A Study of LY2157299 in Participants With Advanced Hepatocellular Carcinoma

OS defined as the time from the date of randomization to the date of death due to any cause. An overall survival event was defined as death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive. The number of participants with overall survival events (deaths) is reported.

Time frame: Randomization to Date of Death from Any Cause (Up To 24 Months)

Population: All randomized participants. Censored participants: Galunisertib Monotherapy =5, Galunisertib Plus Sorafenib Therapy = 16 and Sorafenib Plus Placebo Therapy = 7.

The EORTC QLQ-HCC-18 was an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30. EORTC QLQ-HCC 18 questionnaire included 8 symptom scales such as abdominal swelling, sex life, fatigue, body image, jaundice, nutrition, pain and fever. Each individual item ranges from 1 to 4, where 1 = not at all and 4 = very much. All domain scores were calculated as an average of item scores and transformed to 0 to 100 score range. A high score for a symptom scale/item represented a high level of symptomatology/problem.

Time frame: Baseline, 24 Months

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline EORTC-QLQ HCC-18 data for each EORTC-QLQ HCC-18 items.

EORTC QLQ-C30 consists of 30 items covered by 1 of 3 dimensions: 1. Global health status/quality of life (2 items) with scores ranging from 1 (Very Poor) to 7 (Excellent). 2. Functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), each item scores ranging from 1 (not at all) to 4 (very much). 3. Symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhea, or financial impact), each item scores ranging from 1 (not at all) to 4 (very much). All domain scores were calculated as an average of item scores and transformed to 0 to 100 score range. A high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/quality of life (QoL) represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problem.

Time frame: Baseline, 24 Months

Population: All randomized participants who received at least one dose of study drug and with baseline and post-baseline EORTC QLQ-C30 data for each EORTC QLQ-C30 items.

ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.

Time frame: Randomization to Measured Progressive Disease (Up To 24 Months)

Population: All randomized participants.

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

Population: All randomized participants who received at least one dose of study drug, with evaluable galunisertib PK data. The analyses conducted on galunisertib exposure parameter from both arms combined per the statistical analysis plan, as monotherapy and combination arm showed no difference in galunisertib PK.

Population Vss \[distribution of galunisertib in the body at steady state\] after a single dose of galunisertib.

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

Population: All randomized participants who received at least one dose of study drug, with evaluable galunisertib PK data. The analyses conducted on galunisertib exposure parameter from both arms combined per the statistical analysis plan, as monotherapy and combination arm showed no difference in galunisertib PK.

PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.

Time frame: Randomization to Measured Progressive Disease or Death (Up To 24 Months)

Population: All randomized participants. Censored participants: Galunisertib Monotherapy =1, Galunisertib Plus Sorafenib Therapy = 8 and Sorafenib Plus Placebo Therapy = 5.

TTP at initial treatment was defined as the number of months between date of randomization and the date of first documented disease progression or the date of death due to disease under study, whichever came first. Progression was assessed by the Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.Progressive Disease (PD)is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Time frame: Randomization to the Date of Objective Progressive Disease or Date of Death due to Study Disease, whichever came first (Up To 24 Months)

Population: All randomized participants. Censored participants: Galunisertib Monotherapy =2, Galunisertib Plus Sorafenib Therapy = 15 and Sorafenib Plus Placebo Therapy = 9.