Efficacy, Safety, and Pharmacokinetic of MSC2156119J in Asian Participants With Hepatocellular Carcinoma

A Multicenter, Randomized, Phase Ib/II Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of MSC2156119J as Monotherapy Versus Sorafenib in Asian Subjects With MET+ Advanced Hepatocellular Carcinoma and Child-Pugh Class A Liver Function

This is an open-label, integrated, Phase 1b/2 trial to determine the recommended Phase 2 dose (RP2D) and to evaluate the efficacy, safety, and pharmacokinetic of MSC2156119J as first-line treatment versus sorafenib in subjects with MET+, Barcelona Clinic Liver Cancer (BCLC) Stage C, systemic treatment naive advanced hepatocellular carcinoma (HCC) and Child-Pugh class A liver function.

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