Overview
Efficacy, Safety, and Pharmacokinetic of MSC2156119J in Asian Participants With Hepatocellular Carcinoma
Status:
Completed
Completed
Trial end date:
2020-12-03
2020-12-03
Target enrollment:
0
0
Participant gender:
All
All
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.Phase:
Phase 1/Phase 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
Merck KGaA
Merck KGaA, Darmstadt, GermanyTreatments:
Niacinamide
Sorafenib
Tepotinib
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