Trial Outcomes & Findings for Sorafenib and Nivolumab in Treating Participants With Unresectable, Locally Advanced or Metastatic Liver Cancer (NCT NCT03439891)

Last Updated: 2025-02-11

Results Overview

MTD is defined as the dose in which 1 or more dose limiting toxicities (DLT) is reported by study participants in Part 1 within the first cycle of treatment. Participants in Part 1 must receive at least 2 doses of nivolumab and at least 75% of sorafenib doses within 28 days (1 cycle), or experience a qualifying DLT event to be evaluable.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

16 participants

Primary outcome timeframe

28 days

Results posted on

2025-02-11

Participant Flow

The intent of the addition of Part 2 for Child-Pugh B participants in the protocol was to capture the differences in treatment outcomes for those with Child-Pugh A (CPA) versus Child-Pugh B (CPB). The single participant with CPB enrolled to Part 1 of the study was therefore included in some of the efficacy analyses focused on outcomes for CPB participants specifically.

Participant milestones

Participant milestones
Measure	Part 1: Starting Dose Schedule (DL -1) Once a Day Participants with Child-Pugh A or B7 receive a daily dose of 400mg sorafenib on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 1: Escalated Dose Schedule (DL 1) Twice a Day Participants with Child-Pugh A or B7 receive a daily dose of 400mg sorafenib twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 2: Child Pugh B Expansion Cohort (Sorafenib, Nivolumab) Participants with Child-Pugh B7-9 receive sorafenib at the MTD established in Part 1 on days 1-28, and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Study Cohort Assignment STARTED	6	5	5
Study Cohort Assignment COMPLETED	6	5	5
Study Cohort Assignment NOT COMPLETED	0	0	0
Parts 1 & 2: All CPB Participants STARTED	0	1	5
Parts 1 & 2: All CPB Participants COMPLETED	0	1	5
Parts 1 & 2: All CPB Participants NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Sorafenib and Nivolumab in Treating Participants With Unresectable, Locally Advanced or Metastatic Liver Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: Starting Dose Schedule (DL -1) Once a Day n=6 Participants Participants with Child-Pugh A - B7 receive a daily dose of 400mg sorafenib on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 1: Escalated Dose Schedule (DL 1) Twice a Day n=5 Participants Participants with Child-Pugh A - B7 receive a daily dose of 400mg sorafenib twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 2: Child Pugh B Expansion (Sorafenib, Nivolumab) n=5 Participants Participants with Child-Pugh B7-9 receive sorafenib at the MTD established in Part 1 on days 1-28, and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Total n=16 Participants Total of all reporting groups
Age, Continuous	64.3 years STANDARD_DEVIATION 4.5 • n=5 Participants	66 years STANDARD_DEVIATION 11.4 • n=7 Participants	67 years STANDARD_DEVIATION 6.6 • n=5 Participants	65.8 years STANDARD_DEVIATION 7.5 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	13 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	13 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	8 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	6 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants	16 participants n=4 Participants
Child-Pugh Classification and Score Child-Pugh A	6 Participants n=5 Participants	4 Participants n=7 Participants	0 Participants n=5 Participants	10 Participants n=4 Participants
Child-Pugh Classification and Score Child-Pugh B	0 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants

PRIMARY outcome

Timeframe: 28 days

Outcome measures

Outcome measures
Measure	Part 1: All Participants (Sorafenib, Nivolumab) n=11 Participants Participants with Child-Pugh A - B7 received a daily dose of 400mg sorafenib either once or twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. The course continued until 1 dose-limiting toxicity occurred to establish maximum tolerated dosing schedule.	Part 1: Escalated Dose Schedule (DL 1) Twice a Day Participants with Child-Pugh A - B7 receive a daily dose of 400mg sorafenib twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 2: Child Pugh B Expansion Cohort (Sorafenib, Nivolumab) Participants with Child-Pugh B7-9 receive sorafenib at the MTD established in Part 1 on days 1-28, and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Maximum Tolerated Dose (MTD) (Part 1 Only)	400 milligrams (mg) once per day	—	—

PRIMARY outcome

Timeframe: Up to 2 years

All adverse event (AE) will be summarized based on proportion of total participants in Part 2 to evaluate the safety of the treatment combination in participants with Child-Pugh B7-9 liver function as measured by proportion of participants with an AE of toxicity grade \>=3 as graded by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and assessed as at least possibly related to sorafenib, nivolumab, or the combination of therapies.

Outcome measures

Outcome measures
Measure	Part 1: All Participants (Sorafenib, Nivolumab) n=5 Participants Participants with Child-Pugh A - B7 received a daily dose of 400mg sorafenib either once or twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. The course continued until 1 dose-limiting toxicity occurred to establish maximum tolerated dosing schedule.	Part 1: Escalated Dose Schedule (DL 1) Twice a Day Participants with Child-Pugh A - B7 receive a daily dose of 400mg sorafenib twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 2: Child Pugh B Expansion Cohort (Sorafenib, Nivolumab) Participants with Child-Pugh B7-9 receive sorafenib at the MTD established in Part 1 on days 1-28, and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Proportion of Participants With Grade 3 or Higher Treatment-related Adverse Events (Part 2 Only)	0.6 proportion of participants	—	—

SECONDARY outcome

Timeframe: Up to 2 years

Overall rates of AE and serious adverse events (SAE) as classified by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 assessed as at least possibly related to sorafenib, nivolumab, or the combination of therapies will be reported as the proportion of participants in each arm. .

Outcome measures

Outcome measures
Measure	Part 1: All Participants (Sorafenib, Nivolumab) n=6 Participants Participants with Child-Pugh A - B7 received a daily dose of 400mg sorafenib either once or twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. The course continued until 1 dose-limiting toxicity occurred to establish maximum tolerated dosing schedule.	Part 1: Escalated Dose Schedule (DL 1) Twice a Day n=5 Participants Participants with Child-Pugh A - B7 receive a daily dose of 400mg sorafenib twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 2: Child Pugh B Expansion Cohort (Sorafenib, Nivolumab) n=5 Participants Participants with Child-Pugh B7-9 receive sorafenib at the MTD established in Part 1 on days 1-28, and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Proportion of Participants With Treatment-related Adverse Events	1.00 proportion of participants	1.00 proportion of participants	1.00 proportion of participants

SECONDARY outcome

Timeframe: Up to 2 years

Safety events for all participants assessed by treating investigator and/or Study Chair as being at least possibly immune-related while on nivolumab (irAE) will be summarized based on proportion of total participants across all treatment groups combined.

Outcome measures

Outcome measures
Measure	Part 1: All Participants (Sorafenib, Nivolumab) n=16 Participants Participants with Child-Pugh A - B7 received a daily dose of 400mg sorafenib either once or twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. The course continued until 1 dose-limiting toxicity occurred to establish maximum tolerated dosing schedule.	Part 1: Escalated Dose Schedule (DL 1) Twice a Day Participants with Child-Pugh A - B7 receive a daily dose of 400mg sorafenib twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 2: Child Pugh B Expansion Cohort (Sorafenib, Nivolumab) Participants with Child-Pugh B7-9 receive sorafenib at the MTD established in Part 1 on days 1-28, and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Proportion of Participants Reporting Immune-related Adverse Event (irAE) (Part 1 and Part 2 Combined)	0.94 proportion of participants	—	—

SECONDARY outcome

Timeframe: Up to 2 years

Safety events for all CPB participants assessed by treating investigator and/or Study Chair as being at least possibly immune-related while on nivolumab (irAE) will be summarized based on proportion of total CPB participants across all treatment groups combined.

Outcome measures

Outcome measures
Measure	Part 1: All Participants (Sorafenib, Nivolumab) n=6 Participants Participants with Child-Pugh A - B7 received a daily dose of 400mg sorafenib either once or twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. The course continued until 1 dose-limiting toxicity occurred to establish maximum tolerated dosing schedule.	Part 1: Escalated Dose Schedule (DL 1) Twice a Day Participants with Child-Pugh A - B7 receive a daily dose of 400mg sorafenib twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 2: Child Pugh B Expansion Cohort (Sorafenib, Nivolumab) Participants with Child-Pugh B7-9 receive sorafenib at the MTD established in Part 1 on days 1-28, and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Proportion of Participants With Child-Pugh B (CPB) Reporting Immune-related Adverse Event (irAE) (Parts 1 and 2 Combined)	0.83 proportion of participants	—	—

SECONDARY outcome

Timeframe: Up to 2 years

Delays in dosing due to adverse events will be summarized as proportion of participants by each arm.

Outcome measures

Outcome measures
Measure	Part 1: All Participants (Sorafenib, Nivolumab) n=6 Participants Participants with Child-Pugh A - B7 received a daily dose of 400mg sorafenib either once or twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. The course continued until 1 dose-limiting toxicity occurred to establish maximum tolerated dosing schedule.	Part 1: Escalated Dose Schedule (DL 1) Twice a Day n=5 Participants Participants with Child-Pugh A - B7 receive a daily dose of 400mg sorafenib twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 2: Child Pugh B Expansion Cohort (Sorafenib, Nivolumab) n=5 Participants Participants with Child-Pugh B7-9 receive sorafenib at the MTD established in Part 1 on days 1-28, and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Proportion of Participants With Dose Delays Due to Toxicity	0.833 proportion of participants	1.00 proportion of participants	0.8 proportion of participants

SECONDARY outcome

Timeframe: Up to 2 years

Dose reductions due to adverse events will be summarized as proportion of participants in each arm.

Outcome measures

Outcome measures
Measure	Part 1: All Participants (Sorafenib, Nivolumab) n=6 Participants Participants with Child-Pugh A - B7 received a daily dose of 400mg sorafenib either once or twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. The course continued until 1 dose-limiting toxicity occurred to establish maximum tolerated dosing schedule.	Part 1: Escalated Dose Schedule (DL 1) Twice a Day n=5 Participants Participants with Child-Pugh A - B7 receive a daily dose of 400mg sorafenib twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 2: Child Pugh B Expansion Cohort (Sorafenib, Nivolumab) n=5 Participants Participants with Child-Pugh B7-9 receive sorafenib at the MTD established in Part 1 on days 1-28, and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Proportion of Participants With Dose Reductions Due to Toxicity	0.33 proportion of participants	0.2 proportion of participants	0.4 proportion of participants

SECONDARY outcome

Timeframe: Up to 2 years

Treatment discontinuations due to adverse events will be summarized as proportion of participants in each arm.

Outcome measures

Outcome measures
Measure	Part 1: All Participants (Sorafenib, Nivolumab) n=6 Participants Participants with Child-Pugh A - B7 received a daily dose of 400mg sorafenib either once or twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. The course continued until 1 dose-limiting toxicity occurred to establish maximum tolerated dosing schedule.	Part 1: Escalated Dose Schedule (DL 1) Twice a Day n=5 Participants Participants with Child-Pugh A - B7 receive a daily dose of 400mg sorafenib twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 2: Child Pugh B Expansion Cohort (Sorafenib, Nivolumab) n=5 Participants Participants with Child-Pugh B7-9 receive sorafenib at the MTD established in Part 1 on days 1-28, and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Proportion of Participants Who Discontinued Treatment Due to Toxicity	0.167 proportion of participants	0.20 proportion of participants	0 proportion of participants

SECONDARY outcome

Timeframe: Up to 2 years

Objective response is defined as the proportion of participants assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with measurable disease at study entry who have an evaluated complete response (CR) or partial response (PR) at any time during the main study. Participants with measurable disease at study entry who have unknown or missing response information will be treated as non-responders.

Outcome measures

Outcome measures
Measure	Part 1: All Participants (Sorafenib, Nivolumab) n=16 Participants Participants with Child-Pugh A - B7 received a daily dose of 400mg sorafenib either once or twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. The course continued until 1 dose-limiting toxicity occurred to establish maximum tolerated dosing schedule.	Part 1: Escalated Dose Schedule (DL 1) Twice a Day Participants with Child-Pugh A - B7 receive a daily dose of 400mg sorafenib twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 2: Child Pugh B Expansion Cohort (Sorafenib, Nivolumab) Participants with Child-Pugh B7-9 receive sorafenib at the MTD established in Part 1 on days 1-28, and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Proportion of Participants With an Objective Response (Part 1 and Part 2 Combined)	0.063 proportion of participants	—	—

SECONDARY outcome

Timeframe: Up to 2 years

Objective response will be based on assessments using RECIST 1.15 using local radiographic review and analyzed for Part 1 and Part 2 individually. Objective response is defined as the proportion of subjects with RECIST 1.1-measurable disease at study entry who have a CR or PR at any time during the main study. Participants with measurable disease at study entry who have unknown or missing response information will be treated as non-responders.

Outcome measures

Outcome measures
Measure	Part 1: All Participants (Sorafenib, Nivolumab) n=11 Participants Participants with Child-Pugh A - B7 received a daily dose of 400mg sorafenib either once or twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. The course continued until 1 dose-limiting toxicity occurred to establish maximum tolerated dosing schedule.	Part 1: Escalated Dose Schedule (DL 1) Twice a Day n=5 Participants Participants with Child-Pugh A - B7 receive a daily dose of 400mg sorafenib twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 2: Child Pugh B Expansion Cohort (Sorafenib, Nivolumab) Participants with Child-Pugh B7-9 receive sorafenib at the MTD established in Part 1 on days 1-28, and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Proportion of Participants With an Objective Response by Part	0.09 proportion of participants	0 proportion of participants	—

SECONDARY outcome

Timeframe: Up to 2 years

DOR is defined as the median time in months from first documented evidence of complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) until the first documented sign of disease progression or death for all participant who received any treatment during the course of the study.

Outcome measures

Outcome measures
Measure	Part 1: All Participants (Sorafenib, Nivolumab) n=16 Participants Participants with Child-Pugh A - B7 received a daily dose of 400mg sorafenib either once or twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. The course continued until 1 dose-limiting toxicity occurred to establish maximum tolerated dosing schedule.	Part 1: Escalated Dose Schedule (DL 1) Twice a Day Participants with Child-Pugh A - B7 receive a daily dose of 400mg sorafenib twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 2: Child Pugh B Expansion Cohort (Sorafenib, Nivolumab) Participants with Child-Pugh B7-9 receive sorafenib at the MTD established in Part 1 on days 1-28, and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Median Duration of Response (DOR) (Part 1 and Part 2 Combined)	4.2 months Interval 4.2 to There were insufficient number of events so a confidence interval cannot be calculated	—	—

SECONDARY outcome

Timeframe: Up to 2 years

DOR is defined as the median time in months from first documented evidence of CR or PR assessed by Response Evaluation Criteria in Solid Tumors (RECIST) until the first documented sign of disease progression or death by treatment group for all participants who received treatment during the course of the study.

Outcome measures

Outcome measures
Measure	Part 1: All Participants (Sorafenib, Nivolumab) n=6 Participants Participants with Child-Pugh A - B7 received a daily dose of 400mg sorafenib either once or twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. The course continued until 1 dose-limiting toxicity occurred to establish maximum tolerated dosing schedule.	Part 1: Escalated Dose Schedule (DL 1) Twice a Day n=5 Participants Participants with Child-Pugh A - B7 receive a daily dose of 400mg sorafenib twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 2: Child Pugh B Expansion Cohort (Sorafenib, Nivolumab) n=5 Participants Participants with Child-Pugh B7-9 receive sorafenib at the MTD established in Part 1 on days 1-28, and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Median Duration of Response (DOR) by Treatment Group	4.2 months Interval 4.2 to There were insufficient number of events so a confidence interval could not be calculated	NA months There were insufficient number of events so a confidence interval could not be calculated	NA months There were insufficient number of events so a confidence interval could not be calculated

SECONDARY outcome

Timeframe: Up to 3.5 years

PFS will be calculated as the median time in months from date of first dose of protocol therapy to date of first documented radiographic and/or clinical disease progression or death from any cause for all participants who received treatment during the course of the study. For participants who discontinued from study for other reasons than progression or death, PFS will be censored at the date last date known to be progression-free for up to 2 years following the last dose of protocol therapy.

Outcome measures

Outcome measures
Measure	Part 1: All Participants (Sorafenib, Nivolumab) n=16 Participants Participants with Child-Pugh A - B7 received a daily dose of 400mg sorafenib either once or twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. The course continued until 1 dose-limiting toxicity occurred to establish maximum tolerated dosing schedule.	Part 1: Escalated Dose Schedule (DL 1) Twice a Day Participants with Child-Pugh A - B7 receive a daily dose of 400mg sorafenib twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 2: Child Pugh B Expansion Cohort (Sorafenib, Nivolumab) Participants with Child-Pugh B7-9 receive sorafenib at the MTD established in Part 1 on days 1-28, and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Median Progression-Free Survival (PFS) (Part 1 and Part 2 Combined)	2.58 months Interval 2.58 to There were insufficient number of events so a confidence interval cannot be calculated.	—	—

SECONDARY outcome

Timeframe: Up to 3.5 years

PFS will be calculated as the median time in months from date of first dose of protocol therapy to date of first documented radiographic and/or clinical disease progression or death from any cause for participants grouped by Child-Pugh Group (Class A and Class B). For participants discontinued from study for other reasons than progression or death, PFS will be censored at the date last known to be progression-free for up to 2 years following the last dose of protocol therapy.

Outcome measures

Outcome measures
Measure	Part 1: All Participants (Sorafenib, Nivolumab) n=10 Participants Participants with Child-Pugh A - B7 received a daily dose of 400mg sorafenib either once or twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. The course continued until 1 dose-limiting toxicity occurred to establish maximum tolerated dosing schedule.	Part 1: Escalated Dose Schedule (DL 1) Twice a Day n=6 Participants Participants with Child-Pugh A - B7 receive a daily dose of 400mg sorafenib twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 2: Child Pugh B Expansion Cohort (Sorafenib, Nivolumab) Participants with Child-Pugh B7-9 receive sorafenib at the MTD established in Part 1 on days 1-28, and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Median Progression-free Survival (PFS) by Child-Pugh Group	2.76 months Interval 2.76 to There were insufficient number of events so a confidence interval could not be calculated	2.58 months Interval 2.58 to There were insufficient number of events so a confidence interval could not be calculated	—

SECONDARY outcome

Timeframe: Up to 3.5 years

OS is defined as the median time in months from the date of first dose of protocol therapy to the date of death due to any cause for up to 2 years following the last dose of protocol therapy. Censoring will be performed using the date of last known contact for those who are alive at the time of analysis. If data warrant, Kaplan-Meier estimates along with the 95% confidence intervals (CI) or full range will be reported.

Outcome measures

Outcome measures
Measure	Part 1: All Participants (Sorafenib, Nivolumab) n=16 Participants Participants with Child-Pugh A - B7 received a daily dose of 400mg sorafenib either once or twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. The course continued until 1 dose-limiting toxicity occurred to establish maximum tolerated dosing schedule.	Part 1: Escalated Dose Schedule (DL 1) Twice a Day Participants with Child-Pugh A - B7 receive a daily dose of 400mg sorafenib twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 2: Child Pugh B Expansion Cohort (Sorafenib, Nivolumab) Participants with Child-Pugh B7-9 receive sorafenib at the MTD established in Part 1 on days 1-28, and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Median Overall Survival (OS) (Part 1 and Part 2 Combined)	12.99 months Interval 1.7 to 42.0	—	—

SECONDARY outcome

Timeframe: Up to 3.5 years

OS is defined as the median time in months from the date of first dose of protocol therapy to the date of death due to any cause for up to 2 years following the last dose of protocol therapy and will be reported for each of the Child-Pugh groups separately. Censoring will be performed using the date of last known contact for those who are alive at the time of analysis. If data warrant, Kaplan-Meier estimates along with the 95% confidence intervals (CI) or full range will be reported.

Outcome measures

Outcome measures
Measure	Part 1: All Participants (Sorafenib, Nivolumab) n=10 Participants Participants with Child-Pugh A - B7 received a daily dose of 400mg sorafenib either once or twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. The course continued until 1 dose-limiting toxicity occurred to establish maximum tolerated dosing schedule.	Part 1: Escalated Dose Schedule (DL 1) Twice a Day n=6 Participants Participants with Child-Pugh A - B7 receive a daily dose of 400mg sorafenib twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 2: Child Pugh B Expansion Cohort (Sorafenib, Nivolumab) Participants with Child-Pugh B7-9 receive sorafenib at the MTD established in Part 1 on days 1-28, and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Survival (OS) by Child-Pugh Group	15.26 months Interval 6.0 to 42.0	10.41 months Interval 1.7 to 36.2	—

Adverse Events

Part 1: Starting Dose Schedule (DL -1) Once a Day

Serious events: 4 serious events

Other events: 6 other events

Deaths: 5 deaths

Part 1: Escalated Dose Schedule (DL 1) Twice a Day

Serious events: 1 serious events

Other events: 5 other events

Deaths: 2 deaths

Part 2: Child Pugh B Expansion Cohort (Sorafenib, Nivolumab)

Serious events: 3 serious events

Other events: 4 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Part 1: Starting Dose Schedule (DL -1) Once a Day n=6 participants at risk Participants with Child-Pugh A - B7 receive a daily dose of 400mg sorafenib on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 1: Escalated Dose Schedule (DL 1) Twice a Day n=5 participants at risk Participants with Child-Pugh A - B7 receive a daily dose of 400mg sorafenib twice a day on days 1-28, and 240mg of nivolumab IV over 30 minutes beginning on day 15 of course 1, then on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course will continue until 1 dose-limiting toxicity occurs to establish maximum tolerated dosing schedule.	Part 2: Child Pugh B Expansion Cohort (Sorafenib, Nivolumab) n=5 participants at risk Participants with Child-Pugh B7-9 receive sorafenib at the MTD established in Part 1 on days 1-28, and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Gastrointestinal disorders Hyperbilirubinemia	0.00% 0/6 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.	20.0% 1/5 • Number of events 1 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.	0.00% 0/5 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.
Gastrointestinal disorders Small intestinal obstruction	16.7% 1/6 • Number of events 1 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.	0.00% 0/5 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.	0.00% 0/5 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.
Injury, poisoning and procedural complications Hip fracture	16.7% 1/6 • Number of events 1 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.	0.00% 0/5 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.	0.00% 0/5 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.
Metabolism and nutrition disorders Hyperglycemia	16.7% 1/6 • Number of events 1 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.	0.00% 0/5 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.	0.00% 0/5 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.
Skin and subcutaneous tissue disorders Rash maculo-papular	16.7% 1/6 • Number of events 1 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.	0.00% 0/5 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.	0.00% 0/5 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.
Infections and infestations Sepsis	0.00% 0/6 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.	0.00% 0/5 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.	20.0% 1/5 • Number of events 1 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.
Investigations Aspartate aminotransferase increased	0.00% 0/6 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.	0.00% 0/5 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.	20.0% 1/5 • Number of events 1 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.
Nervous system disorders Encephalopathy	0.00% 0/6 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.	0.00% 0/5 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.	20.0% 1/5 • Number of events 1 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.
Cardiac disorders Transient ischemic attacks	0.00% 0/6 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.	0.00% 0/5 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.	20.0% 1/5 • Number of events 1 • Up to 3.5 years Adverse events were collected per protocol and are reported according by assigned arm regardless of any investigator directed changes to the regimen occurring after cycle 1 for Part 1 participants.

Other adverse events

Additional Information

Dr. R. Katie Kelley, MD

University of California, San Francisco

Phone: (415) 353-9888

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place