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

• ClinicalTrials.gov Identifier: NCT01988493
• Recruitment Status: Completed
• First Posted: November 20, 2013
• Results First Posted: July 24, 2019
• Last Update Posted: August 24, 2022
• Sponsor: Merck KGaA, Darmstadt, Germany
• Information provided by (Responsible Party): Merck KGaA, Darmstadt, Germany

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Carcinoma, Hepatocellular	Drug: Tepotinib 300 mg; Drug: Tepotinib 500 mg; Drug: Tepotinib 1000 mg; Drug: Tepotinib; Drug: Sorafenib	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 117 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 6, 2014
• Actual Primary Completion Date: February 5, 2018
• Actual Study Completion Date: December 3, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Phase 1b: Tepotinib 300 mg; Participants received Tepotinib 300 milligram (mg) orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.	Drug: Tepotinib 300 mg; Participants received Tepotinib 300 milligram (mg) orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.
Experimental: Phase 1b: Tepotinib 500 mg; Participants received Tepotinib 500 mg orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.	Drug: Tepotinib 500 mg; Participants received Tepotinib 500 mg orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.
Experimental: Phase 1b: Tepotinib 1000 mg; Participants received Tepotinib 1000 mg orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.	Drug: Tepotinib 1000 mg; Participants received Tepotinib 1000 mg orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal
Experimental: Phase 2: Tepotinib; Participants randomized to receive Tepotinib recommended Phase 2 dose (RP2D) determined from Phase 1b over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.	Drug: Tepotinib; Participants randomized to receive Tepotinib recommended Phase 2 dose (RP2D) determined from Phase 1b over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.
Experimental: Phase 2 Sorafenib; Participants randomized to receive Sorafenib 400 mg orally twice daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.	Drug: Sorafenib; Participants randomized to receive Sorafenib 400 mg orally twice daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.

Outcome Measures

Primary Outcome Measures :

1. Phase 1b: Number of Participants Experiencing Dose Limiting Toxicity [ Time Frame: Day 1 to Day 21 of Cycle 1 (each cycle is 21 days) ]
   Dose limiting toxicity (DLT) was defined as toxicities at any dose level and judged to be related to the study treatment by investigator and/or the sponsor. DLTs included Grade 4 neutropenia for more than 7 days; Grade greater than or equal to (>=) 3 febrile neutropenia for more than 1 day; Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with non-traumatic bleeding; Grade >= 3 uncontrolled nausea/vomiting and/or diarrhea despite adequate and optimal treatment and Grade >= 3 any non-hematological adverse event (AE), except the aforementioned gastrointestinal events and alopecia. Number of participants who experienced DLT during phase 1b were reported.
2. Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs [ Time Frame: Baseline up to Day 30 after the last dose of study treatment, assessed up to 94 weeks ]
   An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug and assessed up to 94 weeks. TEAEs include both Serious TEAEs and non-serious TEAEs.
3. Phase 2: Time to Progression (TTP) Based on Tumor Assessment by an Independent Review Committee (IRC) [ Time Frame: From randomization to date of the observation of radiological progressive disease, assessed up to maximum 3.8 years ]
   TTP was defined as the time in months from randomization to date of the observation of radiological progressive disease (PD) (based on Response Evaluation Criteria in Solid Tumors [RECIST] v1.1) assessed by an IRC. PD is defined as at least 20 percent (%) increase in sum of diameters of target lesions, taking as reference as smallest sum on study; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must demonstrate an absolute increase of at least 5 millimeter (mm).

Secondary Outcome Measures :

1. Phase 2: Progression Free Survival (PFS) Time Based on Tumor Assessment by the Independent Review Committee (IRC) [ Time Frame: Up to 2.8 years ]
   Progression-free survival (PFS) time was defined as the time in months from randomization to either first observation of disease progression (based on RECIST v1.1) or occurrence of death due to any cause within 84 days of either randomization or the last tumor assessment. PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 millimeter(mm). PFS was measured using Kaplan-Meier (KM) estimates.
2. Phase 2: Overall Survival (OS) [ Time Frame: Time from randomization to the date of death or up to 6.9 years ]
   Overall survival time was measured as time in months between the date of randomization and the date of death.
3. Phase 2: Time to Progression (TTP) Based on Tumor Assessment by Investigator [ Time Frame: From randomization to date of the observation of radiological progressive disease, assessed up to maximum 2.8 years ]
   TTP was defined as the time in months from randomization to date of the observation of radiological PD (based on RECIST v1.1) assessed by the investigator. PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm.
4. Phase 1b: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-infinity) of Tepotinib [ Time Frame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 1 and Day 15 of Cycle 1 (each Cycle is 21 days) ]
   The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
5. Phase 1b: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Tepotinib [ Time Frame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 1 and Day 15 of Cycle 1 (each Cycle is 21 days) ]
   Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration is at or above the lower limit of quantification (LLLQ). AUC(0-t) was calculated according to the mixed log-linear trapezoidal rule.
6. Phase 1b: Area Under the Plasma Concentration-Time Curve Within 1 Dosing Interval (AUC 0-tau) of Tepotinib [ Time Frame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 1 and Day 15 of Cycle 1 (each Cycle is 21 days) ]
   AUC (0-tau) is the area under the plasma concentration time curve within 1 dosing interval.
7. Phase 1b: Maximum Observed Plasma Concentration (Cmax) of Tepotinib [ Time Frame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 1 and Day 15 of Cycle 1 (each Cycle is 21 days) ]
   Cmax is the maximum observed plasma concentration obtained directly from the concentration versus time curve.
8. Phase 1b: Minimum Observed Plasma Concentration (Cmin) of Tepotinib [ Time Frame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 15 of Cycle 1 (each Cycle is 21 days) ]
   Cmin is minimum observed plasma concentration obtained directly from the concentration versus time curve.
9. Phase 1b: Average Observed Plasma Concentration (Cav) of Tepotinib [ Time Frame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 15 of Cycle 1 (each Cycle is 21 days) ]
   Cavg is the average plasma concentration within 1 dosing interval obtained directly from the concentration versus time curve.
10. Phase 1b: Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib [ Time Frame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 1 and Day 15 of Cycle 1 (each Cycle is 21 days) ]
    Tmax is time to reach maximum observed plasma concentration obtained directly from the concentration versus time curve.
11. Phase 1b: Apparent Volume of Distribution During the Terminal Phase (Vz/f) of Tepotinib [ Time Frame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 1 and Day 15 of Cycle 1 (each Cycle is 21 days) ]
    The Vz/f was defined as the theoretical volume in which the total amount of required to uniformly distribute to produce the desired plasma concentration. Apparent volume of distribution after oral dose (Vz/F) was influenced by the fraction absorbed. The Vz/f was calculated by dividing the dose with area under the concentration time curve from time zero to infinity multiplied with terminal elimination rate constant Lambda(z). Vz/f=Dose/AUC(0-inf)* Lambda(z).
12. Phase 1b: Apparent Total Body Clearance From Plasma (CL/f) of Tepotinib [ Time Frame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 1 and Day 15 of Cycle 1 (each Cycle is 21 days) ]
    The CL/f is a measure of the rate at which it was metabolized or eliminated by normal biological processes. Clearance obtained after oral dose was influenced by the fraction of the dose absorbed. The CL/F from plasma was calculated using the formula: Dose divided by area under the concentration time curve from time zero to infinity (AUC0-inf).
13. Phase 1b: Apparent Volume of Distribution During the Steady State (Vss/f) of Tepotinib [ Time Frame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 1 and Day 15 of Cycle 1 (each Cycle is 21 days) ]
    Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss/f after oral dose was influenced by the fraction absorbed.
14. Phase 1b: Apparent Terminal Elimination Rate Constant Lambda(z) of Tepotinib [ Time Frame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 1 and Day 15 of Cycle 1 (each Cycle is 21 days) ]
    Lambda(z) was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
15. Phase 1b: Apparent Terminal Half-life (t1/2) of Tepotinib [ Time Frame: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 1 and Day 15 of Cycle 1 (each Cycle is 21 days) ]
    Apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination.
16. Phase 2: Time-to-Symptomatic Progression (TTSP) [ Time Frame: Up to 6.9 years ]
    Time-to-symptomatic progression was defined as time (in months) from first study drug administration to the date of deterioration of symptoms assessed by Functional Assessment of Cancer Therapy Hepatobiliary Symptom Index 8 (FHSI-8) (defined as at least a 4-point increase, i.e., higher score, compared with baseline value), or deterioration to Eastern Cooperative Oncology Group (ECOG) performance score 4, or death. FHSI-8 assesses hepatobiliary cancer symptoms with total score ranges from 0 to 32 (0 = the best quality of life; 32 = the worst quality of life with severe symptoms). ECOG assess participant's performance status on a scale of 0 to 5, where 0=fully active and 5=dead.
17. Phase 2: Objective Response Rate (ORR) Based on Tumor Assessment by the IRC [ Time Frame: Time from randomization until the first occurrence of PD assessed up to 6.9 years ]
    The objective response rate (ORR) was defined as the percentage of participants who had achieved complete response (CR) or partial response (PR) as the best overall response according to radiological assessments as adjudicated by the IRC from randomization until the first occurrence of PD. CR: Complete Response (CR) defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial response (PR) defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started.
18. Phase 2: Percentage of Participants With Disease Control Based on Tumor Assessment by IRC According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria [ Time Frame: Time from randomization until the first occurrence of PD assessed up to 6.9 years ]
    Disease control was defined as CR, PR, or stable disease (SD) as the best overall response according to radiological assessments as adjudicated by the IRC from randomization until the first occurrence of PD. CR defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD was defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started. Percentage of participants with disease control were reported.
19. Phase 2: Progression-free Survival (PFS) Based on Tumor Assessment by the Investigator [ Time Frame: Time from randomization to disease progression or occurrence of death due to any cause within 84 days of either randomization or the last tumor assessment, assessed up to 6.9 years ]
    Progression-free survival (assessed by the Investigator) time was defined as the time in months from randomization to either first observation of radiologically confirmed progression disease by the investigator or occurrence of death due to any cause within 84 days of either randomization or the last tumor assessment. PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm. PFS was measured using Kaplan-Meier (KM) estimates.
20. Phase 2: Objective Response Rate (ORR) Based on Tumor Assessment by the Investigator [ Time Frame: Time from randomization until the first occurrence of PD assessed up to 6.9 years ]
    The objective response rate was defined as the percentage of participants who had achieved CR or PR as the best overall response according to radiological assessments as adjudicated by the investigator from randomization until the first occurrence of PD. CR defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD was defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started.
21. Phase 2: Percentage of Participants With Disease Control Based on Tumor Assessment by Investigator According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria [ Time Frame: Approximately up to 6.9 years ]
    Disease control was defined as CR, PR, or stable disease (SD) as the best overall response according to radiological assessments as adjudicated by the IRC from randomization until the first occurrence of PD. CR defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD was defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started. Percentage of participants with disease control were reported.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

China, Beijing

307 Hosptial of PLA

Beijing, Beijing, China, 100071

Peking University Cancer Hospital

Beijing, Beijing, China, 100142

China, Fujian

Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA

Fuzhou, Fujian, China, 350025

China, Guangdong

Sun Yat-sen University, Cancer Center

Guangzhou, Guangdong, China, 510060

Nanfang Hospital

Guangzhou, Guangdong, China, 510515

China, Heilongjiang

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China, 150081

China, Hunan

The Third Xiangya Hospital of Central South University

Changsha, Hunan, China, 410013

China, Jiangsu

Nanjing Bayi Hospital

Nanjing, Jiangsu, China, 210002

Nanjing First Hospital Affiliated to Nanjing Medical University

Nanjing, Jiangsu, China, 210029

China, Jilin

Jilin Cancer Hospital

Changchun, Jilin, China, 130012

China, Shanghai

Shanghai Cancer Hospital, Fudan University

Shanghai, Shanghai, China, 200032

Zhongshan Hospital Fudan University

Shanghai, Shanghai, China, 200032

China, Zhejiang

Cancer Hospital, Tianjin Medical University

Tianjin, Zhejiang, China, 300060

Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine

Zhejiang, Zhejiang, China, 310016

China

Beijing Friendship Hospital, Capital Medical University

Beijing, China, 100050

Korea, Republic of

Dong-A University Hospital

Busan, Korea, Republic of, 602-715

Pusan National University Hospital

Busan, Korea, Republic of, 602-739

Keimyung University Dongsan Hospital

Daegu, Korea, Republic of, 41931

Kyungpook National University Hospital

Daegu, Korea, Republic of, 700-721

National Cancer Center

Goyang-si, Korea, Republic of, 10408

CHA Bundang Medical Center, CHA University

Seongnam-si,, Korea, Republic of, 13496

Seoul National University Bundang Hospital

Seongnam-si, Korea, Republic of, 13620

Kyung Hee University Hospital

Seoul, Korea, Republic of, 02447

Korea University Anam Hospital

Seoul, Korea, Republic of, 02841

Severance Hospital, Yonsei University

Seoul, Korea, Republic of, 03722

Asan Medical Center

Seoul, Korea, Republic of, 05505

Gangnam Severance Hospital, Yonsei University Health System

Seoul, Korea, Republic of, 06273

Samsung Medical Center

Seoul, Korea, Republic of, 06351

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, Korea, Republic of, 06591

Korea University Guro Hospital

Seoul, Korea, Republic of, 08308

Seoul National University Hospital

Seoul, Korea, Republic of, 110744

Ajou University Hospital

Suwon-si, Korea, Republic of, 443-380

Pusan National University Yangsan Hospital

Yangsan, Korea, Republic of, 626-770

Taiwan

Changhua Christian Hospital

Changhua, Taiwan, 50004

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung, Taiwan, 807

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung, Taiwan, 83301

Taichung Veterans General Hospital

Taichung, Taiwan, 40705

National Cheng Kung University Hospital

Tainan, Taiwan, 704

Chi Mei Medical Center, Liou Ying

Tainan, Taiwan, 736

National Taiwan University Hospital

Taipei, Taiwan, 100

Mackay Memorial Hospital

Taipei, Taiwan, 10449

Taipei Veterans General Hospital

Taipei, Taiwan, 11217

Chang Gung Memorial Hospital, Linkou

Taoyuan, Taiwan, 333

Sponsors and Collaborators

Merck KGaA, Darmstadt, Germany

Investigators

• Study Director: Medical Responsible; Merck KGaA, Darmstadt, Germany

  Study Documents (Full-Text)

Documents provided by Merck KGaA, Darmstadt, Germany:

Study Protocol  [PDF] May 19, 2017

Statistical Analysis Plan  [PDF] February 12, 2018

More Information

Additional Information:

Trial Awareness and Transparency website 

Redacted Clinical study report, redacted clinical study protocol and redacted statistical analysis plan for this study is also available at the HC-PRCI portal (Health Canada-Public release of clinical information) 

Publications of Results:

Ryoo BY, Cheng AL, Ren Z, Kim TY, Pan H, Rau KM, Choi HJ, Park JW, Kim JH, Yen CJ, Lim HY, Zhou D, Straub J, Scheele J, Berghoff K, Qin S. Randomised Phase 1b/2 trial of tepotinib vs sorafenib in Asian patients with advanced hepatocellular carcinoma with MET overexpression. Br J Cancer. 2021 Jul;125(2):200-208. doi: 10.1038/s41416-021-01380-3. Epub 2021 May 10.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Xiong W, Hietala SF, Nyberg J, Papasouliotis O, Johne A, Berghoff K, Goteti K, Dong J, Girard P, Venkatakrishnan K, Strotmann R. Exposure-response analyses for the MET inhibitor tepotinib including patients in the pivotal VISION trial: support for dosage recommendations. Cancer Chemother Pharmacol. 2022 Jul;90(1):53-69. doi: 10.1007/s00280-022-04441-3. Epub 2022 Jun 30.

• Responsible Party: Merck KGaA, Darmstadt, Germany
• ClinicalTrials.gov Identifier: NCT01988493
• Other Study ID Numbers: 200095-004
• First Posted: November 20, 2013
• Results First Posted: July 24, 2019
• Last Update Posted: August 24, 2022
• Last Verified: August 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck KGaA, Darmstadt, Germany:

Carcinoma, Hepatocellular; MSC2156119J; Sorafenib; Recommended Phase 2 dose

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Hepatocellular; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Sorafenib; Tepotinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action