Clinical trial NCT01988493 (phase 1/phase 2, status: active, not recruiting)
Conditions: carcinoma, hepatocellular
ICD codes: C22.0, C4A.9, C7B.1, C4A.0, C4A.31, C4A.51, C4A.8
Drugs: tepotinib 300 mg, tepotinib 500 mg, tepotinib 1000 mg, tepotinib, sorafenib
SMILES: CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1
Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed HCC

          -  Participants were either intermediate HCC of BCLC Stage B, who were not eligible for
             surgical and/or local-regional therapies or who had progressive disease (PD) after
             surgical and/or local-regional therapies (note: the local-regional therapy must not
             contain sorafenib), or advanced HCC of BCLC Stage C

          -  Participants who had disease progression on or were intolerant to the prior standard
             treatment for advanced HCC (phase Ib Korean subjects only)

          -  A tumor biopsy was required for determining MET status

          -  MET+ status (Phase 2 only), as determined by the central laboratory (Phase 1b
             retrospectively, Phase 2 for participant selection) were defined in the protocol

          -  Child-Pugh class A with no encephalopathy according to the screening assessment

          -  Asian male or female, 18 years of age or older

          -  Measurable disease in accordance with RECIST v1.1 (Phase 2 only)

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2

          -  Eligible for treatment with sorafenib, was assessed by investigators according to the
             Package Insert and clinical judgment (Phase 2 only)

          -  Signed and dated informed consent indicating that the participants had been informed
             of all the pertinent aspects of the trial prior to enrollment

          -  Willingness and ability to comply with scheduled visits, treatment plans, laboratory
             tests, and other trial procedures

          -  Life expectancy was judged by the investigator of at least 3 months

        Exclusion Criteria:

          -  Prior systemic anticancer treatment for advanced HCC, included targeted therapy (for
             example, sorafenib), chemotherapy, or any other investigational agent (Phase 2 only)

          -  Prior treatment with any agent targeting the hepatocyte growth factor (HGF)/c-Met
             pathway

          -  Prior local-regional therapy within 4 weeks prior to Day 1 of trial treatment

          -  Prior history of liver transplant

          -  Laboratory index at baseline were defined in the protocol

          -  Past or current history of neoplasm other than HCC, except for curatively treated
             non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively
             treated and with no evidence of disease for at least 5 years

          -  Known central nervous system (CNS) or brain metastasis that is either symptomatic or
             untreated

          -  Medical history of difficulty swallowing, malabsorption, or other chronic
             gastrointestinal disease, or conditions that may hamper compliance and/or absorption
             of the tested products

          -  Clinically significant gastrointestinal bleeding within 4 weeks before trial entry

          -  Peripheral neuropathy Grade greater than or equal to 2 (Common Terminology Criteria
             for Adverse Events [CTCAE] v4.0)

          -  Impaired cardiac function was defined in the protocol

          -  Hypertension uncontrolled by standard therapies

          -  Participants with a family history of long QT syndrome or who take any agent that is
             known to prolong QT/QTc interval

          -  Known human immunodeficiency virus (HIV) infection

          -  Particpants who had acute pancreatitis and/or chronic pancreatitis, with elevated
             lipase and/or amylase, clinical symptoms, and/or imaging studies that are indicative
             of the diagnosis (Mainland Chinese participants only)

          -  Known or suspected drug hypersensitivity to any ingredients of sorafenib (Phase 2
             only) and MSC2156119J

          -  Female participants who were pregnant or lactating, or males and females of
             reproductive potential not willing or not able to employ a highly effective method of
             birth control/contraception to prevent pregnancy from 2 weeks before receiving study
             drug until 3 months after receiving the last dose of study drug

          -  Concurrent treatment with a non-permitted drug

          -  Substance abuse, other acute or chronic medical or psychiatric condition, or
             laboratory abnormalities that may increase the risk associated with trial
             participation in the opinion of the investigator

          -  Participation in another clinical trial within the past 28 days

          -  Previous anticancer treatment-related toxicities not recovered to baseline or Grade
             0-1 (except alopecia and peripheral neuropathy)

          -  Participants with any concurrent medical condition or disease that will potentially
             compromise the conduct of the study at the discretion of the investigators