Patients With Solid Tumors, Either Refractory to Standard Therapy or for Which no Effective Standard Therapy is AvailablePhase 1NCT01014936
First-in-Man, Dose-escalation Trial of C-met Kinase Inhibitor MSC2156119J in Subjects With Advanced Solid Tumors
A Phase 1 study testing MSC2156119J in people with Patients With Solid Tumors, Either Refractory to Standard Therapy or for Which no Effective Standard Therapy is Available, run by EMD Serono at 1 site in United States.
Trial summary
This is a an open-label, dose-escalation, first-in-man (FIM) study designed to explore MSC2156119J, in subjects with advanced solid tumors who have not responded to previous therapies or for whom no other therapies are available. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Patients With Solid Tumors, Either Refractory to Standard Therapy or for Which no Effective Standard Therapy is Available
- What is being tested?
- MSC2156119J
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 149 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Nov 2009to 31 Oct 2015
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject should read and fully understand the requirements of the trial, be willing to comply with all trial visits and assessments, and be willing and able to give informed consent
- Histologically or cytologically confirmed solid tumor, either refractory to standard therapy or for which no effective standard therapy is available
- Measurable or evaluable disease, as defined by RECIST 1.0
- Estimated life expectancy greater than (>) three months
- Men or women aged greater than or equal to (>=) 18 years
- Women of childbearing potential must have a negative blood pregnancy test at the Screening Visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are post-menopausal for at least 12 months, are surgically sterile, or are sexually inactive.
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- Subjects and their partners must be willing to avoid pregnancy during the trial and until three months after the last trial treatment. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception as approved by the investigator, such as a two-barrier method or one-barrier method with spermicide or intrauterine device. This requirement begins two weeks before receiving the first trial treatment and ends one month after receiving the last treatment.
- ECOG performance status of 0 to 2
- Adequate hematological function:
- Hemoglobin >= 9.0 g/dL
- Neutrophils > 1.5 x 109/L
- Platelets >= 75 x 109/L
- Adequate liver function:
- Total bilirubin less than or equal to (<=) 1.5 x ULN (upper limit to normal)
- AST/ ALT ≤ 2.5 x ULN
- For subjects with liver metastases:
- Total bilirubin ≤ 1.5 x ULN
- AST/ ALT ≤ 5 x ULN
- Adequate renal function:
- Serum creatinine < 1.5 x ULN, and/or
- Calculated creatinine clearance > 60 mL/min
- Resolution of all acute chemotherapy, radiotherapy or surgery-related AEs to Grade <= 2, except for alopecia
- Recovery from any surgical intervention
- Subjects enrolling after the MTD has been determined must present specific c Met alterations (mutation, overexpression, amplification
Who cannot join
- Received chemotherapy, immunotherapy, hormonal therapy (except subjects with prostate cancer), biologic therapy, or any other investigational agent or anticancer therapy within 28 days (or five half-lives for non-cytotoxics, whichever is shorter), of Day 1 of trial treatment (six weeks for nitrosureas or mitomycin C)
- Received extensive prior radiotherapy on more than 30% of bone marrow
- Symptomatic primary tumors or metastasis of brain and/or central nervous system, uncontrolled with antiepileptics and requiring high doses of steroids
- Known HIV positivity, active hepatitis C, or active hepatitis B
- Medical history of liver fibrosis/ cirrhosis
- Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such
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- Medical history of difficulty swallowing, malabsorption or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the tested product
- Medical history of surgery within six weeks prior to enrollment
- Impaired cardiac function (left ventricular ejection fraction < 45% defined by echocardiograph, serious arrhythmia, unstable angina pectoris, congestive heart failure NYHA III and IV, myocardial infarction within the last 12 months prior to trial entry; signs of pericardial effusion)
- Hypertension uncontrolled by standard therapies (not stabilized to 150/90 mm Hg)
- Peripheral neuropathy Grade >= 2
- Medical history of any other significant medical disease, major surgery, or psychiatric condition that might impair the subject's well being or preclude full participation in the trial
- Women who are pregnant or nursing
- Known drug abuse or alcohol abuse
- Participation in another clinical trial within the past 28 days
- Requires concurrent treatment with a non-permitted drug
- Known hypersensitivity to any of the trial treatment ingredients
- Legal incapacity or limited legal capacity
- Any other reason that, in the opinion of the principal investigator, precludes the subject from participating in the trial
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Open-label, Non-randomized, Dose-escalation First-in-man Trial to Investigate the c-Met Kinase Inhibitor MSC2156119J Under Three Different Regimens in Subjects With Advanced Solid Tumors
This is a an open-label, dose-escalation, first-in-man (FIM) study designed to explore MSC2156119J, in subjects with advanced solid tumors who have not responded to previous therapies or for whom no other therapies are available.
Subjects will be assigned one of the dosing regimens:
- Regimen 1: MSC2156119J once daily for 14 days, followed by 7 days with no treatment (21-day cycle)
- Regimen 2: MSC2156119J three times per week (e.g., Days 1, 3, and 5) for three weeks (21-day cycle)
- Regimen 3: MSC2156119J every day for three weeks (21-day cycle)
- Being tested
- MSC2156119J
- Keywords
- Phase 1, advanced solid tumors, refractory to standard therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MSC2156119JDrug
Also called EMD 1214063, Tepotinib
| Study group | Role | What they receive |
|---|---|---|
| MSC2156119J Regimen 1 | Experimental | Subjects will be administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1. Receives: Drug: MSC2156119J |
| MSC2156119J Regimen 2 | Experimental | Subjects will be administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2. Receives: Drug: MSC2156119J |
| MSC2156119J Regimen 3 | Experimental | Subjects will be administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3. Receives: Drug: MSC2156119J |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Any Dose Limiting Toxicity (DLT)
DLT was defined as one of the following adverse events (AEs) observed during Cycle1, regardless of MSC2156119J relationship, excluding AEs assessed by investigator exclusively related to subject's underlying disease or medical condition: Grade 4 neutropenia for >7 days; Grade >=3 febrile neutropenia for >1 day; Grade 4 thrombocytopenia/Grade 3 with bleeding; Grade >=3 nausea and emesis, despite optimal treatment; Grade >=3 non-hematological AE, except emesis and nausea with no adequate therapy and alopecia, Grade >= 3 liver AE with a recovery period of >7 days or to Grade <=1 for subjects without liver metastases or to <=2 for subjects with liver metastases; Grade >=3 lipase and/or amylase rise with pancreatitis confirmation, either based on clinical or radiological signs. Any AE not otherwise defined as a DLT that, due to prolonged recovery to Grade <=1 or baseline status, leads to delay of above 21 days in planned administration of study drug.
Measured: Day 1, 3, 8, 14, 17 of Cycle 1 (for Regimen 1 and 3); Day 1, 3, 8, 15, 19 of Cycle 1 (for Regimen 2)
Recommended Phase 2 Dose (RP2D)
MTD was defined as the dose level at which 2 out of 3 subjects or 2 out of 6 subjects experienced a DLT. The primary endpoint was to determine MTD of MSC2156119J for each of the 3 treatment regimens in subjects with advanced solid tumors. However, during the course of the trial it was established that the MTD could not be determined and instead, RP2D was to be determined.
Measured: Cycle 1 (Day 1 to Day 21)
Number of Subjects With Treatment-Related Adverse Events
Related AE was defined as any untoward medical occurrence which was considered to have a relationship with the study drug (suspected to be reasonably related to the study drug or AE was medically (pharmacologically/clinically) attributed to the study drug as per Investigator's assessment.
Measured: Baseline up to 158.01 weeks
Secondary outcomes (55)
Number of Subjects With Treatment-Emergent AEs (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death
AE was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this the study drug. 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 up to 33 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. TEAEs include both Serious TEAEs and non-serious TEAEs.
Measured: Baseline up to 158.01 weeks
Observed Maximum Plasma Concentration (Cmax) After Single Dose of MSC2156119J: Regimen 1
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Observed Maximum Plasma Concentration (Cmax) After Single Dose of MSC2156119J: Regimen 2
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Observed Maximum Plasma Concentration (Cmax) After Single Dose of MSC2156119J: Regimen 3
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Observed Maximum Plasma Concentration (Cmax) After Multiple Dose of MSC2156119J: Regimen 1
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Observed Maximum Plasma Concentration (Cmax) After Multiple Dose of MSC2156119J: Regimen 2
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1
Observed Maximum Plasma Concentration (Cmax) After Multiple Dose of MSC2156119J: Regimen 3
Reporting group "MSC2156119J 1200 mg: Fasted" is not applicable for Multiple Dosing because only one subject was erroneously dosed with 1200 mg in fasted state as a single dose in Regimen 3. For multiple dose PK profile (Study Day 14), this subject was included in reporting group "MSC2156119J 1400 mg: Fed".
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Time To Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J: Regimen 1
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Time To Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J: Regimen 2
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24, 48, 49.32 hours post-dose on Day 1 Cycle 1
Time To Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J: Regimen 3
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Time To Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J: Regimen 1
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Time To Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J: Regimen 2
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1
Time To Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J: Regimen 3
Reporting group "MSC2156119J 1200 mg: Fasted" is not applicable for Multiple Dosing because only one subject was erroneously dosed with 1200 mg in fasted state as a single dose in Regimen 3. For multiple dose PK profile (Study Day 14), this subject was included in reporting group "MSC2156119J 1400 mg: Fed".
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Apparent Terminal Half-life ( t1/2) After Single Dose Of MSC2156119J: Regimen 1
Apparent Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Apparent Terminal Half-life ( t1/2) After Single Dose Of MSC2156119J: Regimen 2
Apparent Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Apparent Terminal Half-life ( t1/2) After Single Dose Of MSC2156119J: Regimen 3
Apparent Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Apparent Terminal Half-life (t1/2) After Multiple Dose Of MSC2156119J: Regimen 1
Apparent terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Apparent Terminal Half-life (t1/2) After Multiple Dose Of MSC2156119J: Regimen 2
Apparent terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1
Apparent Terminal Half-life (t1/2) After Multiple Dose Of MSC2156119J: Regimen 3
Apparent terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Area Under Plasma Concentration Versus Time Curve From Time Zero to Last Sampling Time (AUC0-t) After First Dose of MSC2156119J: Regimen 1
Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time (AUC0-t) After First Dose of MSC2156119J: Regimen 2
Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the LLQ. AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time (AUC0-t) After First Dose of MSC2156119J: Regimen 3
Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the LLQ. AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time (AUC0-t) After Multiple Dose of MSC2156119J : Regimen 1
Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the LLQ. AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time (AUC0-t) After Multiple Dose of MSC2156119J : Regimen 2
Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the LLQ. AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time (AUC0-t) After Multiple Dose of MSC2156119J : Regimen 3
Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the LLQ. AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. Reporting group "MSC2156119J 1200 mg: Fasted" is not applicable for Multiple Dosing because only one subject was erroneously dosed with 1200 mg in fasted state as a single dose in Regimen 3. For multiple dose PK profile (Study Day 14), this subject was included in reporting group "MSC2156119J 1400 mg: Fed".
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) After Single Dose Of MSC2156119J: Regimen 1
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the LLQ and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) After Single Dose Of MSC2156119J: Regimen 2
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the LLQ and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) After Single Dose Of MSC2156119J: Regimen 3
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the LLQ and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Single Dose of MSC2156119: Regimen 1
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Single Dose of MSC2156119: Regimen 2
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24, 48 hours post-dose on Day 1 Cycle 1
Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Single Dose of MSC2156119: Regimen 3
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Multiple Dose of MSC2156119: Regimen 1
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Multiple Dose of MSC2156119: Regimen 2
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24, 48 hours post-dose on Day 19 Cycle 1
Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Multiple Dose of MSC2156119: Regimen 3
Reporting group "MSC2156119J 1200 mg: Fasted" is not applicable for Multiple Dosing because only one subject was erroneously dosed with 1200 mg in fasted state as a single dose in Regimen 3. For multiple dose PK profile (Study Day 14), this subject was included in reporting group "MSC2156119J 1400 mg: Fed".
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Apparent Body Clearance (CL/f) After First Dose of MSC2156119J: Regimen 1
Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0-inf.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Apparent Body Clearance (CL/f) After First Dose of MSC2156119J: Regimen 2
Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0-inf.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Apparent Body Clearance (CL/f) After First Dose of MSC2156119J: Regimen 3
Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0-inf.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Apparent Volume of Distribution (Vz/f) After First Dose of MSC2156119J: Regimen 1
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 serum concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Apparent Volume of Distribution (Vz/f) After First Dose of MSC2156119J: Regimen 2
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 serum concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Apparent Volume of Distribution (Vz/f) After First Dose of MSC2156119J: Regimen 3
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 serum concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Apparent Volume of Distribution (Vz/f) After Multiple Dose of MSC2156119J: Regimen 1
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 serum concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Apparent Volume of Distribution (Vz/f) After Multiple Dose of MSC2156119J: Regimen 2
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 serum concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1
Apparent Volume of Distribution (Vz/f) After Multiple Dose of MSC2156119J: Regimen 3
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 serum concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Apparent Terminal Rate Constant (λz) After Single Dose of MSC2156119J: Regimen 1
Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Apparent Terminal Rate Constant (λz) After Single Dose of MSC2156119J: Regimen 2
Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Apparent Terminal Rate Constant (λz) After Single Dose of MSC2156119J: Regimen 3
Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Apparent Terminal Rate Constant (λz) After Multiple Dose of MSC2156119J: Regimen 1
Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Apparent Terminal Rate Constant (λz) After Multiple Dose of MSC2156119J: Regimen 2
Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1
Apparent Terminal Rate Constant (λz) After Multiple Dose of MSC2156119J: Regimen 3
Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Measured: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Absolute Change From Baseline in Cytoplasm and Membrane H-Score at Day 1 Cycle 2
Histo score (H-score) is a composite score that comprises of intensity and percentage of staining and is used for assessing the amount of protein or phospho-protein present in a biopsy sample. The composite score obtained by H-score is derived by summing the percentages of cell staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+; where 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). The composite H-score ranges from 0 to 300, with a score of 0 representing the absence of any of the target protein and an H-score of 300 representing maximum staining and intensity of the target protein.
Measured: Baseline, Day 1 Cycle 2
Fold Change From Baseline in Cytoplasm and Membrane H-Score at Day 1 Cycle 2
Histo score (H-score) is a composite score that comprises of intensity and percentage of staining and is used for assessing the amount of protein or phospho-protein present in a biopsy sample. The composite score obtained by H-score is derived by summing the percentages of cell staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+; where 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). The composite H-score ranges from 0 to 300, with a score of 0 representing the absence of any of the target protein and an H-score of 300 representing maximum staining and intensity of the target protein. Fold change = on-treatment value/ baseline value
Measured: Baseline, Day 1 Cycle 2
Number of Subjects With Monovalent Antagonist Antibody to Receptor MET (MetMAb) Score (MMS)
MetMAb score was used to assess the tumor c-Met expression and ranged from 0 to 3, where a score of 0 corresponds to the lowest c-Met expression and a score of 3 corresponds to the highest c-Met expression in tumor tissue by immunohistochemistry.
Measured: Day 1 Cycle 2
Relative Percentage Change In Sum of Longest Diameter (SOLD) of Target Lesions to Post-Baseline Nadir
The post-baseline nadir was defined as the the smallest SOLD recorded after baseline. The relative change (%) was derived based on the SOLD of target lesions as follows: 100* (SOLD at post-baseline nadir - baseline SOLD) / baseline SOLD.
Measured: Baseline, On Treatment (up to 153.3 weeks)
Number of Subjects With Best Overall Response (BOR)
Number of subjects with BOR in each category (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) was reported. CR: defined as disappearance of all target and all non-target lesions. 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 sum of longest diameter of target lesions, taking as reference the baseline sum of longest diameter. PD:defined as at least a 20% increase in sum of longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or unequivocal progression of existing non-target lesions. SD: defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of longest diameter while on study.
Measured: Baseline up to 153.3 weeks
Progression-free Survival (PFS)
PFS was defined as the time (in months) between the first dosing day and radiographic PD or clinical PD (as recorded on the study termination form) or death, if death occurred within 12 weeks (84 days) after the last tumor assessment without documented progressive disease, whichever occurred first. Any subject with neither assessment of tumor progression, nor death within 12 weeks after last tumor assessment date was censored on the date of last tumor assessment.
Measured: Baseline up to 153.3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2009 (estimated)
- Study start30 Nov 2009
- Primary completion31 Oct 2015
- Study completion31 Oct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Patients With Solid Tumors, Either Refractory to Standard Therapy or for Which no Effective Standard Therapy is AvailableStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 149 participants (actual)
Sponsor and investigators
- Lead sponsor
- EMD Serono
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, EMD Serono, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01014936
- Sponsor's protocol ID
- EMR200095_001
- Other IDs
- 2013-003767-63
- Status last verified
- Aug 2022
- First submitted
- 13 Nov 2009
- Last updated
- 24 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Falchook GS, Kurzrock R, Amin HM, Xiong W, Fu S, Piha-Paul SA, Janku F, Eskandari G, Catenacci DV, Klevesath M, Bruns R, Stammberger U, Johne A, Bladt F, Friese-Hamim M, Girard P, El Bawab S, Hong DS. First-in-Man Phase I Trial of the Selective MET Inhibitor Tepotinib in Patients with Advanced Solid Tumors. Clin Cancer Res. 2020 Mar 15;26(6):1237-1246. doi: 10.1158/1078-0432.CCR-19-2860. Epub 2019 Dec 10.
PubMed 31822497Xiong 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.
PubMed 35771259
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Open-label, Non-randomized, Dose-escalation First-in-man Trial to Investigate the c-Met Kinase Inhibitor MSC2156119J Under Three Different Regimens in Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01014936
- Acronym / sponsor ID
- EMR200095_001
- Keywords
- Phase 1, advanced solid tumors, refractory to standard therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 149 participants (actual)
- Lead sponsor
- EMD SeronoIndustry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Study start
- 30 Nov 2009 (actual)
- Primary completion
- 31 Oct 2015 (actual)
- Study completion
- 31 Oct 2015 (actual)
- First posted
- 17 Nov 2009 (estimated)
- Results
- Posted 17 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a an open-label, dose-escalation, first-in-man (FIM) study designed to explore MSC2156119J, in subjects with advanced solid tumors who have not responded to previous therapies or for whom no other therapies are available.
Subjects will be assigned one of the dosing regimens:
- Regimen 1: MSC2156119J once daily for 14 days, followed by 7 days with no treatment (21-day cycle)
- Regimen 2: MSC2156119J three times per week (e.g., Days 1, 3, and 5) for three weeks (21-day cycle)
- Regimen 3: MSC2156119J every day for three weeks (21-day cycle)
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MSC2156119J Regimen 1 | Experimental | Drug: MSC2156119JSubjects will be administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1. |
| MSC2156119J Regimen 2 | Experimental | Drug: MSC2156119JSubjects will be administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2. |
| MSC2156119J Regimen 3 | Experimental | Drug: MSC2156119JSubjects will be administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Subject should read and fully understand the requirements of the trial, be willing to comply with all trial visits and assessments, and be willing and able to give informed consent
- Histologically or cytologically confirmed solid tumor, either refractory to standard therapy or for which no effective standard therapy is available
- Measurable or evaluable disease, as defined by RECIST 1.0
- Estimated life expectancy greater than (>) three months
- Men or women aged greater than or equal to (>=) 18 years
Key exclusion criteria (19 listed)
- Received chemotherapy, immunotherapy, hormonal therapy (except subjects with prostate cancer), biologic therapy, or any other investigational agent or anticancer therapy within 28 days (or five half-lives for non-cytotoxics, whichever is shorter), of Day 1 of trial treatment (six weeks for nitrosureas or mitomycin C)
- Received extensive prior radiotherapy on more than 30% of bone marrow
- Symptomatic primary tumors or metastasis of brain and/or central nervous system, uncontrolled with antiepileptics and requiring high doses of steroids
- Known HIV positivity, active hepatitis C, or active hepatitis B
- Medical history of liver fibrosis/ cirrhosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MSC2156119JAlso: EMD 1214063, Tepotinib | Drug | MSC2156119J Regimen 1, MSC2156119J Regimen 2, MSC2156119J Regimen 3 |
Primary outcome
Number of Subjects With Any Dose Limiting Toxicity (DLT)
Time frame: Day 1, 3, 8, 14, 17 of Cycle 1 (for Regimen 1 and 3); Day 1, 3, 8, 15, 19 of Cycle 1 (for Regimen 2)
DLT was defined as one of the following adverse events (AEs) observed during Cycle1, regardless of MSC2156119J relationship, excluding AEs assessed by investigator exclusively related to subject's underlying disease or medical condition: Grade 4 neutropenia for >7 days; Grade >=3 febrile neutropenia for >1 day; Grade 4 thrombocytopenia/Grade 3 with bleeding; Grade >=3 nausea and emesis, despite optimal treatment; Grade >=3 non-hematological AE, except emesis and nausea with no adequate therapy and alopecia, Grade >= 3 liver AE with a recovery period of >7 days or to Grade <=1 for subjects without liver metastases or to <=2 for subjects with liver metastases; Grade >=3 lipase and/or amylase rise with pancreatitis confirmation, either based on clinical or radiological signs. Any AE not otherwise defined as a DLT that, due to prolonged recovery to Grade <=1 or baseline status, leads to delay of above 21 days in planned administration of study drug.
Recommended Phase 2 Dose (RP2D)
Time frame: Cycle 1 (Day 1 to Day 21)
MTD was defined as the dose level at which 2 out of 3 subjects or 2 out of 6 subjects experienced a DLT. The primary endpoint was to determine MTD of MSC2156119J for each of the 3 treatment regimens in subjects with advanced solid tumors. However, during the course of the trial it was established that the MTD could not be determined and instead, RP2D was to be determined.
Number of Subjects With Treatment-Related Adverse Events
Time frame: Baseline up to 158.01 weeks
Related AE was defined as any untoward medical occurrence which was considered to have a relationship with the study drug (suspected to be reasonably related to the study drug or AE was medically (pharmacologically/clinically) attributed to the study drug as per Investigator's assessment.
55 secondary outcomes
Number of Subjects With Treatment-Emergent AEs (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death
Time frame: Baseline up to 158.01 weeks
Observed Maximum Plasma Concentration (Cmax) After Single Dose of MSC2156119J: Regimen 1
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Observed Maximum Plasma Concentration (Cmax) After Single Dose of MSC2156119J: Regimen 2
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Observed Maximum Plasma Concentration (Cmax) After Single Dose of MSC2156119J: Regimen 3
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Observed Maximum Plasma Concentration (Cmax) After Multiple Dose of MSC2156119J: Regimen 1
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Observed Maximum Plasma Concentration (Cmax) After Multiple Dose of MSC2156119J: Regimen 2
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1
Observed Maximum Plasma Concentration (Cmax) After Multiple Dose of MSC2156119J: Regimen 3
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Time To Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J: Regimen 1
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Time To Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J: Regimen 2
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24, 48, 49.32 hours post-dose on Day 1 Cycle 1
Time To Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J: Regimen 3
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Time To Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J: Regimen 1
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Time To Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J: Regimen 2
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1
Time To Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J: Regimen 3
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Apparent Terminal Half-life ( t1/2) After Single Dose Of MSC2156119J: Regimen 1
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Apparent Terminal Half-life ( t1/2) After Single Dose Of MSC2156119J: Regimen 2
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Apparent Terminal Half-life ( t1/2) After Single Dose Of MSC2156119J: Regimen 3
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Apparent Terminal Half-life (t1/2) After Multiple Dose Of MSC2156119J: Regimen 1
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Apparent Terminal Half-life (t1/2) After Multiple Dose Of MSC2156119J: Regimen 2
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1
Apparent Terminal Half-life (t1/2) After Multiple Dose Of MSC2156119J: Regimen 3
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Area Under Plasma Concentration Versus Time Curve From Time Zero to Last Sampling Time (AUC0-t) After First Dose of MSC2156119J: Regimen 1
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time (AUC0-t) After First Dose of MSC2156119J: Regimen 2
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time (AUC0-t) After First Dose of MSC2156119J: Regimen 3
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time (AUC0-t) After Multiple Dose of MSC2156119J : Regimen 1
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time (AUC0-t) After Multiple Dose of MSC2156119J : Regimen 2
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time (AUC0-t) After Multiple Dose of MSC2156119J : Regimen 3
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) After Single Dose Of MSC2156119J: Regimen 1
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) After Single Dose Of MSC2156119J: Regimen 2
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) After Single Dose Of MSC2156119J: Regimen 3
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Single Dose of MSC2156119: Regimen 1
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Single Dose of MSC2156119: Regimen 2
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24, 48 hours post-dose on Day 1 Cycle 1
Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Single Dose of MSC2156119: Regimen 3
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Multiple Dose of MSC2156119: Regimen 1
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Multiple Dose of MSC2156119: Regimen 2
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24, 48 hours post-dose on Day 19 Cycle 1
Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Multiple Dose of MSC2156119: Regimen 3
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Apparent Body Clearance (CL/f) After First Dose of MSC2156119J: Regimen 1
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Apparent Body Clearance (CL/f) After First Dose of MSC2156119J: Regimen 2
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Apparent Body Clearance (CL/f) After First Dose of MSC2156119J: Regimen 3
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Apparent Volume of Distribution (Vz/f) After First Dose of MSC2156119J: Regimen 1
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Apparent Volume of Distribution (Vz/f) After First Dose of MSC2156119J: Regimen 2
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Apparent Volume of Distribution (Vz/f) After First Dose of MSC2156119J: Regimen 3
Time frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 31822497Falchook GS, Kurzrock R, Amin HM, Xiong W, Fu S, Piha-Paul SA, Janku F, Eskandari G, Catenacci DV, Klevesath M, Bruns R, Stammberger U, Johne A, Bladt F, Friese-Hamim M, Girard P, El Bawab S, Hong DS. First-in-Man Phase I Trial of the Selective MET Inhibitor Tepotinib in Patients with Advanced Solid Tumors. Clin Cancer Res. 2020 Mar 15;26(6):1237-1246. doi: 10.1158/1078-0432.CCR-19-2860. Epub 2019 Dec 10.
- Derived from this study: PubMed 35771259Xiong 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.
- Trial Awareness and Transparency websiteLink provided by the sponsor.
- US Medical Information website, Medical ResourcesLink provided by the sponsor.
- 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)Link provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
EMD Serono, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MSC2156119J in people with Patients With Solid Tumors, Either Refractory to Standard Therapy or for Which no Effective Standard Therapy is Available, run by EMD Serono at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects With Any Dose Limiting Toxicity (DLT) (time frame: Day 1, 3, 8, 14, 17 of Cycle 1 (for Regimen 1 and 3); Day 1, 3, 8, 15, 19 of Cycle 1 (for Regimen 2)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01014936, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2022.