efficacy, safety, and pharmacokinetic of msc2156119j in asian participants with hepatocellular carcinoma

Conditions: Carcinoma, Hepatocellular

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 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

Keywords: carcinoma, hepatocellular msc2156119j sorafenib recommended phase 2 dose