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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1b: Tepotinib 300 mg | Experimental | Participants received Tepotinib 300 milligram (mg) orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal. |
|
| Phase 1b: Tepotinib 500 mg | Experimental | Participants received Tepotinib 500 mg orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal. |
|
| Phase 1b: Tepotinib 1000 mg | Experimental | Participants received Tepotinib 1000 mg orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal. |
|
| Phase 2: Tepotinib | Experimental | 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. |
|
| Phase 2 Sorafenib | Experimental | Participants randomized to receive Sorafenib 400 mg orally twice daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tepotinib 300 mg | Drug | Participants received Tepotinib 300 milligram (mg) orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal. |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1b: Number of Participants Experiencing Dose Limiting Toxicity | 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. | Day 1 to Day 21 of Cycle 1 (each cycle is 21 days) |
| Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | 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. | Baseline up to Day 30 after the last dose of study treatment, assessed up to 94 weeks |
| Phase 2: Time to Progression (TTP) Based on Tumor Assessment by an Independent Review Committee (IRC) | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 2: Progression Free Survival (PFS) Time Based on Tumor Assessment by the Independent Review Committee (IRC) | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 307 Hosptial of PLA | Beijing | Beijing Municipality | 100071 | China | ||
| Peking University Cancer Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33972742 | Result | 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. | |
| 35771259 |
| Label | URL |
|---|---|
| Trial Awareness and Transparency website | View source |
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A total of 27 participants were enrolled in Phase 1b part of the study and a total of 90 participants were enrolled in phase 2 part of the study. Participants enrolled in phase 1b were not eligible for randomization in phase 2.
First participant enrolled 06 Jan 2014. Last participant last visit: 03 Dec 2020.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | Phase 1b: Tepotinib 500 mg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 19, 2017 | Feb 5, 2019 |
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|
| Tepotinib 500 mg | Drug | Participants received Tepotinib 500 mg orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal. |
|
| Tepotinib 1000 mg | Drug | Participants received Tepotinib 1000 mg orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal |
|
| Tepotinib | Drug | 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. |
|
| Sorafenib | Drug | Participants randomized to receive Sorafenib 400 mg orally twice daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal. |
|
| From randomization to date of the observation of radiological progressive disease, assessed up to maximum 3.8 years |
| Up to 2.8 years |
| Phase 2: Overall Survival (OS) | Overall survival time was measured as time in months between the date of randomization and the date of death. | Time from randomization to the date of death or up to 6.9 years |
| Phase 2: Time to Progression (TTP) Based on Tumor Assessment by Investigator | 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. | From randomization to date of the observation of radiological progressive disease, assessed up to maximum 2.8 years |
| Phase 1b: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-infinity) of Tepotinib | The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. | 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) |
| Phase 1b: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Tepotinib | 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. | 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) |
| Phase 1b: Area Under the Plasma Concentration-Time Curve Within 1 Dosing Interval (AUC 0-tau) of Tepotinib | AUC (0-tau) is the area under the plasma concentration time curve within 1 dosing interval. | 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) |
| Phase 1b: Maximum Observed Plasma Concentration (Cmax) of Tepotinib | Cmax is the maximum observed plasma concentration obtained directly from the concentration versus time curve. | 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) |
| Phase 1b: Minimum Observed Plasma Concentration (Cmin) of Tepotinib | Cmin is minimum observed plasma concentration obtained directly from the concentration versus time curve. | 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) |
| Phase 1b: Average Observed Plasma Concentration (Cav) of Tepotinib | Cavg is the average plasma concentration within 1 dosing interval obtained directly from the concentration versus time curve. | 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) |
| Phase 1b: Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib | Tmax is time to reach maximum observed plasma concentration obtained directly from the concentration versus time curve. | 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) |
| Phase 1b: Apparent Volume of Distribution During the Terminal Phase (Vz/f) of Tepotinib | 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). | 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) |
| Phase 1b: Apparent Total Body Clearance From Plasma (CL/f) of Tepotinib | 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). | 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) |
| Phase 1b: Apparent Volume of Distribution During the Steady State (Vss/f) of Tepotinib | 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. | 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) |
| Phase 1b: Apparent Terminal Elimination Rate Constant Lambda(z) of Tepotinib | Lambda(z) was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. | 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) |
| Phase 1b: Apparent Terminal Half-life (t1/2) of Tepotinib | 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. | 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) |
| Phase 2: Time-to-Symptomatic Progression (TTSP) | 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. | Up to 6.9 years |
| Phase 2: Objective Response Rate (ORR) Based on Tumor Assessment by the IRC | 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. | Time from randomization until the first occurrence of PD assessed up to 6.9 years |
| 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 | 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. | Time from randomization until the first occurrence of PD assessed up to 6.9 years |
| Phase 2: Progression-free Survival (PFS) Based on Tumor Assessment by the Investigator | 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. | 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 |
| Phase 2: Objective Response Rate (ORR) Based on Tumor Assessment by the Investigator | 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. | Time from randomization until the first occurrence of PD assessed up to 6.9 years |
| 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 | 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. | Approximately up to 6.9 years |
| Beijing |
| Beijing Municipality |
| 100142 |
| China |
| Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA | Fuzhou | Fujian | 350025 | China |
| Sun Yat-sen University, Cancer Center | Guangzhou | Guangdong | 510060 | China |
| Nanfang Hospital | Guangzhou | Guangdong | 510515 | China |
| Harbin Medical University Cancer Hospital | Harbin | Heilongjiang | 150081 | China |
| The Third Xiangya Hospital of Central South University | Changsha | Hu'nan | 410013 | China |
| Nanjing Bayi Hospital | Nanjing | Jiangsu | 210002 | China |
| Nanjing First Hospital Affiliated to Nanjing Medical University | Nanjing | Jiangsu | 210029 | China |
| Jilin Cancer Hospital | Changchun | Jilin | 130012 | China |
| Shanghai Cancer Hospital, Fudan University | Shanghai | Shanghai Municipality | 200032 | China |
| Zhongshan Hospital Fudan University | Shanghai | Shanghai Municipality | 200032 | China |
| Cancer Hospital, Tianjin Medical University | Tianjin | Zhejiang | 300060 | China |
| Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine | Zhejiang | Zhejiang | 310016 | China |
| Beijing Friendship Hospital, Capital Medical University | Beijing | 100050 | China |
| Dong-A University Hospital | Busan | 602-715 | South Korea |
| Pusan National University Hospital | Busan | 602-739 | South Korea |
| Keimyung University Dongsan Hospital | Daegu | 41931 | South Korea |
| Kyungpook National University Hospital | Daegu | 700-721 | South Korea |
| National Cancer Center | Goyang-si | 10408 | South Korea |
| CHA Bundang Medical Center, CHA University | Seongnam-si | 13496 | South Korea |
| Seoul National University Bundang Hospital | Seongnam-si | 13620 | South Korea |
| Kyung Hee University Hospital | Seoul | 02447 | South Korea |
| Korea University Anam Hospital | Seoul | 02841 | South Korea |
| Severance Hospital, Yonsei University | Seoul | 03722 | South Korea |
| Asan Medical Center | Seoul | 05505 | South Korea |
| Gangnam Severance Hospital, Yonsei University Health System | Seoul | 06273 | South Korea |
| Samsung Medical Center | Seoul | 06351 | South Korea |
| The Catholic University of Korea, Seoul St. Mary's Hospital | Seoul | 06591 | South Korea |
| Korea University Guro Hospital | Seoul | 08308 | South Korea |
| Seoul National University Hospital | Seoul | 110744 | South Korea |
| Ajou University Hospital | Suwon | 443-380 | South Korea |
| Pusan National University Yangsan Hospital | Yangsan | 626-770 | South Korea |
| Changhua Christian Hospital | Changhua | 50004 | Taiwan |
| Kaohsiung Medical University Chung-Ho Memorial Hospital | Kaohsiung City | 807 | Taiwan |
| Kaohsiung Chang Gung Memorial Hospital | Kaohsiung City | 83301 | Taiwan |
| Taichung Veterans General Hospital | Taichung | 40705 | Taiwan |
| National Cheng Kung University Hospital | Tainan | 704 | Taiwan |
| Chi Mei Medical Center, Liou Ying | Tainan | 736 | Taiwan |
| National Taiwan University Hospital | Taipei | 100 | Taiwan |
| Mackay Memorial Hospital | Taipei | 10449 | Taiwan |
| Taipei Veterans General Hospital | Taipei | 11217 | Taiwan |
| Chang Gung Memorial Hospital, Linkou | Taoyuan | 333 | Taiwan |
| 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. |
| 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) | View source |
Participants received Tepotinib 500 mg orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.
| FG002 | 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. |
| FG003 | 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. |
| FG004 | 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. |
| Treated |
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| Safety Population |
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| COMPLETED |
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| NOT COMPLETED |
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The safety analysis set included all participants who had received any dose of the study medication.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | 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. |
| BG003 | 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. |
| BG004 | 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. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Phase 1b: Number of Participants Experiencing Dose Limiting Toxicity | 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. | Dose Limiting Toxicity (DLT) set included all participants who experienced a DLT during Cycle 1, or received at least 80 percent of all planned doses of treatment during Cycle. | Posted | Count of Participants | Participants | Day 1 to Day 21 of Cycle 1 (each cycle is 21 days) |
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| Primary | Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | 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. | The safety analysis set included all participants who had received any dose of the study medication. | Posted | Count of Participants | Participants | Baseline up to Day 30 after the last dose of study treatment, assessed up to 94 weeks |
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| Primary | Phase 2: Time to Progression (TTP) Based on Tumor Assessment by an Independent Review Committee (IRC) | 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). | The modified intent-to treat (mITT) analysis set in the Phase 2 part of this study included all participants with Mesenchymal-epithelial transition (MET)+ hepatocelluar carcinoma (HCC) who were randomized to study treatment. | Posted | Median | 90% Confidence Interval | Months | From randomization to date of the observation of radiological progressive disease, assessed up to maximum 3.8 years |
| |||||||||||||||||||||||||||||||||
| Secondary | Phase 2: Progression Free Survival (PFS) Time Based on Tumor Assessment by the Independent Review Committee (IRC) | 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. | The mITT analysis set in the Phase 2 part of this study included all participants with MET+ HCC who were randomized to study treatment. | Posted | Median | 90% Confidence Interval | Months | Up to 2.8 years |
| |||||||||||||||||||||||||||||||||
| Secondary | Phase 2: Overall Survival (OS) | Overall survival time was measured as time in months between the date of randomization and the date of death. | The mITT analysis set in the Phase 2 part of this study included all participants with MET+ HCC who were randomized to study treatment. | Posted | Median | 90% Confidence Interval | Months | Time from randomization to the date of death or up to 6.9 years |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Phase 2: Time to Progression (TTP) Based on Tumor Assessment by Investigator | 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. | The mITT analysis set in the Phase 2 part of this study included all participants with MET+ HCC who were randomized to study treatment. | Posted | Median | 90% Confidence Interval | Months | From randomization to date of the observation of radiological progressive disease, assessed up to maximum 2.8 years |
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| Secondary | Phase 1b: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-infinity) of Tepotinib | The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. | The Pharmacokinetic (PK) analysis included all participants who had received at least 1 dose of Tepotinib and who had provided at least 1 plasma concentration measurement of Tepotinib after the first dose. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram hour per milliliter (ng*h/mL) | 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) |
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| Secondary | Phase 1b: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Tepotinib | 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. | The PK analysis set was used. Here, "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable at each specified time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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) |
| |||||||||||||||||||||||||||||||||
| Secondary | Phase 1b: Area Under the Plasma Concentration-Time Curve Within 1 Dosing Interval (AUC 0-tau) of Tepotinib | AUC (0-tau) is the area under the plasma concentration time curve within 1 dosing interval. | The PK analysis set was used. Here, "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable at each specified time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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) |
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| Secondary | Phase 1b: Maximum Observed Plasma Concentration (Cmax) of Tepotinib | Cmax is the maximum observed plasma concentration obtained directly from the concentration versus time curve. | The PK analysis set was used. Here "Number Analyzed" signifies those participants who were evaluable for specified time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
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| Secondary | Phase 1b: Minimum Observed Plasma Concentration (Cmin) of Tepotinib | Cmin is minimum observed plasma concentration obtained directly from the concentration versus time curve. | The PK analysis set was used. Here, "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
| |||||||||||||||||||||||||||||||||
| Secondary | Phase 1b: Average Observed Plasma Concentration (Cav) of Tepotinib | Cavg is the average plasma concentration within 1 dosing interval obtained directly from the concentration versus time curve. | The PK analysis set was used. Here, "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
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| Secondary | Phase 1b: Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib | Tmax is time to reach maximum observed plasma concentration obtained directly from the concentration versus time curve. | The PK analysis set was used. Here "Number Analyzed" signifies those participants who were evaluable for specified time point. | Posted | Median | Full Range | Hours | 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) |
| |||||||||||||||||||||||||||||||||
| Secondary | Phase 1b: Apparent Volume of Distribution During the Terminal Phase (Vz/f) of Tepotinib | 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). | The PK analysis included all participants who had received at least 1 dose of Tepotinib and who had provided at least 1 plasma concentration measurement of Tepotinib after the first dose. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter | 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) |
| |||||||||||||||||||||||||||||||||
| Secondary | Phase 1b: Apparent Total Body Clearance From Plasma (CL/f) of Tepotinib | 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). | The PK analysis included all participants who had received at least 1 dose of Tepotinib and who had provided at least 1 plasma concentration measurement of Tepotinib after the first dose. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter per hour (L/h) | 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) |
| |||||||||||||||||||||||||||||||||
| Secondary | Phase 1b: Apparent Volume of Distribution During the Steady State (Vss/f) of Tepotinib | 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. | The PK analysis included all participants who had received at least 1 dose of Tepotinib and who had provided at least 1 plasma concentration measurement of Tepotinib after the first dose. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter | 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) |
| |||||||||||||||||||||||||||||||||
| Secondary | Phase 1b: Apparent Terminal Elimination Rate Constant Lambda(z) of Tepotinib | Lambda(z) was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. | The PK analysis included all participants who had received at least 1 dose of Tepotinib and who had provided at least 1 plasma concentration measurement of Tepotinib after the first dose. | Posted | Geometric Mean | Geometric Coefficient of Variation | 1 per hour | 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) |
| |||||||||||||||||||||||||||||||||
| Secondary | Phase 1b: Apparent Terminal Half-life (t1/2) of Tepotinib | 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. | The PK analysis included all participants who had received at least 1 dose of Tepotinib and who had provided at least 1 plasma concentration measurement of Tepotinib after the first dose. | Posted | Median | Full Range | Hours | 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) |
| |||||||||||||||||||||||||||||||||
| Secondary | Phase 2: Time-to-Symptomatic Progression (TTSP) | 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. | The mITT analysis set in the Phase 2 part of this study included all participants with MET+ HCC who were randomized to study treatment. As per planned analysis, data for this outcome was analyzed only for phase 2 based on combined analysis of both FHSI-8 and ECOG. | Posted | Median | 90% Confidence Interval | Months | Up to 6.9 years |
| |||||||||||||||||||||||||||||||||
| Secondary | Phase 2: Objective Response Rate (ORR) Based on Tumor Assessment by the IRC | 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. | The mITT analysis set in the Phase 2 part of this study included all participants with MET+ HCC who were randomized to study treatment. | Posted | Number | 90% Confidence Interval | Percentage of participants | Time from randomization until the first occurrence of PD assessed up to 6.9 years |
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| Secondary | 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 | 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. | The mITT analysis set in the Phase 2 part of this study included all participants with MET+ HCC who were randomized to study treatment. | Posted | Number | 90% Confidence Interval | Percentage of participants | Time from randomization until the first occurrence of PD assessed up to 6.9 years |
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| Secondary | Phase 2: Progression-free Survival (PFS) Based on Tumor Assessment by the Investigator | 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. | The mITT analysis set in the Phase 2 part of this study included all participants with MET+ HCC who were randomized to study treatment. | Posted | Median | 90% Confidence Interval | Months | 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 |
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| Secondary | Phase 2: Objective Response Rate (ORR) Based on Tumor Assessment by the Investigator | 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. | The mITT analysis set in the Phase 2 part of this study included all participants with MET+ HCC who were randomized to study treatment. | Posted | Number | 90% Confidence Interval | Percentage of participants | Time from randomization until the first occurrence of PD assessed up to 6.9 years |
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| Secondary | 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 | 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. | The mITT analysis set in the Phase 2 part of this study included all participants with MET+ HCC who were randomized to study treatment. | Posted | Number | 90% Confidence Interval | Percentage of Participants | Approximately up to 6.9 years |
|
Baseline up to Day 30 after the last dose of study treatment, assessed up to 94 weeks (Phase 1b) and 6.9 years (Phase 2).
The safety analysis set included all participants who had received any dose of the study medication.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 7 | 7 | 2 | 7 | 7 | 7 |
| EG001 | 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. | 11 | 14 | 9 | 14 | 14 | 14 |
| EG002 | 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. | 3 | 6 | 4 | 6 | 6 | 6 |
| EG003 | 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. | 24 | 45 | 23 | 45 | 43 | 45 |
| EG004 | 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. | 30 | 44 | 12 | 44 | 43 | 44 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Supraventricular tachycardia | Cardiac disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Duodenal ulcer | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Encapsulating peritoneal sclerosis | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Melaena | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Duodenal ulcer haemorrhage | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Peritoneal haemorrhage | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Disease progression | General disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Hernia | General disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Candida infection | Infections and infestations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Enteritis infectious | Infections and infestations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Gouty arthritis | Musculoskeletal and connective tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Metastases to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Bladder cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Hepatic encephalopathy | Nervous system disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Lymphoedema | Vascular disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Abdominal mass | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Anorectal discomfort | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Gastric ulcer | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Gingival bleeding | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Chest pain | General disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Disease progression | General disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Localised oedema | General disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Malaise | General disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Oedema | General disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Hepatorenal syndrome | Hepatobiliary disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Rash pustular | Infections and infestations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Creatinine renal clearance decreased | Investigations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Creatinine renal clearance increased | Investigations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| White blood cell count increased | Investigations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Brain injury | Nervous system disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Generalised tonic-clonic seizure | Nervous system disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Metabolic encephalopathy | Nervous system disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Posterior reversible encephalopathy syndrome | Nervous system disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Tachypnoea | Respiratory, thoracic and mediastinal disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Penile swelling | Reproductive system and breast disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Scrotal swelling | Reproductive system and breast disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Rash generalised | Skin and subcutaneous tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Pain of skin | Skin and subcutaneous tissue disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Phlebitis | Vascular disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA V 20.1/23.1 | Non-systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Communication Center | Merck KGaA Darmstadt, Germany | +49-6151-72-5200 | service@emdgroup.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 12, 2018 | Feb 5, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000707607 | tepotinib |
| D000077157 | Sorafenib |
| ID | Term |
|---|---|
| D010671 | Phenylurea Compounds |
| D014508 | Urea |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009536 | Niacinamide |
| D009539 | Nicotinic Acids |
| D000147 | Acids, Heterocyclic |
| D006571 | Heterocyclic Compounds |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OG002 |
| 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. |
|
|
|
|
|
|
|
|
|
|
| Units | Counts |
|---|
| Participants |
|
|
|
|
|
Participants received Tepotinib 1000 mg orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal. |
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| 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. |
|
|
Participants received Tepotinib 1000 mg orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.
|
|
|
|
|
|
|
|
|
|
|
Participants randomized to receive Sorafenib 400 mg orally twice daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.
|
|
|
Participants randomized to receive Sorafenib 400 mg orally twice daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal. |
|
|
|
|
|
|
|
|
Participants randomized to receive Sorafenib 400 mg orally twice daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.
|
|