LY2157299 + Sorafenib	Part C Cohort 2 - 300 mg LY2157299 + Sorafenib	Part D Cohort 1 - 160 mg LY2157299 + Ramucirumab	Part D Cohort 2 - 300 mg LY2157299 + Ramucirumab
Arm/Group Description	80 mg LY2157299 given orally twice daily (BID) for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	80 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).	150 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).	80 mg LY2157299 given orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kilogram (kg) intravenous (IV) on days 1 and 15 (28-day cycle).	150 mg LY2157299 given twice orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kg IV on days 1 and 15 (28-day cycle).
Period Title: Overall Study
STARTED	37	72	40	3	44	3	5
Received at Least 1 Dose of Study Drug	37	72	40	3	44	3	5
COMPLETED	34	67	34	3	40	2	5
NOT COMPLETED	3	5	6	0	4	1	0

Baseline Characteristics

Arm/Group Title	Part A Cohort 1 - 160 mg LY2157299	Part A Cohort 2 - 300 mg LY2157299	Part B - 300 mg LY2157299	Part C Cohort 1 - 160 mg LY2157299 + Sorafenib	Part C Cohort 2 - 300 mg LY2157299 + Sorafenib	Part D Cohort 1 - 160 mg LY2157299 + Ramucirumab	Part D Cohort 2 - 300 mg LY2157299 + Ramucirumab	Total
Arm/Group Description	80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle)..	150mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	80 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).	150 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).	80 mg LY2157299 given orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kilogram (kg) intravenous (IV) on days 1 and 15 (28-day cycle).	150 mg LY2157299 given twice BID on days 1 to 14 in combination with ramucirumab 8 mg/kg IV on days 1 and 15 (28-day cycle).	Total of all reporting groups
Overall Participants	37	72	40	3	44	3	5	204
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.4 (10.8)	63.3 (10.8)	68.1 (9.6)	70.3 (4.7)	63.7 (9.8)	54.0 (11.3)	63.2 (11.2)	64.3 (10.5)
Sex: Female, Male (Count of Participants)
Female	5 13.5%	13 18.1%	4 10%	0 0%	5 11.4%	0 0%	0 0%	27 13.2%
Male	32 86.5%	59 81.9%	36 90%	3 100%	39 88.6%	3 100%	5 100%	177 86.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	1 33.3%	0 0%	0 0%	0 0%	1 0.5%
Asian	1 2.7%	7 9.7%	1 2.5%	0 0%	6 13.6%	2 66.7%	4 80%	21 10.3%
Native Hawaiian or Other Pacific Islander	0 0%	2 2.8%	0 0%	0 0%	7 15.9%	0 0%	0 0%	9 4.4%
Black or African American	2 5.4%	3 4.2%	1 2.5%	0 0%	2 4.5%	0 0%	1 20%	9 4.4%
White	34 91.9%	58 80.6%	35 87.5%	2 66.7%	20 45.5%	0 0%	0 0%	149 73%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	2 2.8%	3 7.5%	0 0%	9 20.5%	1 33.3%	0 0%	15 7.4%
Region of Enrollment (Count of Participants)
New Zealand	2 5.4%	5 6.9%	4 10%	0 0%	12 27.3%	0 0%	0 0%	23 11.3%
United States	6 16.2%	12 16.7%	4 10%	1 33.3%	10 22.7%	3 100%	5 100%	41 20.1%
Italy	12 32.4%	15 20.8%	9 22.5%	0 0%	4 9.1%	0 0%	0 0%	40 19.6%
Australia	0 0%	3 4.2%	2 5%	0 0%	0 0%	0 0%	0 0%	5 2.5%
France	12 32.4%	27 37.5%	16 40%	0 0%	14 31.8%	0 0%	0 0%	69 33.8%
Germany	4 10.8%	7 9.7%	4 10%	2 66.7%	4 9.1%	0 0%	0 0%	21 10.3%
Spain	1 2.7%	3 4.2%	1 2.5%	0 0%	0 0%	0 0%	0 0%	5 2.5%
Alpha-Fetoprotein (Count of Participants)
< 200 nanograms per Liter (µg/L)	9 24.3%	23 31.9%	28 70%	2 66.7%	20 45.5%	1 33.3%	2 40%	85 41.7%
200 - 400 (µg/L)	3 8.1%	5 6.9%	0 0%	0 0%	4 9.1%	0 0%	0 0%	12 5.9%
> 400 (µg/L)	23 62.2%	43 59.7%	0 0%	1 33.3%	16 36.4%	2 66.7%	2 40%	87 42.6%
Unknown/Not reported	2 5.4%	1 1.4%	12 30%	0 0%	4 9.1%	0 0%	1 20%	20 9.8%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Relationship of Biomarker Alpha-fetoprotein (AFP) to Overall Survival (OS)
Description	Biomarker response was defined as a > 20% decrease in the biomarker AFP from baseline during 8 weeks of treatment. Data presented is median overall survival of those participants who achieved the defined biomarker response. Participants enrolled in Part A had a baseline AFP level of >1.5 upper limit normal (ULN). Participants enrolled in Part B had baseline AFP level <1.5 ULN.
Time Frame	Baseline, discontinuation from any cause (Up to 83 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug, achieved a >20% reduction in biomarker AFP, and had evaluable post-baseline biomarker data. Due to low enrollment into Part C Cohort - 160 mg reporting group, Kaplan Meier analysis for OS was not conducted in this subgroup. Per protocol, Part D collected safety data only.

Arm/Group Title	Part A Cohort 1 - 160 mg LY2157299	Part A Cohort 2 - 300 mg LY2157299	Part B LY2157299	Part C LY2157299
Arm/Group Description	80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle) for Cohort 1.	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
Measure Participants	8	14	10	27
Median (95% Confidence Interval) [Months]	19.0	21.5	24.2	17.9

2. Primary Outcome

Title	Change From Baseline in Relationship of Biomarker Transforming Growth Factor - Beta (TGF-β) to Overall Survival (OS)
Description	Biomarker response was defined as a > 20% decrease in the biomarker TGF-B from baseline. Data presented is median overall survival of those participants who achieved biomarker response.
Time Frame	Baseline,discontinuation from any cause (Up to 83 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug, achieved a >20% reduction in biomarker TGF-β and had evaluable post-baseline biomarker data. Due to low enrollment in Part C Cohort 1 - 160 mg reporting group, Kaplan Meier analysis for OS was not conducted in this subgroup. Per protocol, Part D collected safety data only.

Arm/Group Title	Part A Cohort 1 - 160 mg LY2157299	Part A Cohort 2 - 300 mg LY2157299	Part B LY2157299	Part C LY2157299
Arm/Group Description	80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle) for Cohort 1.	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle) for Cohort 2.	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days 0ff (28-day cycle).
Measure Participants	16	34	28	31
Median (95% Confidence Interval) [Months]	11.9	10.1	21.9	22.88

3. Primary Outcome

Title	Time to Progression (TTP)
Description	TTP is measured from the date of first dose to the first date of progression of disease based on the investigator review of tumor response using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Progression is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.
Time Frame	Randomization to date of first measured progressive disease (Up to 36 Weeks)

Outcome Measure Data

Analysis Population Description

All participants who receive at least one dose of study drug. Per protocol, Part D collected safety data only.

Arm/Group Title	Part A Cohort 1 - 160 mg LY2157299	Part A Cohort 2 - 300 mg LY2157299	Part B - 300 mg LY2157299	Part C Cohort 1 - 160 mg + Sorafenib	Part C Cohort 2 - 300 mg LY2157299 + Sorafenib
Arm/Group Description	80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	80 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib	150 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day
Measure Participants	37	72	40	3	44
Median (90% Confidence Interval) [Weeks]	12.1	7.1	18.0	36.0	17.9

4. Secondary Outcome

Title	Population Pharmacokinetics (PK) Mean Population Clearance of Galunisertib
Description	Population mean (between-subject coefficient variance [CV %]) apparent clearance.
Time Frame	Cycle (C) 1: Day (D)1: Predose, 0.5-2 hours(h) Postdose; D14: Predose, 0.5-2, 3-5 h, Postdose; D15 Morning; D22 Morning; Predose C2 and C3 Predose D1

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug, regardless of dose, with evaluable PK data. Per protocol, Part D collected safety data only.

Arm/Group Title	LY2157299
Arm/Group Description	LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
Measure Participants	143
Geometric Mean (Geometric Coefficient of Variation) [Liter per hour (L/hr)]	33.6 (48)

5. Secondary Outcome

Title	Recommended Dose for Phase 3 Hepatocellular Carcinoma (HCC) Trials
Time Frame	Cycle 1 (28 Days)

Outcome Measure Data

Analysis Population Description

All participants in Part A and Part B.

Arm/Group Title	LY2157299
Arm/Group Description	LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
Measure Participants	74
Number [milligrams (mg)]	300

6. Secondary Outcome

Title	Overall Survival (OS)
Description	OS duration is measured from the date of first dose to the date of death from any cause.
Time Frame	Randomization to date of death from any cause (Up to 83 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug. Per protocol, Part D collected safety data only.

Arm/Group Title	Part A Cohort 1 - 160 mg LY2157299	Part A Cohort 2 - 300 mg LY2157299	Part B - 300 mg LY2157299	Part C Cohort 1 - 160 mg LY2157299 + Sorafenib	Part C Cohort 2 - 300 mg LY2157299 + Sorafenib
Arm/Group Description	80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	80 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).	150 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).
Measure Participants	37	72	40	3	44
Median (90% Confidence Interval) [Weeks]	39.1	29.6	73.0	30.3	89.6

7. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS duration is measure from the date of first dose to the first date of objective progression of disease or death from any cause. Progression is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.
Time Frame	Randomization to measured progressive disease or death from any cause (Up to 45 Weeks)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug. Per protocol, Part D collected safety data only.

Arm/Group Title	Part A Cohort 1 - 160 mg LY2157299	Part A Cohort 2 - 300 mg LY2157299	Part B - 300 mg LY2157299	Part C Cohort 1 - 160 mg LY2157299 + Sorafenib	Part C Cohort 2 - 300 mg LY2157299 + Sorafenib
Arm/Group Description	80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally 150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	80 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day	150 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).
Measure Participants	37	72	40	3	44
Median (90% Confidence Interval) [Weeks]	12	6.6	13.4	28.4	28.4

8. Secondary Outcome

Title	Percentage of Participants Achieving an Objective Response (Response Rate)
Description	The percentage of participants who achieved best overall response of either Complete Response (CR) or Partial Response (PR). The overall response rate for each dose with be estimated by dividing the number of confirmed responders by the number of participants who received at least one dose of study drug. Per RECIST v.1.0 criteria CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 millimeter (mm). Tumor-marker results must have normalized. PR is defined as at least 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters.
Time Frame	Randomization to measured progressive disease (Up to 36 Weeks)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug. Per protocol, Part D collected safety data only.

Arm/Group Title	Part A Cohort 1 - 160 mg LY2157299	Part A Cohort 2 - 300 mg LY2157299	Part B - 300 mg LY2157299	Part C Cohort 1 - 160 mg LY2157299 + Sorafenib	Part C Cohort 2 - 300 mg LY2157299 + Sorafenib
Arm/Group Description	80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	80 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).	150 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).
Measure Participants	30	46	27	3	44
Complete Response	0 0%	0 0%	0 0%	0 0%	0 0%
Partial Response	0 0%	0 0%	3.7 9.3%	0 0%	2.3 5.2%

9. Secondary Outcome

Title	Duration of Tumor Response (DoR)
Description	DoR is measured from the date of the first objective status assessment of a Complete Response (CR) or Partial Response (PR), as determined by RECIST v1.1, to the first date of objective progression of disease or death from any cause. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 millimeter (mm). Tumor-marker results must have normalized. PR is defined as at least 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progression is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.
Time Frame	Time of response to measured progressive disease or death from any cause (Up to 84 Weeks)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug with assessment of CR or PR. Per protocol, Part D collected safety data only.

Arm/Group Title	Part A Cohort 1 - 160 mg LY2157299	Part A Cohort 2 - 300 mg LY2157299	Part B - 300 mg LY2157299	Part C Cohort 1 - 160 mg LY2157299 + Sorafenib	Part C Cohort 2 - 300 mg LY2157299 + Sorafenib
Arm/Group Description	80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	80 mg LY2157299 given orally BID on days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle	150 mg LY2157299 given orally BID on days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle
Measure Participants	0	0	2	0	4
Median (90% Confidence Interval) [Weeks]	37.6	40.2

10. Secondary Outcome

Title	Time to Treatment Failure (TTF)
Description	TTF is measured from the date of first dose until the date of discontinuation of study treatment due to adverse event, progression of disease, or death from any cause.
Time Frame	Randomization to the date of discontinuation of study treatment due to adverse event, progression of disease, or death from any cause (Up to 75 Weeks)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug. Per protocol, Part D collected safety data only.

Arm/Group Title	Part A Cohort 1 - 160 mg LY2157299	Part A Cohort 2 - 300 mg LY2157299	Part B - 300 mg LY2157299	Part C Cohort 1 - 160 mg LY2157299 + Sorafenib	Part C Cohort 2 - 300 mg LY2157299 + Sorafenib
Arm/Group Description	80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	80 mg LY2157299 given orally BID on days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).	150 mg LY2157299 given orally BID on days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).
Measure Participants	37	72	40	3	44
Median (90% Confidence Interval) [Weeks]	13.4	9.9	19.3	26.3	49.3

11. Secondary Outcome

Title	Change From Baseline in Functional Assessment of Cancer Therapy, Hepatobiliary (FACT-Hep) Sub-scores and Total Score
Description	FACT-Hep consists of 45 items in five subscales (1) physical well-being (PWB) score rage 0 -28; (2) social well-being (SWB) score range 0-28; (3) emotional well-being (EWB) score range 0-24; (4) functional well-being (FWB) score range 0-28; and (5) the hepatobiliary cancer subscale (HCS) Score range 0-72; FACT-Hep score range 1-180, and Trial-Outcome Index (TOI) score range 1-128, to assess health related quality of life in participants with cancer. Higher scores reflect a better health state.
Time Frame	Baseline, Day 1 Cycle 4

Outcome Measure Data

Analysis Population Description

All participants with baseline and one post-baseline FACT-Hep Questionnaire in Cycles 2, 3, or 4. Per protocol, Part D collected safety data only.

Arm/Group Title	Part A Cohort 1 - 160 mg LY2157299	Part A Cohort 2 - 300 mg LY2157299	Part B - 300 mg LY2157299	Part C Cohort 1 - 160mg LY2157299 + Sorafenib	Part C Cohort 2 - 300 mg LY2157299 + Sorafenib
Arm/Group Description	80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	80 mg LY2157299 given orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kilogram (kg) intravenous (IV) on days 1 and 15 (28-day cycle).	150 mg LY2157299 given orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kilogram (kg) intravenous (IV) on days 1 and 15 (28-day cycle).
Measure Participants	30	51	38	3	39
PWB	0.06 (3.6)	-0.16 (5.0)	0.04 (3.4)	-1.67 (1.5)	-1.75 (4.4)
SWB	0.96 (2.9)	0.24 (3.4)	0.37 (4.5)	-1.11 (2.8)	0.41 (3.6)
EWB	0.55 (2.7)	1.17 (3.9)	1.13 (4.1)	2.87 (2.8)	0.85 (2.5)
FWB	-0.02 (5.3)	0.84 (3.6)	1.20 (4.7)	-1.00 (1.0)	-1.19 (4.6)
HCS	1.93 (7.6)	1.40 (7.8)	0.89 (6.8)	1.08 (6.0)	-3.79 (7.3)
FACT-Hep	2.04 (1.53)	1.50 (17.5)	0.58 (18.2)	-0.50 (6.5)	-8.54 (17.0)
TOI	1.34 (13.3)	1.14 (14.6)	1.17 (12.2)	-1.92 (7.7)	-8.28 (13.7)

12. Secondary Outcome

Title	Time to Worsening (TTW) of Symptoms (FACT-Hep)
Description	Time to worsening of symptoms used minimally important differences to evaluate Physical Well Being (PWB), Functional Well Being (FWB), Hepatocellular Cancer Symptoms (HCS), National Comprehensive Cancer Network (NCCN)/FACT Hepatocellular Symptoms (FHS), Trial-Outcome Index (TOI). PWB time to worsening was defined as participants who had change in a subscale of ≥ 2 point decrease from baseline; FWB time to worsening was defined as participants who had change in a subscale of ≥ 2 point decrease from baseline; HCS time to worsening was defined as participants who had change in a subscale of ≥ 5 point decrease from baseline; FHS time to worsening was defined as participants who had change in a subscale of ≥ 2 point decrease from baseline; TOI time to Worsening was defined as participants who had change in the subscale of ≥ 7 point decrease from baseline.
Time Frame	Baseline to the worsening of symptoms (up to 567 days)

Outcome Measure Data

Analysis Population Description

All participants who completed a baseline and one post-baseline FACT-Hep TTW questionnaire. Due to low enrollment in Part C Cohort 1 - 160 mg reporting group, time-to-event analysis for TTW was not conducted for this subgroup. Per protocol, Part D collected safety data only.

Arm/Group Title	Part A Cohort 1 - 160 mg LY2157299	Part A Cohort 2 - 300 mg LY2157299	Part B - 300 mg LY2157299	Part C Cohort 2 - 300mg LY2157299
Arm/Group Description	80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).	150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
Measure Participants	30	61	37	40
PWB	114.0	113.0	113.0	30.0
FWB	57.0	88.0	64.0	30.0
HCS	114.0	113.0	170.0	31.0
FHS	55.0	57.0	57.0	30.0
TOI	114.0	113.0	179.0	30.0

Adverse Events

Time Frame	Baseline up to 41.5 months
Adverse Event Reporting Description	All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
Arm/Group Title	Part A Cohort 1 - 160 mg LY2157299		Part A Cohort 2 - 300 mg LY2157299		Part B - 300 mg LY2157299		Part C Cohort 1 - 160 mg LY2157299 + Sorafenib		Part C Cohort 2 - 300 mg LY2157299 + Sorafenib		Part D Cohort 1 - 160 mg LY2157299 + Ramucirumab		Part D Cohort 2 - 300 mg LY2157299 + Ramucirumab
Arm/Group Description	80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).		150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).		150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).		80 mg LY2157299 given orally BID on days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).		150 mg LY2157299 given orally BID on days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).		80 mg LY2157299 given orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kg IV on days 1 and 15 (28-day cycle).		150 mg LY2157299 given orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kg IV on days 1 and 15 (28-day cycle).
All Cause Mortality
	Part A Cohort 1 - 160 mg LY2157299		Part A Cohort 2 - 300 mg LY2157299		Part B - 300 mg LY2157299		Part C Cohort 1 - 160 mg LY2157299 + Sorafenib		Part C Cohort 2 - 300 mg LY2157299 + Sorafenib		Part D Cohort 1 - 160 mg LY2157299 + Ramucirumab		Part D Cohort 2 - 300 mg LY2157299 + Ramucirumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/37 (89.2%)		63/72 (87.5%)		26/40 (65%)		3/3 (100%)		36/44 (81.8%)		2/3 (66.7%)		5/5 (100%)
Serious Adverse Events
	Part A Cohort 1 - 160 mg LY2157299		Part A Cohort 2 - 300 mg LY2157299		Part B - 300 mg LY2157299		Part C Cohort 1 - 160 mg LY2157299 + Sorafenib		Part C Cohort 2 - 300 mg LY2157299 + Sorafenib		Part D Cohort 1 - 160 mg LY2157299 + Ramucirumab		Part D Cohort 2 - 300 mg LY2157299 + Ramucirumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/37 (40.5%)		36/72 (50%)		16/40 (40%)		3/3 (100%)		28/44 (63.6%)		1/3 (33.3%)		2/5 (40%)
Blood and lymphatic system disorders
Anaemia	2/37 (5.4%)	2	7/72 (9.7%)	16	3/40 (7.5%)	5	1/3 (33.3%)	2	6/44 (13.6%)	9	0/3 (0%)	0	0/5 (0%)	0
Neutropenia	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Thrombocytopenia	0/37 (0%)	0	0/72 (0%)	0	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Cardiac disorders
Acute coronary syndrome	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Acute myocardial infarction	1/37 (2.7%)	1	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Angina unstable	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Atrial fibrillation	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Atrial thrombosis	0/37 (0%)	0	0/72 (0%)	0	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Cardiac failure	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Left ventricular dysfunction	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Left ventricular failure	1/37 (2.7%)	1	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Gastrointestinal disorders
Abdominal distension	0/37 (0%)	0	1/72 (1.4%)	2	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Abdominal pain	0/37 (0%)	0	3/72 (4.2%)	3	1/40 (2.5%)	1	0/3 (0%)	0	1/44 (2.3%)	2	0/3 (0%)	0	0/5 (0%)	0
Abdominal pain upper	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Ascites	2/37 (5.4%)	2	4/72 (5.6%)	6	1/40 (2.5%)	1	0/3 (0%)	0	2/44 (4.5%)	2	0/3 (0%)	0	0/5 (0%)	0
Diarrhoea	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Duodenal ulcer	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	1/3 (33.3%)	1	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Gastric ulcer	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Gastric varices haemorrhage	0/37 (0%)	0	1/72 (1.4%)	1	1/40 (2.5%)	2	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Gastrointestinal haemorrhage	0/37 (0%)	0	1/72 (1.4%)	2	1/40 (2.5%)	1	1/3 (33.3%)	1	0/44 (0%)	0	0/3 (0%)	0	1/5 (20%)	1
Haematemesis	0/37 (0%)	0	0/72 (0%)	0	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Intestinal obstruction	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Intra-abdominal haemorrhage	1/37 (2.7%)	1	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Large intestinal haemorrhage	1/37 (2.7%)	1	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Lower gastrointestinal haemorrhage	1/37 (2.7%)	1	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Melaena	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Nausea	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Oesophageal varices haemorrhage	1/37 (2.7%)	1	1/72 (1.4%)	1	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Pancreatitis	1/37 (2.7%)	1	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Peritoneal haematoma	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Peritoneal haemorrhage	0/37 (0%)	0	1/72 (1.4%)	1	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Rectal haemorrhage	0/37 (0%)	0	1/72 (1.4%)	3	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Small intestinal haemorrhage	0/37 (0%)	0	1/72 (1.4%)	2	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Subileus	1/37 (2.7%)	1	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Upper gastrointestinal haemorrhage	0/37 (0%)	0	1/72 (1.4%)	1	2/40 (5%)	4	1/3 (33.3%)	1	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Varices oesophageal	0/37 (0%)	0	1/72 (1.4%)	1	2/40 (5%)	3	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Vomiting	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
General disorders
Asthenia	1/37 (2.7%)	1	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Chest discomfort	1/37 (2.7%)	1	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
General physical health deterioration	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	1/3 (33.3%)	1	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Pain	1/37 (2.7%)	1	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Pyrexia	1/37 (2.7%)	1	2/72 (2.8%)	2	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Hepatobiliary disorders
Acute hepatic failure	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	1/5 (20%)	1
Gallbladder rupture	0/37 (0%)	0	0/72 (0%)	0	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Hepatic failure	1/37 (2.7%)	1	2/72 (2.8%)	2	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Hepatic haematoma	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Hepatic haemorrhage	1/37 (2.7%)	1	2/72 (2.8%)	2	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Hepatic pain	0/37 (0%)	0	2/72 (2.8%)	2	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Hepatorenal syndrome	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Hyperbilirubinaemia	1/37 (2.7%)	1	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Jaundice cholestatic	1/37 (2.7%)	1	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Portal vein thrombosis	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Infections and infestations
Anal abscess	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Arthritis bacterial	0/37 (0%)	0	0/72 (0%)	0	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Cellulitis	1/37 (2.7%)	1	0/72 (0%)	0	1/40 (2.5%)	2	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Diverticulitis	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Endocarditis	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Liver abscess	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	2/44 (4.5%)	2	0/3 (0%)	0	0/5 (0%)	0
Lower respiratory tract infection	1/37 (2.7%)	1	0/72 (0%)	0	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Lung infection	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	2	0/3 (0%)	0	0/5 (0%)	0
Osteomyelitis	0/37 (0%)	0	0/72 (0%)	0	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Peritonitis bacterial	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Pneumonia	0/37 (0%)	0	4/72 (5.6%)	4	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	2	0/3 (0%)	0	0/5 (0%)	0
Sepsis	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	2/44 (4.5%)	2	0/3 (0%)	0	0/5 (0%)	0
Urinary tract infection	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Wound infection	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Injury, poisoning and procedural complications
Cervical vertebral fracture	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Concussion	0/37 (0%)	0	0/72 (0%)	0	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Exposure during pregnancy	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Femur fracture	1/37 (2.7%)	1	1/72 (1.4%)	1	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Pelvic fracture	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Post procedural haemorrhage	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Radiation pneumonitis	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Shunt stenosis	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Toxicity to various agents	0/37 (0%)	0	1/72 (1.4%)	1	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Investigations
Blood bilirubin increased	1/37 (2.7%)	1	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Liver function test abnormal	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/37 (2.7%)	1	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Dehydration	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Fluid retention	1/37 (2.7%)	1	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Hyperammonaemia	1/37 (2.7%)	1	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Hyperglycaemia	1/37 (2.7%)	1	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/37 (0%)	0	2/72 (2.8%)	2	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Chondrocalcinosis pyrophosphate	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Joint effusion	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Musculoskeletal pain	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Myalgia	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Osteoarthritis	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant ascites	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Malignant neoplasm progression	0/37 (0%)	0	0/72 (0%)	0	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Neoplasm progression	1/37 (2.7%)	1	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Pancreatic neuroendocrine tumour	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	1/5 (20%)	1
Second primary malignancy	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	1/3 (33.3%)	1	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Squamous cell carcinoma	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Squamous cell carcinoma of lung	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Squamous cell carcinoma of skin	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Tumour haemorrhage	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Tumour pain	2/37 (5.4%)	3	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Nervous system disorders
Cerebrovascular accident	0/37 (0%)	0	0/72 (0%)	0	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Embolic stroke	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	1/3 (33.3%)	1	0/5 (0%)	0
Encephalopathy	1/37 (2.7%)	1	2/72 (2.8%)	2	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Haemorrhage intracranial	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Hepatic encephalopathy	2/37 (5.4%)	3	1/72 (1.4%)	1	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	1/5 (20%)	1
Loss of consciousness	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Presyncope	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Transient ischaemic attack	0/37 (0%)	0	0/72 (0%)	0	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Psychiatric disorders
Confusional state	1/37 (2.7%)	2	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Disorientation	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Renal and urinary disorders
Acute kidney injury	1/37 (2.7%)	1	2/72 (2.8%)	2	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Haematuria	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	2	0/3 (0%)	0	0/5 (0%)	0
Prerenal failure	1/37 (2.7%)	1	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Renal disorder	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Renal impairment	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Renal injury	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	1/3 (33.3%)	1	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Urinary retention	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/37 (0%)	0	1/72 (1.4%)	1	1/40 (2.5%)	3	0/3 (0%)	0	2/44 (4.5%)	2	0/3 (0%)	0	0/5 (0%)	0
Pleural effusion	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Pneumonia aspiration	0/37 (0%)	0	0/72 (0%)	0	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Pneumonitis	0/37 (0%)	0	0/72 (0%)	0	1/40 (2.5%)	1	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Pulmonary embolism	1/37 (2.7%)	1	0/72 (0%)	0	2/40 (5%)	2	1/3 (33.3%)	1	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Pulmonary infarction	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Pulmonary oedema	1/37 (2.7%)	1	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Respiratory failure	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Skin and subcutaneous tissue disorders
Drug eruption	0/37 (0%)	0	0/72 (0%)	0	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Vascular disorders
Dry gangrene	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Shock haemorrhagic	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Thrombosis	1/37 (2.7%)	1	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Other (Not Including Serious) Adverse Events
	Part A Cohort 1 - 160 mg LY2157299		Part A Cohort 2 - 300 mg LY2157299		Part B - 300 mg LY2157299		Part C Cohort 1 - 160 mg LY2157299 + Sorafenib		Part C Cohort 2 - 300 mg LY2157299 + Sorafenib		Part D Cohort 1 - 160 mg LY2157299 + Ramucirumab		Part D Cohort 2 - 300 mg LY2157299 + Ramucirumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/37 (86.5%)		64/72 (88.9%)		38/40 (95%)		3/3 (100%)		44/44 (100%)		3/3 (100%)		5/5 (100%)
Blood and lymphatic system disorders
Anaemia	9/37 (24.3%)	22	13/72 (18.1%)	23	10/40 (25%)	20	1/3 (33.3%)	4	12/44 (27.3%)	17	0/3 (0%)	0	0/5 (0%)	0
Neutropenia	3/37 (8.1%)	9	3/72 (4.2%)	4	1/40 (2.5%)	1	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Thrombocytopenia	2/37 (5.4%)	2	2/72 (2.8%)	2	3/40 (7.5%)	9	0/3 (0%)	0	7/44 (15.9%)	22	0/3 (0%)	0	0/5 (0%)	0
Ear and labyrinth disorders
Tinnitus	0/37 (0%)	0	0/72 (0%)	0	3/40 (7.5%)	3	0/3 (0%)	0	2/44 (4.5%)	2	0/3 (0%)	0	0/5 (0%)	0
Vertigo	0/37 (0%)	0	1/72 (1.4%)	1	1/40 (2.5%)	1	1/3 (33.3%)	1	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Gastrointestinal disorders
Abdominal distension	2/37 (5.4%)	3	2/72 (2.8%)	2	5/40 (12.5%)	5	0/3 (0%)	0	4/44 (9.1%)	4	1/3 (33.3%)	1	2/5 (40%)	2
Abdominal pain	7/37 (18.9%)	7	11/72 (15.3%)	12	8/40 (20%)	10	1/3 (33.3%)	1	7/44 (15.9%)	8	0/3 (0%)	0	2/5 (40%)	2
Abdominal pain upper	1/37 (2.7%)	1	7/72 (9.7%)	10	4/40 (10%)	4	0/3 (0%)	0	4/44 (9.1%)	5	0/3 (0%)	0	1/5 (20%)	1
Ascites	5/37 (13.5%)	7	8/72 (11.1%)	8	2/40 (5%)	3	0/3 (0%)	0	6/44 (13.6%)	8	0/3 (0%)	0	0/5 (0%)	0
Barrett's oesophagus	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	1/3 (33.3%)	1	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Constipation	5/37 (13.5%)	6	11/72 (15.3%)	14	7/40 (17.5%)	7	0/3 (0%)	0	6/44 (13.6%)	8	0/3 (0%)	0	1/5 (20%)	1
Diarrhoea	5/37 (13.5%)	8	10/72 (13.9%)	13	11/40 (27.5%)	15	1/3 (33.3%)	2	21/44 (47.7%)	43	1/3 (33.3%)	1	1/5 (20%)	1
Dry mouth	1/37 (2.7%)	1	4/72 (5.6%)	4	2/40 (5%)	2	1/3 (33.3%)	1	2/44 (4.5%)	2	1/3 (33.3%)	1	0/5 (0%)	0
Flatulence	2/37 (5.4%)	3	0/72 (0%)	0	1/40 (2.5%)	1	2/3 (66.7%)	2	3/44 (6.8%)	3	0/3 (0%)	0	0/5 (0%)	0
Gingival bleeding	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	1/3 (33.3%)	1	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Nausea	6/37 (16.2%)	11	15/72 (20.8%)	21	9/40 (22.5%)	9	1/3 (33.3%)	2	12/44 (27.3%)	17	1/3 (33.3%)	1	1/5 (20%)	1
Portal hypertensive gastropathy	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	1/3 (33.3%)	1	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Stomatitis	1/37 (2.7%)	1	3/72 (4.2%)	3	0/40 (0%)	0	0/3 (0%)	0	5/44 (11.4%)	8	0/3 (0%)	0	0/5 (0%)	0
Varices oesophageal	0/37 (0%)	0	2/72 (2.8%)	2	1/40 (2.5%)	1	1/3 (33.3%)	1	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Vomiting	6/37 (16.2%)	6	12/72 (16.7%)	17	6/40 (15%)	11	1/3 (33.3%)	1	5/44 (11.4%)	11	0/3 (0%)	0	0/5 (0%)	0
General disorders
Asthenia	5/37 (13.5%)	6	6/72 (8.3%)	6	4/40 (10%)	8	0/3 (0%)	0	6/44 (13.6%)	14	0/3 (0%)	0	0/5 (0%)	0
Chills	3/37 (8.1%)	3	2/72 (2.8%)	3	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	1/5 (20%)	1
Fatigue	9/37 (24.3%)	10	14/72 (19.4%)	17	14/40 (35%)	15	2/3 (66.7%)	2	11/44 (25%)	16	0/3 (0%)	0	2/5 (40%)	4
Influenza like illness	1/37 (2.7%)	1	1/72 (1.4%)	1	4/40 (10%)	4	0/3 (0%)	0	3/44 (6.8%)	3	0/3 (0%)	0	0/5 (0%)	0
Localised oedema	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	1/3 (33.3%)	1	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Non-cardiac chest pain	0/37 (0%)	0	2/72 (2.8%)	2	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	1/5 (20%)	1
Oedema peripheral	5/37 (13.5%)	6	14/72 (19.4%)	16	12/40 (30%)	17	0/3 (0%)	0	10/44 (22.7%)	12	1/3 (33.3%)	1	1/5 (20%)	1
Pain	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	1/5 (20%)	1
Pyrexia	2/37 (5.4%)	4	6/72 (8.3%)	8	2/40 (5%)	2	1/3 (33.3%)	1	5/44 (11.4%)	13	0/3 (0%)	0	1/5 (20%)	1
Hepatobiliary disorders
Hyperbilirubinaemia	3/37 (8.1%)	5	3/72 (4.2%)	3	1/40 (2.5%)	1	0/3 (0%)	0	4/44 (9.1%)	5	0/3 (0%)	0	0/5 (0%)	0
Portal vein thrombosis	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	1/5 (20%)	1
Infections and infestations
Bronchitis	0/37 (0%)	0	3/72 (4.2%)	3	4/40 (10%)	4	0/3 (0%)	0	2/44 (4.5%)	2	0/3 (0%)	0	0/5 (0%)	0
Furuncle	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	3/44 (6.8%)	3	0/3 (0%)	0	0/5 (0%)	0
Lung infection	0/37 (0%)	0	0/72 (0%)	0	1/40 (2.5%)	1	0/3 (0%)	0	3/44 (6.8%)	7	0/3 (0%)	0	0/5 (0%)	0
Post abortion infection	0/5 (0%)	0	0/13 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	1/5 (20%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Upper respiratory tract infection	1/37 (2.7%)	1	1/72 (1.4%)	1	1/40 (2.5%)	1	0/3 (0%)	0	2/44 (4.5%)	3	1/3 (33.3%)	1	0/5 (0%)	0
Urinary tract infection	0/37 (0%)	0	2/72 (2.8%)	2	1/40 (2.5%)	2	1/3 (33.3%)	1	5/44 (11.4%)	5	0/3 (0%)	0	0/5 (0%)	0
Vaginal infection	0/5 (0%)	0	0/13 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	1/5 (20%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Viral infection	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	1/3 (33.3%)	1	0/5 (0%)	0
Vulvovaginal candidiasis	0/5 (0%)	0	0/13 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	1/5 (20%)	1	0/0 (NaN)	0	0/0 (NaN)	0
Injury, poisoning and procedural complications
Fall	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	1/3 (33.3%)	1	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Investigations
Aspartate aminotransferase increased	2/37 (5.4%)	3	3/72 (4.2%)	3	2/40 (5%)	2	1/3 (33.3%)	1	3/44 (6.8%)	3	0/3 (0%)	0	0/5 (0%)	0
Blood alkaline phosphatase increased	0/37 (0%)	0	1/72 (1.4%)	1	1/40 (2.5%)	1	1/3 (33.3%)	1	2/44 (4.5%)	2	0/3 (0%)	0	0/5 (0%)	0
Blood bilirubin increased	1/37 (2.7%)	1	3/72 (4.2%)	3	2/40 (5%)	2	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	1/5 (20%)	1
Haemoglobin decreased	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	1/3 (33.3%)	1	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Weight decreased	4/37 (10.8%)	5	8/72 (11.1%)	8	10/40 (25%)	17	3/3 (100%)	7	24/44 (54.5%)	58	0/3 (0%)	0	0/5 (0%)	0
Weight increased	1/37 (2.7%)	1	7/72 (9.7%)	8	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	6/37 (16.2%)	7	7/72 (9.7%)	8	7/40 (17.5%)	7	2/3 (66.7%)	2	10/44 (22.7%)	15	0/3 (0%)	0	0/5 (0%)	0
Hypercalcaemia	3/37 (8.1%)	4	1/72 (1.4%)	2	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Hypoalbuminaemia	0/37 (0%)	0	3/72 (4.2%)	4	2/40 (5%)	3	0/3 (0%)	0	3/44 (6.8%)	3	0/3 (0%)	0	0/5 (0%)	0
Hypokalaemia	0/37 (0%)	0	1/72 (1.4%)	1	1/40 (2.5%)	1	0/3 (0%)	0	4/44 (9.1%)	6	0/3 (0%)	0	0/5 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	3/37 (8.1%)	5	3/72 (4.2%)	3	5/40 (12.5%)	5	0/3 (0%)	0	6/44 (13.6%)	6	0/3 (0%)	0	0/5 (0%)	0
Back pain	2/37 (5.4%)	3	5/72 (6.9%)	9	1/40 (2.5%)	2	0/3 (0%)	0	3/44 (6.8%)	3	0/3 (0%)	0	0/5 (0%)	0
Muscle spasms	2/37 (5.4%)	2	2/72 (2.8%)	3	5/40 (12.5%)	7	0/3 (0%)	0	6/44 (13.6%)	7	0/3 (0%)	0	0/5 (0%)	0
Muscular weakness	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	1/3 (33.3%)	1	0/5 (0%)	0
Musculoskeletal chest pain	0/37 (0%)	0	2/72 (2.8%)	3	1/40 (2.5%)	1	0/3 (0%)	0	1/44 (2.3%)	1	2/3 (66.7%)	2	0/5 (0%)	0
Myalgia	1/37 (2.7%)	1	1/72 (1.4%)	1	1/40 (2.5%)	1	0/3 (0%)	0	10/44 (22.7%)	11	0/3 (0%)	0	0/5 (0%)	0
Pain in extremity	1/37 (2.7%)	1	3/72 (4.2%)	3	1/40 (2.5%)	2	0/3 (0%)	0	3/44 (6.8%)	6	0/3 (0%)	0	0/5 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/37 (0%)	0	0/72 (0%)	0	1/40 (2.5%)	1	1/3 (33.3%)	1	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Malignant ascites	1/37 (2.7%)	1	5/72 (6.9%)	5	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Tumour pain	4/37 (10.8%)	4	1/72 (1.4%)	1	1/40 (2.5%)	1	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Nervous system disorders
Embolic stroke	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	1/3 (33.3%)	1	0/5 (0%)	0
Headache	1/37 (2.7%)	1	4/72 (5.6%)	4	5/40 (12.5%)	5	0/3 (0%)	0	3/44 (6.8%)	3	0/3 (0%)	0	1/5 (20%)	1
Hepatic encephalopathy	2/37 (5.4%)	2	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Peripheral sensory neuropathy	3/37 (8.1%)	3	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Somnolence	2/37 (5.4%)	2	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Taste disorder	1/37 (2.7%)	1	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	1/5 (20%)	1
Psychiatric disorders
Anxiety	1/37 (2.7%)	1	4/72 (5.6%)	4	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Confusional state	2/37 (5.4%)	2	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	1/5 (20%)	1
Insomnia	2/37 (5.4%)	2	5/72 (6.9%)	6	4/40 (10%)	4	0/3 (0%)	0	5/44 (11.4%)	5	0/3 (0%)	0	0/5 (0%)	0
Renal and urinary disorders
Haematuria	1/37 (2.7%)	1	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	3/44 (6.8%)	3	0/3 (0%)	0	0/5 (0%)	0
Nocturia	0/37 (0%)	0	2/72 (2.8%)	2	0/40 (0%)	0	0/3 (0%)	0	0/44 (0%)	0	0/3 (0%)	0	1/5 (20%)	1
Reproductive system and breast disorders
Erectile dysfunction	1/32 (3.1%)	1	0/59 (0%)	0	0/36 (0%)	0	0/3 (0%)	0	2/39 (5.1%)	2	0/3 (0%)	0	0/5 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	3/37 (8.1%)	3	5/72 (6.9%)	5	3/40 (7.5%)	4	0/3 (0%)	0	3/44 (6.8%)	4	0/3 (0%)	0	1/5 (20%)	1
Dyspnoea	3/37 (8.1%)	3	9/72 (12.5%)	10	6/40 (15%)	7	0/3 (0%)	0	5/44 (11.4%)	5	1/3 (33.3%)	1	1/5 (20%)	2
Epistaxis	1/37 (2.7%)	3	2/72 (2.8%)	2	3/40 (7.5%)	3	0/3 (0%)	0	4/44 (9.1%)	5	3/3 (100%)	3	1/5 (20%)	1
Oropharyngeal pain	1/37 (2.7%)	1	1/72 (1.4%)	1	1/40 (2.5%)	1	0/3 (0%)	0	1/44 (2.3%)	1	0/3 (0%)	0	1/5 (20%)	1
Skin and subcutaneous tissue disorders
Alopecia	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	0/3 (0%)	0	9/44 (20.5%)	9	0/3 (0%)	0	0/5 (0%)	0
Dry skin	1/37 (2.7%)	1	3/72 (4.2%)	3	1/40 (2.5%)	1	0/3 (0%)	0	7/44 (15.9%)	7	0/3 (0%)	0	0/5 (0%)	0
Erythema multiforme	0/37 (0%)	0	1/72 (1.4%)	1	1/40 (2.5%)	1	1/3 (33.3%)	1	1/44 (2.3%)	1	0/3 (0%)	0	0/5 (0%)	0
Night sweats	2/37 (5.4%)	2	0/72 (0%)	0	0/40 (0%)	0	1/3 (33.3%)	1	0/44 (0%)	0	0/3 (0%)	0	0/5 (0%)	0
Palmar-plantar erythrodysaesthesia syndrome	0/37 (0%)	0	1/72 (1.4%)	1	1/40 (2.5%)	1	1/3 (33.3%)	3	28/44 (63.6%)	61	0/3 (0%)	0	0/5 (0%)	0
Pruritus	7/37 (18.9%)	9	9/72 (12.5%)	10	8/40 (20%)	10	1/3 (33.3%)	1	12/44 (27.3%)	16	0/3 (0%)	0	0/5 (0%)	0
Rash	0/37 (0%)	0	1/72 (1.4%)	1	0/40 (0%)	0	1/3 (33.3%)	3	10/44 (22.7%)	11	0/3 (0%)	0	0/5 (0%)	0
Rash maculo-papular	3/37 (8.1%)	3	1/72 (1.4%)	1	2/40 (5%)	2	1/3 (33.3%)	1	1/44 (2.3%)	2	0/3 (0%)	0	0/5 (0%)	0
Skin exfoliation	0/37 (0%)	0	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	3/44 (6.8%)	3	0/3 (0%)	0	0/5 (0%)	0
Skin lesion	1/37 (2.7%)	1	0/72 (0%)	0	0/40 (0%)	0	0/3 (0%)	0	3/44 (6.8%)	3	0/3 (0%)	0	0/5 (0%)	0
Vascular disorders
Flushing	0/37 (0%)	0	2/72 (2.8%)	3	0/40 (0%)	0	0/3 (0%)	0	3/44 (6.8%)	3	0/3 (0%)	0	0/5 (0%)	0
Haematoma	0/37 (0%)	0	1/72 (1.4%)	1	1/40 (2.5%)	1	0/3 (0%)	0	4/44 (9.1%)	4	0/3 (0%)	0	0/5 (0%)	0
Hypertension	0/37 (0%)	0	1/72 (1.4%)	1	2/40 (5%)	2	0/3 (0%)	0	8/44 (18.2%)	10	0/3 (0%)	0	0/5 (0%)	0

Limitations/Caveats

Per the protocol, following an interim analysis, the decision was taken to no longer randomize participants to the 160 mg LY2157299 arm. Per protocol, Part D collected safety data only.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.