Hepatocellular Carcinoma
Conditions
Keywords
MET diagnostic-high, Unresectable, Hepatocellular, Carcinoma, c-Met inhibitor
Brief summary
The purpose of this study is to determine if tivantinib (ARQ 197) is effective in treating patients with MET diagnostic-high hepatocellular carcinoma (liver cancer) who have already been treated once with another therapy.
Detailed description
Expression of c-Met in tumors correlates with aggressive hepatocellular carcinoma (HCC) features. Overexpression of the receptor in tumor samples or high level of blood HGF in subjects is related to higher recurrence rate after surgery for HCC, while high c-Met expression correlates with shorter survival in HCC subjects. In summary, c-Met holds an important prognostic role in the natural history of HCC. This Phase 3 study in MET Diagnostic-High inoperable HCC subjects has been designed based on the results from the randomized, controlled Phase 2 study conducted by ArQule, Inc. with tivantinib versus placebo in subjects with MET Diagnostic-High inoperable HCC who have failed one prior systemic therapy, mentioned above. The purpose of this study is to confirm the efficacy of tivantinib in MET Diagnostic-High HCC subjects who were previously treated with one systemic therapy, and to further evaluate the safety profile of the experimental drug in this subject population.
Interventions
DRUGTivantinib
Tivantinib tablets
DRUGPlacebo
Matching placebo tablets
Sponsors
ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed HCC that is inoperable (where surgery is not indicated due to disease extension, co-morbidities, or other technical reasons), and not eligible for local therapy * MET Diagnostic-High tissue reported by the central authorized laboratory using archival or recent biopsy tumor samples * Received at least 4 weeks of one prior sorafenib containing systemic therapy and then experienced documented radiographic disease progression; or inability to tolerate prior therapy received for at least a minimum period of time. * Discontinued prior systemic treatment or any investigational drug for at least 2 weeks (14 days) or for at least 3 weeks for IV anti-cancer drugs, prior to the study randomization * Local or loco-regional therapy (i.e., surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed \>= 4 weeks prior to randomization * Measurable disease as defined by the RECIST v1.1.
Exclusion criteria
* More than 1 prior systemic regimen (prior MET inhibitors/antibodies are not allowed; experimental systemic therapy for inoperable HCC given before or after sorafenib counts as separate regimen and is not allowed) * Child-Pugh B-C cirrhotic status based on clinical findings and laboratory results * Previous or concurrent cancer that is distinct from HCC in primary site or histology, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, and superficial bladder tumors. Any cancer curatively treated more than 3 years prior to enrollment is permitted. * History of congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification within 6 months prior to study entry; active coronary artery disease (CAD); clinically significant bradycardia or other uncontrolled, cardiac arrhythmia defined as greater than or equal to Grade 3 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), or uncontrolled hypertension; myocardial infarction occurring within 6 months prior to study entry (myocardial infarction occurring more than 6 months prior to study entry is permitted) * Active clinically serious infections defined as \>= Grade 3 according to NCI CTCAE * Any medical, psychological, or social conditions, particularly if unstable, including substance abuse, that may, in the opinion of the Investigator, interfere with the subject's safety or participation in the study, protocol compliance, or evaluation of the study results * Known human immunodeficiency virus (HIV) infection * Blood or albumin transfusion within 5 days prior to the blood draw being used to confirm eligibility * Concomitant interferon therapy or therapies for active Hepatitis C virus (HCV) infection * Pregnancy or breast-feeding * History of liver transplant * Inability to swallow oral medications * Clinically significant gastrointestinal bleeding occurring \<= 4 weeks prior to randomization * Pleural effusion or clinically evident (visible or palpable) ascites
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival (OS) Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | within 36 months | Overall survival (OS) is defined as the time from randomization to the date of death. The rate of OS (percentage of participants still alive) was determined only in the tivantinib 120 mg BID cohort. |
| Overall Survival (OS) Rate At Different Time Points Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | within 36 months | Overall survival (OS) is defined as the time from randomization to the date of death. The rate of OS (percentage of participants still alive) was determined only in the tivantinib 120 mg BID cohort. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy (ITT Population) | within 10 months | Progression-free survival (PFS) is defined as the time from the date of randomization to the date of the first radiographic disease progression or death due to any cause. The rate of PFS (percentage of participants still alive without disease progression) was determined only in the tivantinib 120 mg BID cohort. |
| Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Baseline to 30 days after last dose, up to approximately 4 years | Treatment-emergent adverse events (TEAEs) are reported for the tivantinib 120 mg BID cohort group. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, France, Germany, Italy, Netherlands, New Zealand, Portugal, Spain, Sweden, Switzerland, United States
Participant flow
Recruitment details
A total of 383 participants who met all inclusion criteria and no exclusion criteria were randomized to treatment. One participant in the tivantinib 120 mg BID cohort was randomized but did not receive treatment.
Pre-assignment details
Eligible participants were randomly assigned on a 2:1 basis to either tivantinib or placebo. Initially, the tivantinib dosage of 240 mg was selected on the basis of efficacy and tolerability established in Phase 1 and Phase 2 studies.
Participants by arm
| Arm | Count |
|---|---|
| Tivantinib 240 mg BID Cohort Participants who received tivantinib 240 mg tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food, for a total daily dose of 480 mg. | 28 |
| Placebo Matching 240 mg BID Cohort Participants who received matching placebo tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food. | 15 |
| Tivantinib 120 mg BID Cohort Participants who received tivantinib 120 mg tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food, for a total daily dose of 240 mg (amended dosing group; primary analysis group). | 225 |
| Placebo Matching 120 mg BID Cohort Participants who received matching placebo tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food. | 114 |
| Total | 382 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 0 | 28 | 11 |
| Overall Study | Clinical Disease Progression | 4 | 2 | 29 | 20 |
| Overall Study | Death | 1 | 2 | 15 | 4 |
| Overall Study | Ongoing Treatment as of 06 Jan 2017 | 0 | 0 | 5 | 2 |
| Overall Study | Other | 0 | 0 | 2 | 3 |
| Overall Study | Progressive Disease | 8 | 7 | 91 | 43 |
| Overall Study | Radiographic Disease Progression | 9 | 4 | 44 | 27 |
| Overall Study | Subject Decision | 0 | 0 | 10 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Total | Tivantinib 240 mg BID Cohort | Placebo Matching 240 mg BID Cohort | Tivantinib 120 mg BID Cohort | Placebo Matching 120 mg BID Cohort |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 218 Participants | 17 Participants | 10 Participants | 127 Participants | 64 Participants |
| Age, Categorical Between 18 and 65 years | 164 Participants | 11 Participants | 5 Participants | 98 Participants | 50 Participants |
| Age, Continuous | 64.8 years STANDARD_DEVIATION 7.8 | 66.6 years STANDARD_DEVIATION 9.3 | 64.9 years STANDARD_DEVIATION 7.4 | 65.6 years STANDARD_DEVIATION 10.2 | 64.7 years STANDARD_DEVIATION 10.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 16 Participants | 1 Participants | 0 Participants | 8 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 0 Participants | 0 Participants | 11 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 63 Participants | 0 Participants | 0 Participants | 43 Participants | 20 Participants |
| Race (NIH/OMB) White | 289 Participants | 27 Participants | 15 Participants | 161 Participants | 86 Participants |
| Sex: Female, Male Female | 38 Participants | 4 Participants | 0 Participants | 27 Participants | 7 Participants |
| Sex: Female, Male Male | 344 Participants | 24 Participants | 15 Participants | 198 Participants | 107 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 28 / 28 | 14 / 15 | 180 / 225 | 94 / 114 |
| other Total, other adverse events | 17 / 28 | 10 / 15 | 214 / 225 | 108 / 114 |
| serious Total, serious adverse events | 17 / 28 | 10 / 15 | 103 / 225 | 51 / 114 |
Outcome results
Primary
Median Overall Survival (OS) Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy
Overall survival (OS) is defined as the time from randomization to the date of death. The rate of OS (percentage of participants still alive) was determined only in the tivantinib 120 mg BID cohort.
Time frame: within 36 months
Population: Overall survival was assessed in the Intent-to-Treat Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tivantinib 120 mg BID Cohort | Median Overall Survival (OS) Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | 8.4 months |
| Placebo Matching 120 mg BID Cohort | Median Overall Survival (OS) Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | 9.1 months |
p-value: 0.8006Log Rank
p-value: 0.806195% CI: [0.7483, 1.2529]Regression, Cox
Primary
Overall Survival (OS) Rate At Different Time Points Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy
Overall survival (OS) is defined as the time from randomization to the date of death. The rate of OS (percentage of participants still alive) was determined only in the tivantinib 120 mg BID cohort.
Time frame: within 36 months
Population: Overall survival was assessed in the Intent-to-Treat Analysis Set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tivantinib 120 mg BID Cohort | Overall Survival (OS) Rate At Different Time Points Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Overall survival at 3 months | 86.6 percentage of participants still alive |
| Tivantinib 120 mg BID Cohort | Overall Survival (OS) Rate At Different Time Points Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Overall survival at 6 months | 61.2 percentage of participants still alive |
| Tivantinib 120 mg BID Cohort | Overall Survival (OS) Rate At Different Time Points Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Overall survival at 9 months | 46.9 percentage of participants still alive |
| Tivantinib 120 mg BID Cohort | Overall Survival (OS) Rate At Different Time Points Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Overall survival at 12 months | 36.6 percentage of participants still alive |
| Tivantinib 120 mg BID Cohort | Overall Survival (OS) Rate At Different Time Points Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Overall survival at 18 months | 25.1 percentage of participants still alive |
| Tivantinib 120 mg BID Cohort | Overall Survival (OS) Rate At Different Time Points Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Overall survival at 24 months | 16.2 percentage of participants still alive |
| Placebo Matching 120 mg BID Cohort | Overall Survival (OS) Rate At Different Time Points Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Overall survival at 18 months | 21.9 percentage of participants still alive |
| Placebo Matching 120 mg BID Cohort | Overall Survival (OS) Rate At Different Time Points Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Overall survival at 3 months | 85.9 percentage of participants still alive |
| Placebo Matching 120 mg BID Cohort | Overall Survival (OS) Rate At Different Time Points Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Overall survival at 12 months | 38.0 percentage of participants still alive |
| Placebo Matching 120 mg BID Cohort | Overall Survival (OS) Rate At Different Time Points Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Overall survival at 6 months | 70.8 percentage of participants still alive |
| Placebo Matching 120 mg BID Cohort | Overall Survival (OS) Rate At Different Time Points Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Overall survival at 24 months | 12.2 percentage of participants still alive |
| Placebo Matching 120 mg BID Cohort | Overall Survival (OS) Rate At Different Time Points Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Overall survival at 9 months | 50.5 percentage of participants still alive |
Secondary
Progression-free Survival Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy (ITT Population)
Progression-free survival (PFS) is defined as the time from the date of randomization to the date of the first radiographic disease progression or death due to any cause. The rate of PFS (percentage of participants still alive without disease progression) was determined only in the tivantinib 120 mg BID cohort.
Time frame: within 10 months
Population: PFS was assessed in the Intent-to-Treat Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tivantinib 120 mg BID Cohort | Progression-free Survival Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy (ITT Population) | 2.1 months |
| Placebo Matching 120 mg BID Cohort | Progression-free Survival Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy (ITT Population) | 2.0 months |
p-value: 0.7509Log Rank
p-value: 0.71695% CI: [0.7487, 1.22]Regression, Cox
Secondary
Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy
Treatment-emergent adverse events (TEAEs) are reported for the tivantinib 120 mg BID cohort group.
Time frame: Baseline to 30 days after last dose, up to approximately 4 years
Population: TEAEs were assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Any TEAEs | 214 Participants |
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Gastrointestinal Disorders | 159 Participants |
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | General Disorders & Administration Site Conditions | 146 Participants |
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Musculoskeletal and Connective Tissue Disorders | 75 Participants |
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Respiratory, Thoracic, and Mediastinal Disorders | 70 Participants |
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Metabolism and Nutrition Disorders | 65 Participants |
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Blood and Lymphatic System Disorders | 64 Participants |
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Nervous System Disorders | 60 Participants |
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Infections and Infestations | 58 Participants |
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Skin and Subcutaneous Tissue Disorders | 57 Participants |
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Investigations | 55 Participants |
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Cardiac Disorders | 52 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Investigations | 36 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Any TEAEs | 108 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Blood and Lymphatic System Disorders | 27 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Gastrointestinal Disorders | 84 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Skin and Subcutaneous Tissue Disorders | 38 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | General Disorders & Administration Site Conditions | 75 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Nervous System Disorders | 27 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Musculoskeletal and Connective Tissue Disorders | 34 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Cardiac Disorders | 13 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Respiratory, Thoracic, and Mediastinal Disorders | 32 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Infections and Infestations | 33 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Metabolism and Nutrition Disorders | 30 Participants |
Secondary
Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy
Treatment-emergent adverse events (TEAEs) are reported for the tivantinib 240 mg BID cohort group.
Time frame: Baseline to 30 days after last dose, up to approximately 4 years
Population: TEAEs were assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Any TEAEs | 28 Participants |
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Blood and Lymphatic System Disorders | 20 Participants |
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Gastrointestinal Disorders | 20 Participants |
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | General Disorders & Administration Site Conditions | 19 Participants |
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Investigations | 11 Participants |
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Respiratory, Thoracic, and Mediastinal Disorders | 8 Participants |
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Infections and Infestations | 7 Participants |
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Skin and Subcutaneous Tissue Disorders | 7 Participants |
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Cardiac Disorders | 7 Participants |
| Tivantinib 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Metabolism and Nutrition Disorders | 6 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Skin and Subcutaneous Tissue Disorders | 3 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Any TEAEs | 14 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Respiratory, Thoracic, and Mediastinal Disorders | 4 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Blood and Lymphatic System Disorders | 4 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Metabolism and Nutrition Disorders | 5 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Gastrointestinal Disorders | 12 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Infections and Infestations | 3 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | General Disorders & Administration Site Conditions | 9 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Cardiac Disorders | 0 Participants |
| Placebo Matching 120 mg BID Cohort | Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy | Investigations | 8 Participants |