Patient case: 68-year-old male with non-small cell carcinoma; genetic feature: MET

Clinical trial: Efficacy, Safety, and Pharmacokinetic of MSC2156119J in Asian Subjects With Hepatocellular Carcinoma

Summary: 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.


Eligibility: Inclusion Criteria:
  -  Histologically or cytologically confirmed HCC
  -  Subjects with advanced HCC of BCLC Stage C
  -  Subjects who have disease progression on or are intolerant to the prior standard treatment for advanced HCC (phase Ib Korean subjects only)
  -  A tumor biopsy is required for determining MET status
  -  MET+ status (Phase 2 only), as determined by the central laboratory (Phase 1b retrospectively, Phase 2 for subject selection) as 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, as assessed by investigators according to the Package Insert and clinical judgment (Phase 2 only)
  -  Signed and dated informed consent indicating that the subject has 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 judged by the investigator of at least 3 months
  Exclusion Criteria:
  -  Prior systemic anticancer treatment for advanced HCC, including 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 as 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 as defined in the protocol
  -  Hypertension uncontrolled by standard therapies
  -  Subject 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
  -  Subjects who have 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 subjects only)
  -  Known or suspected drug hypersensitivity to any ingredients of sorafenib (Phase 2 only) and MSC2156119J
  -  Female subjects who are 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)
  -  Subjects with any concurrent medical condition or disease that will potentially compromise the conduction of the study at the discretion of the investigators

Relevance to patient case: not relevant