Trial Outcomes & Findings for A Phase 2 Study of Cabozantinib in Japanese Participants With Advanced Hepatocellular Carcinoma (NCT NCT03586973)

Last Updated: 2023-04-18

Results Overview

24-week PFSR=percentage of participants with progression-free survival (PFS) of at least 24 weeks at Week 25 Day 1 plus 7 days. PFS=time from first day of study drug administration to earlier of progressive disease (PD) or death due to any cause per Response Evaluation Criteria in Solid Tumors Version 1.1(RECIST 1.1). PD=at least a 20% increase in sum of target lesion diameters (SoD) with reference to smallest(nadir) SoD. In addition to relative increase of 20%, SoD must also demonstrate an absolute increase of at least 5 mm. For nontarget lesion time Point Response, unequivocal progression of nontarget lesions. Modest 'increase' in size of one or more nontarget lesions is usually not sufficient to quality for unequivocal progression status, it must not be representative of single lesion increase. Lesion in an anatomical location and not scanned at baseline is considered new lesion. Lesion qualifies as PD if finding is unequivocally not due to change in imaging technique or modality.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

34 participants

Primary outcome timeframe

Week 25 Day 1 plus 7 days

Results posted on

2023-04-18

Participant Flow

Participants took part in the study at 15 investigative sites in Japan from 06 August 2018 to 29 June 2021.

Participants with a diagnosis of advanced hepatocellular carcinoma (HCC) were enrolled in this study in two Cohorts A and B. Participants who received prior sorafenib were enrolled in Cohort A and participants who received prior systemic anticancer therapy other than sorafenib were enrolled in Cohort B.

Participant milestones

Participant milestones
Measure	Cohort A: Cabozantinib 60 mg Participants who have received first/second line anticancer therapy with sorafenib were assigned to Cohort A and received cabozantinib 60 milligrams (mg), tablet, orally, once daily in the fasted state, up to approximately 2 years.	Cohort B: Cabozantinib 60 mg Participants who did not receive first/second line anticancer therapy with sorafenib were assigned to Cohort B and received cabozantinib 60 mg, tablet orally, once daily in the fasted state, up to approximately 2 years.
Overall Study STARTED	20	14
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	20	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort A: Cabozantinib 60 mg Participants who have received first/second line anticancer therapy with sorafenib were assigned to Cohort A and received cabozantinib 60 milligrams (mg), tablet, orally, once daily in the fasted state, up to approximately 2 years.	Cohort B: Cabozantinib 60 mg Participants who did not receive first/second line anticancer therapy with sorafenib were assigned to Cohort B and received cabozantinib 60 mg, tablet orally, once daily in the fasted state, up to approximately 2 years.
Overall Study Death	15	8
Overall Study Site Terminated by Sponsor	3	6
Overall Study Withdrawal by Subject	1	0
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

A Phase 2 Study of Cabozantinib in Japanese Participants With Advanced Hepatocellular Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A: Cabozantinib 60 mg n=20 Participants Participants who have received first/second line anticancer therapy with sorafenib were assigned to Cohort A and received cabozantinib 60 milligrams (mg), tablet, orally, once daily in the fasted state, up to approximately 2 years.	Cohort B: Cabozantinib 60 mg n=14 Participants Participants who did not receive first/second line anticancer therapy with sorafenib were assigned to Cohort B and received cabozantinib 60 mg, tablet orally, once daily in the fasted state, up to approximately 2 years.	Total n=34 Participants Total of all reporting groups
Age, Continuous	72.2 years STANDARD_DEVIATION 6.32 • n=5 Participants	71.6 years STANDARD_DEVIATION 8.13 • n=7 Participants	72 years STANDARD_DEVIATION 7.01 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	14 Participants n=7 Participants	31 Participants n=5 Participants
Race/Ethnicity, Customized Asian	20 Participants n=5 Participants	14 Participants n=7 Participants	34 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	20 Participants n=5 Participants	14 Participants n=7 Participants	34 Participants n=5 Participants
Region of Enrollment Japan	20 Participants n=5 Participants	14 Participants n=7 Participants	34 Participants n=5 Participants
Height	162.2 centimeter (cm) STANDARD_DEVIATION 8.31 • n=5 Participants	165.4 centimeter (cm) STANDARD_DEVIATION 7.08 • n=7 Participants	163.5 centimeter (cm) STANDARD_DEVIATION 7.88 • n=5 Participants
Weight	61.60 kilogram (kg) STANDARD_DEVIATION 9.123 • n=5 Participants	64.54 kilogram (kg) STANDARD_DEVIATION 11.351 • n=7 Participants	62.81 kilogram (kg) STANDARD_DEVIATION 10.042 • n=5 Participants
Body Mass Index (BMI)	23.34 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.262 • n=5 Participants	23.46 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.894 • n=7 Participants	23.39 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.5 • n=5 Participants
History of Drinking Alcohol Current Drinker	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
History of Drinking Alcohol Former Drinker	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants
History of Drinking Alcohol Never Drunk	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Current Etiology of Disease Hepatitis B (Without Hepatitis C)	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Current Etiology of Disease Hepatitis C (Without Hepatitis B)	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Current Etiology of Disease Hepatitis B and C	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Current Etiology of Disease Hepatitis B (Regardless of Hepatitis C)	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Current Etiology of Disease Hepatitis C (Regardless of Hepatitis B)	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Current Etiology of Disease Without Hepatitis B and C	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Current Etiology of Disease Alcoholism	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Current Etiology of Disease Nonalcoholic Steatohepatitis (NASH)	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Current Etiology of Disease Other	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Child-Pugh Score: Grade A	20 Participants n=5 Participants	14 Participants n=7 Participants	34 Participants n=5 Participants
Extrahepatic Spread and/or Macrovascular Invasion Presence	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Extrahepatic Spread and/or Macrovascular Invasion No presence	13 Participants n=5 Participants	8 Participants n=7 Participants	21 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): Grade 1	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 25 Day 1 plus 7 days

Population: Full Analysis Set (FAS) included participants who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	Cohort A: Cabozantinib 60 mg n=20 Participants Participants who have received first/second line anticancer therapy with sorafenib were assigned to Cohort A and received cabozantinib 60 milligrams (mg), tablet, orally, once daily in the fasted state, up to approximately 2 years.	Cohort B: Cabozantinib 60 mg n=14 Participants Participants who did not receive first/second line anticancer therapy with sorafenib were assigned to Cohort B and received cabozantinib 60 mg, tablet orally, once daily in the fasted state, up to approximately 2 years.
24-Week Progression-Free Survival Rate (PFSR)	59.8 percentage of participants Interval 36.06 to 77.21	16.7 percentage of participants Interval 4.02 to 36.82

SECONDARY outcome

Timeframe: Until disease progression, or death or end of study (Up to approximately 2.8 years)

Population: FAS included participants who received at least one dose of study drug.

PFS was defined as time from the first day of study drug administration to the earlier of PD per RECIST 1.1 as assessed by IRC or death due to any cause. Per RECIST 1.1, for target lesion time point response, PD was defined at least a 20% increase in the SoD of target lesions, taking as a reference the smallest (nadir) SoD since (and including) baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. For nontarget lesion time point response, unequivocal progression of nontarget lesions. A modest 'increase' in the size of one or more nontarget lesions is usually not sufficient to quality for unequivocal progression status. It must be representative of overall disease status change, not a single lesion increase. The lesion qualifies as a PD if the finding is unequivocally not due to a change in the imaging technique or modality.

Outcome measures

Outcome measures
Measure	Cohort A: Cabozantinib 60 mg n=20 Participants Participants who have received first/second line anticancer therapy with sorafenib were assigned to Cohort A and received cabozantinib 60 milligrams (mg), tablet, orally, once daily in the fasted state, up to approximately 2 years.	Cohort B: Cabozantinib 60 mg n=14 Participants Participants who did not receive first/second line anticancer therapy with sorafenib were assigned to Cohort B and received cabozantinib 60 mg, tablet orally, once daily in the fasted state, up to approximately 2 years.
Progression-Free Survival (PFS)	7.4 months Interval 5.5 to 9.5	3.6 months Interval 1.8 to 5.6

SECONDARY outcome

Timeframe: Up to approximately 2 years

Population: FAS included participants who received at least one dose of study drug.

ORR was defined as the percentage of participants whose best overall response was complete response (CR) or partial response (PR) per RECIST 1.1 as assessed by IRC, which was confirmed by a subsequent evaluation conducted \>= 28 days later. Per RECIST 1.1, for target lesion time point response, CR was defined disappearance of all target lesions. All pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \<10 mm. For nontarget lesion time point response, disappearance of all nontarget lesions. All lymph nodes must be nonpathological in size (\<10 mm short axis); PR was defined as at least a 30% decrease in SoD of target lesions, taking as a reference the baseline SoD.

Outcome measures

Outcome measures
Measure	Cohort A: Cabozantinib 60 mg n=20 Participants Participants who have received first/second line anticancer therapy with sorafenib were assigned to Cohort A and received cabozantinib 60 milligrams (mg), tablet, orally, once daily in the fasted state, up to approximately 2 years.	Cohort B: Cabozantinib 60 mg n=14 Participants Participants who did not receive first/second line anticancer therapy with sorafenib were assigned to Cohort B and received cabozantinib 60 mg, tablet orally, once daily in the fasted state, up to approximately 2 years.
Objective Response Rate (ORR)	5.0 percentage of participants Interval 0.127 to 24.873	0.0 percentage of participants Interval 0.0 to 23.164

SECONDARY outcome

Timeframe: Up to approximately 2 years

Population: FAS included participants who received at least one dose of study drug.

DCR=percentage of participants whose best overall response is CR,PR or SD, per RECIST 1.1, CR and PR require confirmation by subsequent evaluation conducted \>=28 days later, and SD have to be maintained for at least 8 weeks after first day of study drug administration. CR=disappearance of all target lesions. All pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \<10 mm. For nontarget lesion time point response, disappearance of all nontarget lesions. All lymph nodes must be nonpathological in size (\<10 mm short axis); PR=at least a 30% decrease in SoD of target lesions, taking as reference baseline SoD; SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; SoD must also demonstrate an absolute increase of at least 5 mm; PD=at least a 20% increase in SoD of target lesions, taking as a reference smallest (nadir) SoD.

Outcome measures

Outcome measures
Measure	Cohort A: Cabozantinib 60 mg n=20 Participants Participants who have received first/second line anticancer therapy with sorafenib were assigned to Cohort A and received cabozantinib 60 milligrams (mg), tablet, orally, once daily in the fasted state, up to approximately 2 years.	Cohort B: Cabozantinib 60 mg n=14 Participants Participants who did not receive first/second line anticancer therapy with sorafenib were assigned to Cohort B and received cabozantinib 60 mg, tablet orally, once daily in the fasted state, up to approximately 2 years.
Disease Control Rate (DCR)	85.0 percentage of participants Interval 62.107 to 96.793	64.3 percentage of participants Interval 35.138 to 87.24

SECONDARY outcome

Timeframe: Up to end of study (Up to approximately 2.8 years)

Population: FAS included participants who received at least one dose of study drug.

OS was defined as time from the first day of study drug administration to death due to any cause. Participants without documentation of death were censored on the date they were last known to be alive.

Outcome measures

Outcome measures
Measure	Cohort A: Cabozantinib 60 mg n=20 Participants Participants who have received first/second line anticancer therapy with sorafenib were assigned to Cohort A and received cabozantinib 60 milligrams (mg), tablet, orally, once daily in the fasted state, up to approximately 2 years.	Cohort B: Cabozantinib 60 mg n=14 Participants Participants who did not receive first/second line anticancer therapy with sorafenib were assigned to Cohort B and received cabozantinib 60 mg, tablet orally, once daily in the fasted state, up to approximately 2 years.
Overall Survival (OS)	19.3 months Interval 13.3 to 22.6	9.9 months Interval 3.6 to Upper limit of 95% confidence interval was not estimable due to lower number of participants with the event.

Adverse Events

Cohort A: Cabozantinib 60 mg

Serious events: 7 serious events

Other events: 20 other events

Deaths: 15 deaths

Cohort B: Cabozantinib 60 mg

Serious events: 2 serious events

Other events: 14 other events

Deaths: 8 deaths

Serious adverse events

Serious adverse events
Measure	Cohort A: Cabozantinib 60 mg n=20 participants at risk Participants who have received first/second line anticancer therapy with sorafenib were assigned to Cohort A and received cabozantinib 60 milligrams (mg), tablet, orally, once daily in the fasted state, up to approximately 2 years.	Cohort B: Cabozantinib 60 mg n=14 participants at risk Participants who did not receive first/second line anticancer therapy with sorafenib were assigned to Cohort B and received cabozantinib 60 mg, tablet orally, once daily in the fasted state, up to approximately 2 years.
Gastrointestinal disorders Gastrointestinal ulcer	5.0% 1/20 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Ileus	5.0% 1/20 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Pyrexia	0.00% 0/20 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Cholangitis	5.0% 1/20 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Biloma	5.0% 1/20 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Cholelithiasis	5.0% 1/20 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Liver abscess	5.0% 1/20 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Meningitis bacterial	5.0% 1/20 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Peritonitis bacterial	5.0% 1/20 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hypocalcaemia	5.0% 1/20 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/14 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Hepatic encephalopathy	0.00% 0/20 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.1% 1/14 • All-Cause Mortality: Up to end of study (Up to approximately 2.8 years); Serious and other adverse events: From first dose up to 30 days post last dose (Up to approximately 2 years) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER