A Study of LY2157299 in Participants With Hepatocellular Carcinoma

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

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 DiseaseIntervention/TreatmentPhase
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

ArmIntervention/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

    SiteCityStateCountryPostal Code
    1Highlands Oncology GroupFayettevilleArkansasUnited States72703
    2University of California, San FranciscoSan FranciscoCaliforniaUnited States94158
    3Georgetown University Medical CenterWashingtonDistrict of ColumbiaUnited States20007
    4MD Anderson Cancer Center OrlandoOrlandoFloridaUnited States32806
    5Northwestern UniversityChicagoIllinoisUnited States60611
    6Indiana Univ Melvin & Bren Simon Cancer CenterIndianapolisIndianaUnited States46202
    7Lahey Clinic Medical CenterBurlingtonMassachusettsUnited States01805
    8Weill Cornell Medical CollegeNew YorkNew YorkUnited States10021
    9Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUnited States10065
    10Thomas Jefferson UniversityPhiladelphiaPennsylvaniaUnited States19107
    11For 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.NedlandsWestern AustraliaAustralia6009
    12For 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.GreenslopesAustralia4120
    13For 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 physicianHeidelbergAustralia3084
    14For 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. LeonardsAustralia2065
    15For 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.BrestFrance29609
    16For 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.CaenFrance14033
    17For 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.ClichyFrance92110
    18For 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.CreteilFrance94010
    19For 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.LilleFrance59037
    20For 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.LyonFrance69317
    21For 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.MarseilleFrance13273
    22For 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.MontpellierFrance34295
    23For 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.ParisFrance75012
    24For 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.PessacFrance33604
    25For 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 physicianSaint EtienneFrance42055
    26For 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 HerblainFrance44805
    27For 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.StrasbourgFrance67085
    28For 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 NancyFrance54511
    29For 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.BerlinGermany13353
    30For 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.ErlangenGermany91054
    31For 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.GöttingenGermany37075
    32For 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.KölnGermany50937
    33For 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.MainzGermany55131
    34For 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.MünsterGermany48149
    35For 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.BariItaly70124
    36For 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.RomeItaly00168
    37For 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.RozzanoItaly20089
    38For 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.AucklandNew Zealand1023
    39For 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.BarcelonaSpain08035
    40For 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.MadridSpain28007

    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)

    More Information

    Additional Information:

    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:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment DetailParticipants 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 TitlePart A Cohort 1 - 160 mg LY2157299Part A Cohort 2 - 300 mg LY2157299Part B - 300 mg LY2157299Part C Cohort 1 - 160 mg LY2157299 + SorafenibPart C Cohort 2 - 300 mg LY2157299 + SorafenibPart D Cohort 1 - 160 mg LY2157299 + RamucirumabPart D Cohort 2 - 300 mg LY2157299 + Ramucirumab
    Arm/Group Description80 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
    STARTED37724034435
    Received at Least 1 Dose of Study Drug37724034435
    COMPLETED34673434025
    NOT COMPLETED3560410

    Baseline Characteristics

    Arm/Group TitlePart A Cohort 1 - 160 mg LY2157299Part A Cohort 2 - 300 mg LY2157299Part B - 300 mg LY2157299Part C Cohort 1 - 160 mg LY2157299 + SorafenibPart C Cohort 2 - 300 mg LY2157299 + SorafenibPart D Cohort 1 - 160 mg LY2157299 + RamucirumabPart D Cohort 2 - 300 mg LY2157299 + RamucirumabTotal
    Arm/Group Description80 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 Participants37724034435204
    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
    TitleChange From Baseline in Relationship of Biomarker Alpha-fetoprotein (AFP) to Overall Survival (OS)
    DescriptionBiomarker 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 FrameBaseline, 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 TitlePart A Cohort 1 - 160 mg LY2157299Part A Cohort 2 - 300 mg LY2157299Part B LY2157299Part C LY2157299
    Arm/Group Description80 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 Participants8141027
    Median (95% Confidence Interval) [Months]
    19.0
    21.5
    24.2
    17.9
    2. Primary Outcome
    TitleChange From Baseline in Relationship of Biomarker Transforming Growth Factor - Beta (TGF-β) to Overall Survival (OS)
    DescriptionBiomarker 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 FrameBaseline,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 TitlePart A Cohort 1 - 160 mg LY2157299Part A Cohort 2 - 300 mg LY2157299Part B LY2157299Part C LY2157299
    Arm/Group Description80 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 Participants16342831
    Median (95% Confidence Interval) [Months]
    11.9
    10.1
    21.9
    22.88
    3. Primary Outcome
    TitleTime to Progression (TTP)
    DescriptionTTP 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 FrameRandomization 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 TitlePart A Cohort 1 - 160 mg LY2157299Part A Cohort 2 - 300 mg LY2157299Part B - 300 mg LY2157299Part C Cohort 1 - 160 mg + SorafenibPart C Cohort 2 - 300 mg LY2157299 + Sorafenib
    Arm/Group Description80 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 Sorafenib150 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 Participants377240344
    Median (90% Confidence Interval) [Weeks]
    12.1
    7.1
    18.0
    36.0
    17.9
    4. Secondary Outcome
    TitlePopulation Pharmacokinetics (PK) Mean Population Clearance of Galunisertib
    DescriptionPopulation mean (between-subject coefficient variance [CV %]) apparent clearance.
    Time FrameCycle (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 TitleLY2157299
    Arm/Group DescriptionLY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
    Measure Participants143
    Geometric Mean (Geometric Coefficient of Variation) [Liter per hour (L/hr)]
    33.6
    (48)
    5. Secondary Outcome
    TitleRecommended Dose for Phase 3 Hepatocellular Carcinoma (HCC) Trials
    Description
    Time FrameCycle 1 (28 Days)

    Outcome Measure Data

    Analysis Population Description
    All participants in Part A and Part B.
    Arm/Group TitleLY2157299
    Arm/Group DescriptionLY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
    Measure Participants74
    Number [milligrams (mg)]
    300
    6. Secondary Outcome
    TitleOverall Survival (OS)
    DescriptionOS duration is measured from the date of first dose to the date of death from any cause.
    Time FrameRandomization 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 TitlePart A Cohort 1 - 160 mg LY2157299Part A Cohort 2 - 300 mg LY2157299Part B - 300 mg LY2157299Part C Cohort 1 - 160 mg LY2157299 + SorafenibPart C Cohort 2 - 300 mg LY2157299 + Sorafenib
    Arm/Group Description80 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 Participants377240344
    Median (90% Confidence Interval) [Weeks]
    39.1
    29.6
    73.0
    30.3
    89.6
    7. Secondary Outcome
    TitleProgression Free Survival (PFS)
    DescriptionPFS 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 FrameRandomization 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 TitlePart A Cohort 1 - 160 mg LY2157299Part A Cohort 2 - 300 mg LY2157299Part B - 300 mg LY2157299Part C Cohort 1 - 160 mg LY2157299 + SorafenibPart C Cohort 2 - 300 mg LY2157299 + Sorafenib
    Arm/Group Description80 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-day150 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 Participants377240344
    Median (90% Confidence Interval) [Weeks]
    12
    6.6
    13.4
    28.4
    28.4
    8. Secondary Outcome
    TitlePercentage of Participants Achieving an Objective Response (Response Rate)
    DescriptionThe 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 FrameRandomization 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 TitlePart A Cohort 1 - 160 mg LY2157299Part A Cohort 2 - 300 mg LY2157299Part B - 300 mg LY2157299Part C Cohort 1 - 160 mg LY2157299 + SorafenibPart C Cohort 2 - 300 mg LY2157299 + Sorafenib
    Arm/Group Description80 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 Participants304627344
    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
    TitleDuration of Tumor Response (DoR)
    DescriptionDoR 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 FrameTime 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 TitlePart A Cohort 1 - 160 mg LY2157299Part A Cohort 2 - 300 mg LY2157299Part B - 300 mg LY2157299Part C Cohort 1 - 160 mg LY2157299 + SorafenibPart C Cohort 2 - 300 mg LY2157299 + Sorafenib
    Arm/Group Description80 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 cycle150 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 Participants00204
    Median (90% Confidence Interval) [Weeks]
    37.6
    40.2
    10. Secondary Outcome
    TitleTime to Treatment Failure (TTF)
    DescriptionTTF 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 FrameRandomization 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 TitlePart A Cohort 1 - 160 mg LY2157299Part A Cohort 2 - 300 mg LY2157299Part B - 300 mg LY2157299Part C Cohort 1 - 160 mg LY2157299 + SorafenibPart C Cohort 2 - 300 mg LY2157299 + Sorafenib
    Arm/Group Description80 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 Participants377240344
    Median (90% Confidence Interval) [Weeks]
    13.4
    9.9
    19.3
    26.3
    49.3
    11. Secondary Outcome
    TitleChange From Baseline in Functional Assessment of Cancer Therapy, Hepatobiliary (FACT-Hep) Sub-scores and Total Score
    DescriptionFACT-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 FrameBaseline, 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 TitlePart A Cohort 1 - 160 mg LY2157299Part A Cohort 2 - 300 mg LY2157299Part B - 300 mg LY2157299Part C Cohort 1 - 160mg LY2157299 + SorafenibPart C Cohort 2 - 300 mg LY2157299 + Sorafenib
    Arm/Group Description80 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 Participants305138339
    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
    TitleTime to Worsening (TTW) of Symptoms (FACT-Hep)
    DescriptionTime 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 FrameBaseline 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 TitlePart A Cohort 1 - 160 mg LY2157299Part A Cohort 2 - 300 mg LY2157299Part B - 300 mg LY2157299Part C Cohort 2 - 300mg LY2157299
    Arm/Group Description80 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 Participants30613740
    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 FrameBaseline 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 TitlePart A Cohort 1 - 160 mg LY2157299Part A Cohort 2 - 300 mg LY2157299Part B - 300 mg LY2157299Part C Cohort 1 - 160 mg LY2157299 + SorafenibPart C Cohort 2 - 300 mg LY2157299 + SorafenibPart D Cohort 1 - 160 mg LY2157299 + RamucirumabPart D Cohort 2 - 300 mg LY2157299 + Ramucirumab
    Arm/Group Description80 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 LY2157299Part A Cohort 2 - 300 mg LY2157299Part B - 300 mg LY2157299Part C Cohort 1 - 160 mg LY2157299 + SorafenibPart C Cohort 2 - 300 mg LY2157299 + SorafenibPart D Cohort 1 - 160 mg LY2157299 + RamucirumabPart D Cohort 2 - 300 mg LY2157299 + Ramucirumab
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total33/37 (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 LY2157299Part A Cohort 2 - 300 mg LY2157299Part B - 300 mg LY2157299Part C Cohort 1 - 160 mg LY2157299 + SorafenibPart C Cohort 2 - 300 mg LY2157299 + SorafenibPart D Cohort 1 - 160 mg LY2157299 + RamucirumabPart D Cohort 2 - 300 mg LY2157299 + Ramucirumab
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total15/37 (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
    Anaemia2/37 (5.4%) 27/72 (9.7%) 163/40 (7.5%) 51/3 (33.3%) 26/44 (13.6%) 90/3 (0%) 00/5 (0%) 0
    Neutropenia0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Thrombocytopenia0/37 (0%) 00/72 (0%) 01/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Cardiac disorders
    Acute coronary syndrome0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Acute myocardial infarction1/37 (2.7%) 10/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Angina unstable0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Atrial fibrillation0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Atrial thrombosis0/37 (0%) 00/72 (0%) 01/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Cardiac failure0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Left ventricular dysfunction0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Left ventricular failure1/37 (2.7%) 10/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Gastrointestinal disorders
    Abdominal distension0/37 (0%) 01/72 (1.4%) 20/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Abdominal pain0/37 (0%) 03/72 (4.2%) 31/40 (2.5%) 10/3 (0%) 01/44 (2.3%) 20/3 (0%) 00/5 (0%) 0
    Abdominal pain upper0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Ascites2/37 (5.4%) 24/72 (5.6%) 61/40 (2.5%) 10/3 (0%) 02/44 (4.5%) 20/3 (0%) 00/5 (0%) 0
    Diarrhoea0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Duodenal ulcer0/37 (0%) 00/72 (0%) 00/40 (0%) 01/3 (33.3%) 10/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Gastric ulcer0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Gastric varices haemorrhage0/37 (0%) 01/72 (1.4%) 11/40 (2.5%) 20/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Gastrointestinal haemorrhage0/37 (0%) 01/72 (1.4%) 21/40 (2.5%) 11/3 (33.3%) 10/44 (0%) 00/3 (0%) 01/5 (20%) 1
    Haematemesis0/37 (0%) 00/72 (0%) 01/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Intestinal obstruction0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Intra-abdominal haemorrhage1/37 (2.7%) 10/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Large intestinal haemorrhage1/37 (2.7%) 10/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Lower gastrointestinal haemorrhage1/37 (2.7%) 10/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Melaena0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Nausea0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Oesophageal varices haemorrhage1/37 (2.7%) 11/72 (1.4%) 11/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Pancreatitis1/37 (2.7%) 11/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Peritoneal haematoma0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Peritoneal haemorrhage0/37 (0%) 01/72 (1.4%) 11/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Rectal haemorrhage0/37 (0%) 01/72 (1.4%) 30/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Small intestinal haemorrhage0/37 (0%) 01/72 (1.4%) 20/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Subileus1/37 (2.7%) 10/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Upper gastrointestinal haemorrhage0/37 (0%) 01/72 (1.4%) 12/40 (5%) 41/3 (33.3%) 11/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Varices oesophageal0/37 (0%) 01/72 (1.4%) 12/40 (5%) 30/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Vomiting0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    General disorders
    Asthenia1/37 (2.7%) 11/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Chest discomfort1/37 (2.7%) 10/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    General physical health deterioration0/37 (0%) 00/72 (0%) 00/40 (0%) 01/3 (33.3%) 10/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Pain1/37 (2.7%) 10/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Pyrexia1/37 (2.7%) 12/72 (2.8%) 20/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Hepatobiliary disorders
    Acute hepatic failure0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 01/5 (20%) 1
    Gallbladder rupture0/37 (0%) 00/72 (0%) 01/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Hepatic failure1/37 (2.7%) 12/72 (2.8%) 20/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Hepatic haematoma0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Hepatic haemorrhage1/37 (2.7%) 12/72 (2.8%) 20/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Hepatic pain0/37 (0%) 02/72 (2.8%) 21/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Hepatorenal syndrome0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Hyperbilirubinaemia1/37 (2.7%) 10/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Jaundice cholestatic1/37 (2.7%) 10/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Portal vein thrombosis0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Infections and infestations
    Anal abscess0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Arthritis bacterial0/37 (0%) 00/72 (0%) 01/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Cellulitis1/37 (2.7%) 10/72 (0%) 01/40 (2.5%) 20/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Diverticulitis0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Endocarditis0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Liver abscess0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 02/44 (4.5%) 20/3 (0%) 00/5 (0%) 0
    Lower respiratory tract infection1/37 (2.7%) 10/72 (0%) 01/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Lung infection0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 20/3 (0%) 00/5 (0%) 0
    Osteomyelitis0/37 (0%) 00/72 (0%) 01/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Peritonitis bacterial0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Pneumonia0/37 (0%) 04/72 (5.6%) 40/40 (0%) 00/3 (0%) 01/44 (2.3%) 20/3 (0%) 00/5 (0%) 0
    Sepsis0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 02/44 (4.5%) 20/3 (0%) 00/5 (0%) 0
    Urinary tract infection0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Wound infection0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Injury, poisoning and procedural complications
    Cervical vertebral fracture0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Concussion0/37 (0%) 00/72 (0%) 01/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Exposure during pregnancy0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Femur fracture1/37 (2.7%) 11/72 (1.4%) 11/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Pelvic fracture0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Post procedural haemorrhage0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Radiation pneumonitis0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Shunt stenosis0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Toxicity to various agents0/37 (0%) 01/72 (1.4%) 11/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Investigations
    Blood bilirubin increased1/37 (2.7%) 10/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Liver function test abnormal0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite1/37 (2.7%) 10/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Dehydration0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Fluid retention1/37 (2.7%) 10/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Hyperammonaemia1/37 (2.7%) 10/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Hyperglycaemia1/37 (2.7%) 11/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain0/37 (0%) 02/72 (2.8%) 20/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Chondrocalcinosis pyrophosphate0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Joint effusion0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Musculoskeletal pain0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Myalgia0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Osteoarthritis0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant ascites0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Malignant neoplasm progression0/37 (0%) 00/72 (0%) 01/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Neoplasm progression1/37 (2.7%) 10/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Pancreatic neuroendocrine tumour0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 01/5 (20%) 1
    Second primary malignancy0/37 (0%) 00/72 (0%) 00/40 (0%) 01/3 (33.3%) 10/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Squamous cell carcinoma0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Squamous cell carcinoma of lung0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Squamous cell carcinoma of skin0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Tumour haemorrhage0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Tumour pain2/37 (5.4%) 30/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Nervous system disorders
    Cerebrovascular accident0/37 (0%) 00/72 (0%) 01/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Embolic stroke0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 01/3 (33.3%) 10/5 (0%) 0
    Encephalopathy1/37 (2.7%) 12/72 (2.8%) 20/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Haemorrhage intracranial0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Hepatic encephalopathy2/37 (5.4%) 31/72 (1.4%) 11/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 01/5 (20%) 1
    Loss of consciousness0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Presyncope0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Transient ischaemic attack0/37 (0%) 00/72 (0%) 01/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Psychiatric disorders
    Confusional state1/37 (2.7%) 20/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Disorientation0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Renal and urinary disorders
    Acute kidney injury1/37 (2.7%) 12/72 (2.8%) 20/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Haematuria0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 20/3 (0%) 00/5 (0%) 0
    Prerenal failure1/37 (2.7%) 10/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Renal disorder0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Renal impairment0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Renal injury0/37 (0%) 00/72 (0%) 00/40 (0%) 01/3 (33.3%) 10/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Urinary retention0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea0/37 (0%) 01/72 (1.4%) 11/40 (2.5%) 30/3 (0%) 02/44 (4.5%) 20/3 (0%) 00/5 (0%) 0
    Pleural effusion0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Pneumonia aspiration0/37 (0%) 00/72 (0%) 01/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Pneumonitis0/37 (0%) 00/72 (0%) 01/40 (2.5%) 10/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Pulmonary embolism1/37 (2.7%) 10/72 (0%) 02/40 (5%) 21/3 (33.3%) 11/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Pulmonary infarction0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Pulmonary oedema1/37 (2.7%) 10/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Respiratory failure0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Skin and subcutaneous tissue disorders
    Drug eruption0/37 (0%) 00/72 (0%) 01/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Vascular disorders
    Dry gangrene0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Shock haemorrhagic0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Thrombosis1/37 (2.7%) 10/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Other (Not Including Serious) Adverse Events
    Part A Cohort 1 - 160 mg LY2157299Part A Cohort 2 - 300 mg LY2157299Part B - 300 mg LY2157299Part C Cohort 1 - 160 mg LY2157299 + SorafenibPart C Cohort 2 - 300 mg LY2157299 + SorafenibPart D Cohort 1 - 160 mg LY2157299 + RamucirumabPart D Cohort 2 - 300 mg LY2157299 + Ramucirumab
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total32/37 (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
    Anaemia9/37 (24.3%) 2213/72 (18.1%) 2310/40 (25%) 201/3 (33.3%) 412/44 (27.3%) 170/3 (0%) 00/5 (0%) 0
    Neutropenia3/37 (8.1%) 93/72 (4.2%) 41/40 (2.5%) 10/3 (0%) 01/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Thrombocytopenia2/37 (5.4%) 22/72 (2.8%) 23/40 (7.5%) 90/3 (0%) 07/44 (15.9%) 220/3 (0%) 00/5 (0%) 0
    Ear and labyrinth disorders
    Tinnitus0/37 (0%) 00/72 (0%) 03/40 (7.5%) 30/3 (0%) 02/44 (4.5%) 20/3 (0%) 00/5 (0%) 0
    Vertigo0/37 (0%) 01/72 (1.4%) 11/40 (2.5%) 11/3 (33.3%) 10/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Gastrointestinal disorders
    Abdominal distension2/37 (5.4%) 32/72 (2.8%) 25/40 (12.5%) 50/3 (0%) 04/44 (9.1%) 41/3 (33.3%) 12/5 (40%) 2
    Abdominal pain7/37 (18.9%) 711/72 (15.3%) 128/40 (20%) 101/3 (33.3%) 17/44 (15.9%) 80/3 (0%) 02/5 (40%) 2
    Abdominal pain upper1/37 (2.7%) 17/72 (9.7%) 104/40 (10%) 40/3 (0%) 04/44 (9.1%) 50/3 (0%) 01/5 (20%) 1
    Ascites5/37 (13.5%) 78/72 (11.1%) 82/40 (5%) 30/3 (0%) 06/44 (13.6%) 80/3 (0%) 00/5 (0%) 0
    Barrett's oesophagus0/37 (0%) 00/72 (0%) 00/40 (0%) 01/3 (33.3%) 10/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Constipation5/37 (13.5%) 611/72 (15.3%) 147/40 (17.5%) 70/3 (0%) 06/44 (13.6%) 80/3 (0%) 01/5 (20%) 1
    Diarrhoea5/37 (13.5%) 810/72 (13.9%) 1311/40 (27.5%) 151/3 (33.3%) 221/44 (47.7%) 431/3 (33.3%) 11/5 (20%) 1
    Dry mouth1/37 (2.7%) 14/72 (5.6%) 42/40 (5%) 21/3 (33.3%) 12/44 (4.5%) 21/3 (33.3%) 10/5 (0%) 0
    Flatulence2/37 (5.4%) 30/72 (0%) 01/40 (2.5%) 12/3 (66.7%) 23/44 (6.8%) 30/3 (0%) 00/5 (0%) 0
    Gingival bleeding0/37 (0%) 00/72 (0%) 00/40 (0%) 01/3 (33.3%) 10/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Nausea6/37 (16.2%) 1115/72 (20.8%) 219/40 (22.5%) 91/3 (33.3%) 212/44 (27.3%) 171/3 (33.3%) 11/5 (20%) 1
    Portal hypertensive gastropathy0/37 (0%) 00/72 (0%) 00/40 (0%) 01/3 (33.3%) 10/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Stomatitis1/37 (2.7%) 13/72 (4.2%) 30/40 (0%) 00/3 (0%) 05/44 (11.4%) 80/3 (0%) 00/5 (0%) 0
    Varices oesophageal0/37 (0%) 02/72 (2.8%) 21/40 (2.5%) 11/3 (33.3%) 10/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Vomiting6/37 (16.2%) 612/72 (16.7%) 176/40 (15%) 111/3 (33.3%) 15/44 (11.4%) 110/3 (0%) 00/5 (0%) 0
    General disorders
    Asthenia5/37 (13.5%) 66/72 (8.3%) 64/40 (10%) 80/3 (0%) 06/44 (13.6%) 140/3 (0%) 00/5 (0%) 0
    Chills3/37 (8.1%) 32/72 (2.8%) 30/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 01/5 (20%) 1
    Fatigue9/37 (24.3%) 1014/72 (19.4%) 1714/40 (35%) 152/3 (66.7%) 211/44 (25%) 160/3 (0%) 02/5 (40%) 4
    Influenza like illness1/37 (2.7%) 11/72 (1.4%) 14/40 (10%) 40/3 (0%) 03/44 (6.8%) 30/3 (0%) 00/5 (0%) 0
    Localised oedema0/37 (0%) 01/72 (1.4%) 10/40 (0%) 01/3 (33.3%) 10/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Non-cardiac chest pain0/37 (0%) 02/72 (2.8%) 21/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 01/5 (20%) 1
    Oedema peripheral5/37 (13.5%) 614/72 (19.4%) 1612/40 (30%) 170/3 (0%) 010/44 (22.7%) 121/3 (33.3%) 11/5 (20%) 1
    Pain0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 01/5 (20%) 1
    Pyrexia2/37 (5.4%) 46/72 (8.3%) 82/40 (5%) 21/3 (33.3%) 15/44 (11.4%) 130/3 (0%) 01/5 (20%) 1
    Hepatobiliary disorders
    Hyperbilirubinaemia3/37 (8.1%) 53/72 (4.2%) 31/40 (2.5%) 10/3 (0%) 04/44 (9.1%) 50/3 (0%) 00/5 (0%) 0
    Portal vein thrombosis0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 01/5 (20%) 1
    Infections and infestations
    Bronchitis0/37 (0%) 03/72 (4.2%) 34/40 (10%) 40/3 (0%) 02/44 (4.5%) 20/3 (0%) 00/5 (0%) 0
    Furuncle0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 03/44 (6.8%) 30/3 (0%) 00/5 (0%) 0
    Lung infection0/37 (0%) 00/72 (0%) 01/40 (2.5%) 10/3 (0%) 03/44 (6.8%) 70/3 (0%) 00/5 (0%) 0
    Post abortion infection0/5 (0%) 00/13 (0%) 00/4 (0%) 00/0 (NaN) 01/5 (20%) 10/0 (NaN) 00/0 (NaN) 0
    Upper respiratory tract infection1/37 (2.7%) 11/72 (1.4%) 11/40 (2.5%) 10/3 (0%) 02/44 (4.5%) 31/3 (33.3%) 10/5 (0%) 0
    Urinary tract infection0/37 (0%) 02/72 (2.8%) 21/40 (2.5%) 21/3 (33.3%) 15/44 (11.4%) 50/3 (0%) 00/5 (0%) 0
    Vaginal infection0/5 (0%) 00/13 (0%) 00/4 (0%) 00/0 (NaN) 01/5 (20%) 10/0 (NaN) 00/0 (NaN) 0
    Viral infection0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 01/3 (33.3%) 10/5 (0%) 0
    Vulvovaginal candidiasis0/5 (0%) 00/13 (0%) 00/4 (0%) 00/0 (NaN) 01/5 (20%) 10/0 (NaN) 00/0 (NaN) 0
    Injury, poisoning and procedural complications
    Fall0/37 (0%) 00/72 (0%) 00/40 (0%) 01/3 (33.3%) 10/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Investigations
    Aspartate aminotransferase increased2/37 (5.4%) 33/72 (4.2%) 32/40 (5%) 21/3 (33.3%) 13/44 (6.8%) 30/3 (0%) 00/5 (0%) 0
    Blood alkaline phosphatase increased0/37 (0%) 01/72 (1.4%) 11/40 (2.5%) 11/3 (33.3%) 12/44 (4.5%) 20/3 (0%) 00/5 (0%) 0
    Blood bilirubin increased1/37 (2.7%) 13/72 (4.2%) 32/40 (5%) 20/3 (0%) 01/44 (2.3%) 10/3 (0%) 01/5 (20%) 1
    Haemoglobin decreased0/37 (0%) 00/72 (0%) 00/40 (0%) 01/3 (33.3%) 10/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Weight decreased4/37 (10.8%) 58/72 (11.1%) 810/40 (25%) 173/3 (100%) 724/44 (54.5%) 580/3 (0%) 00/5 (0%) 0
    Weight increased1/37 (2.7%) 17/72 (9.7%) 81/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite6/37 (16.2%) 77/72 (9.7%) 87/40 (17.5%) 72/3 (66.7%) 210/44 (22.7%) 150/3 (0%) 00/5 (0%) 0
    Hypercalcaemia3/37 (8.1%) 41/72 (1.4%) 20/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Hypoalbuminaemia0/37 (0%) 03/72 (4.2%) 42/40 (5%) 30/3 (0%) 03/44 (6.8%) 30/3 (0%) 00/5 (0%) 0
    Hypokalaemia0/37 (0%) 01/72 (1.4%) 11/40 (2.5%) 10/3 (0%) 04/44 (9.1%) 60/3 (0%) 00/5 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia3/37 (8.1%) 53/72 (4.2%) 35/40 (12.5%) 50/3 (0%) 06/44 (13.6%) 60/3 (0%) 00/5 (0%) 0
    Back pain2/37 (5.4%) 35/72 (6.9%) 91/40 (2.5%) 20/3 (0%) 03/44 (6.8%) 30/3 (0%) 00/5 (0%) 0
    Muscle spasms2/37 (5.4%) 22/72 (2.8%) 35/40 (12.5%) 70/3 (0%) 06/44 (13.6%) 70/3 (0%) 00/5 (0%) 0
    Muscular weakness0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 11/3 (33.3%) 10/5 (0%) 0
    Musculoskeletal chest pain0/37 (0%) 02/72 (2.8%) 31/40 (2.5%) 10/3 (0%) 01/44 (2.3%) 12/3 (66.7%) 20/5 (0%) 0
    Myalgia1/37 (2.7%) 11/72 (1.4%) 11/40 (2.5%) 10/3 (0%) 010/44 (22.7%) 110/3 (0%) 00/5 (0%) 0
    Pain in extremity1/37 (2.7%) 13/72 (4.2%) 31/40 (2.5%) 20/3 (0%) 03/44 (6.8%) 60/3 (0%) 00/5 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma0/37 (0%) 00/72 (0%) 01/40 (2.5%) 11/3 (33.3%) 10/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Malignant ascites1/37 (2.7%) 15/72 (6.9%) 51/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Tumour pain4/37 (10.8%) 41/72 (1.4%) 11/40 (2.5%) 10/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Nervous system disorders
    Embolic stroke0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 01/3 (33.3%) 10/5 (0%) 0
    Headache1/37 (2.7%) 14/72 (5.6%) 45/40 (12.5%) 50/3 (0%) 03/44 (6.8%) 30/3 (0%) 01/5 (20%) 1
    Hepatic encephalopathy2/37 (5.4%) 20/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Peripheral sensory neuropathy3/37 (8.1%) 30/72 (0%) 00/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Somnolence2/37 (5.4%) 21/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Taste disorder1/37 (2.7%) 10/72 (0%) 00/40 (0%) 00/3 (0%) 01/44 (2.3%) 10/3 (0%) 01/5 (20%) 1
    Psychiatric disorders
    Anxiety1/37 (2.7%) 14/72 (5.6%) 40/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Confusional state2/37 (5.4%) 21/72 (1.4%) 10/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 01/5 (20%) 1
    Insomnia2/37 (5.4%) 25/72 (6.9%) 64/40 (10%) 40/3 (0%) 05/44 (11.4%) 50/3 (0%) 00/5 (0%) 0
    Renal and urinary disorders
    Haematuria1/37 (2.7%) 10/72 (0%) 00/40 (0%) 00/3 (0%) 03/44 (6.8%) 30/3 (0%) 00/5 (0%) 0
    Nocturia0/37 (0%) 02/72 (2.8%) 20/40 (0%) 00/3 (0%) 00/44 (0%) 00/3 (0%) 01/5 (20%) 1
    Reproductive system and breast disorders
    Erectile dysfunction1/32 (3.1%) 10/59 (0%) 00/36 (0%) 00/3 (0%) 02/39 (5.1%) 20/3 (0%) 00/5 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Cough3/37 (8.1%) 35/72 (6.9%) 53/40 (7.5%) 40/3 (0%) 03/44 (6.8%) 40/3 (0%) 01/5 (20%) 1
    Dyspnoea3/37 (8.1%) 39/72 (12.5%) 106/40 (15%) 70/3 (0%) 05/44 (11.4%) 51/3 (33.3%) 11/5 (20%) 2
    Epistaxis1/37 (2.7%) 32/72 (2.8%) 23/40 (7.5%) 30/3 (0%) 04/44 (9.1%) 53/3 (100%) 31/5 (20%) 1
    Oropharyngeal pain1/37 (2.7%) 11/72 (1.4%) 11/40 (2.5%) 10/3 (0%) 01/44 (2.3%) 10/3 (0%) 01/5 (20%) 1
    Skin and subcutaneous tissue disorders
    Alopecia0/37 (0%) 01/72 (1.4%) 10/40 (0%) 00/3 (0%) 09/44 (20.5%) 90/3 (0%) 00/5 (0%) 0
    Dry skin1/37 (2.7%) 13/72 (4.2%) 31/40 (2.5%) 10/3 (0%) 07/44 (15.9%) 70/3 (0%) 00/5 (0%) 0
    Erythema multiforme0/37 (0%) 01/72 (1.4%) 11/40 (2.5%) 11/3 (33.3%) 11/44 (2.3%) 10/3 (0%) 00/5 (0%) 0
    Night sweats2/37 (5.4%) 20/72 (0%) 00/40 (0%) 01/3 (33.3%) 10/44 (0%) 00/3 (0%) 00/5 (0%) 0
    Palmar-plantar erythrodysaesthesia syndrome0/37 (0%) 01/72 (1.4%) 11/40 (2.5%) 11/3 (33.3%) 328/44 (63.6%) 610/3 (0%) 00/5 (0%) 0
    Pruritus7/37 (18.9%) 99/72 (12.5%) 108/40 (20%) 101/3 (33.3%) 112/44 (27.3%) 160/3 (0%) 00/5 (0%) 0
    Rash0/37 (0%) 01/72 (1.4%) 10/40 (0%) 01/3 (33.3%) 310/44 (22.7%) 110/3 (0%) 00/5 (0%) 0
    Rash maculo-papular3/37 (8.1%) 31/72 (1.4%) 12/40 (5%) 21/3 (33.3%) 11/44 (2.3%) 20/3 (0%) 00/5 (0%) 0
    Skin exfoliation0/37 (0%) 00/72 (0%) 00/40 (0%) 00/3 (0%) 03/44 (6.8%) 30/3 (0%) 00/5 (0%) 0
    Skin lesion1/37 (2.7%) 10/72 (0%) 00/40 (0%) 00/3 (0%) 03/44 (6.8%) 30/3 (0%) 00/5 (0%) 0
    Vascular disorders
    Flushing0/37 (0%) 02/72 (2.8%) 30/40 (0%) 00/3 (0%) 03/44 (6.8%) 30/3 (0%) 00/5 (0%) 0
    Haematoma0/37 (0%) 01/72 (1.4%) 11/40 (2.5%) 10/3 (0%) 04/44 (9.1%) 40/3 (0%) 00/5 (0%) 0
    Hypertension0/37 (0%) 01/72 (1.4%) 12/40 (5%) 20/3 (0%) 08/44 (18.2%) 100/3 (0%) 00/5 (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.

    Results Point of Contact

    Name/TitleChief Medical Officer
    OrganizationEli Lilly and Company
    Phone800-545-5979
    EmailClinicalTrials.gov@lilly.com
    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