This study was to assess the antitumor activity, safety, tolerability, and pharmacokinetics (PK) of the Mesenchymal-epithelial Transition Factor (MET) inhibitor tepotinib combined with the 3rd generation EGFR inhibitor osimertinib in participants with advanced or metastatic non-small cell lung cancer (NSCLC).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
140
Participants were administered with Tepotinib orally once daily at a dose of 500 mg.
Participants received Osimertinib at a dose of 80 mg orally once daily.
Combined Therapy (Tepotinib+Osimertinib): Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version (NCI-CTCAE v 5.0)
DLTs are defined as any of the following toxicities and judged by the Investigator and/or the Sponsor to be not attributable to the disease or disease-related processes under investigation: Grade 4 neutropenia for more than 7 days; Grade greater than or equal to (\>=) 3 febrile neutropenia; Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with non-traumatic bleeding; Grade \>= 3 nausea/vomiting and/or diarrhea that has not improved within 72 hours despite adequate and optimal treatment; Any other Grade \>= 3 non-hematological AE, except alopecia or Grade 3 nauseas/vomiting and/or diarrhea that has improved within 72 hours with optimal treatment.
Time frame: Up to Day 21 of Cycle 1 (each Cycle is of 21 days)
Combined Therapy: Objective Response According to Response Evaluation Criteria in Solid Tumors(RECIST)Version1.1as Per Independent Review Committee in Participants With MET Amplification Determined Centrally by Fluorescence in Situ Hybridization(FISH)
Objective response was defined as percentage of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD) .CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Combined Therapy: Objective Response According to Response Evaluation Criteria in Solid Tumors(RECIST)Version1.1as Per Independent Review Committee in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing
Objective response was defined as percentage of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD) .CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
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Yuma Regional Medical Center
Yuma, Arizona, United States
Compassionate Care Research Group Inc - Edinger Medical Group, Inc.
Fountain Valley, California, United States
Memorial Care
Long Beach, California, United States
Ventura County Hematology Oncology Specialists
Oxnard, California, United States
Innovative Clinical Research Institute
Whittier, California, United States
Eastern Connecticut Hematology & Oncology Associates
Norwich, Connecticut, United States
Holy Cross
Fort Lauderdale, Florida, United States
Memorial Healthcare System
Hollywood, Florida, United States
Cancer Specialists of North Florida
Jacksonville, Florida, United States
Ocala Oncology
Ocala, Florida, United States
...and 169 more locations
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Monotherapy (Tepotinib): Objective Response According to Response Evaluation Criteria in Solid Tumors(RECIST)Version1.1 as Per Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH
Objective response was defined as percentage of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD) .CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs
An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not. 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. TEAEs were defined as events with onset date or worsening during the on-treatment period. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs is defined as reasonably related to the study intervention.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs
The laboratory measurements included hematology, biochemistry, coagulation and urinalysis. Number of participants with clinically significant abnormalities in laboratory values reported as treatment related TEAEs were reported. Clinical significance was decided by investigator.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Number of Participants With Markedly Abnormal Vital Sign Measurements
Vital signs included systolic blood pressure (SBP) and diastolic blood pressure (DBP), pulse rate (PR), respiratory rate (RR) body weight (BW) and body temperature (BT). Markedly abnormal value (MAV) criteria for vital signs: SBP and DBP: maximal on treatment (TR) increase or decrease greater than (\>) 40 millimeter of mercury (mmHg); PR: maximal on TR increase or decrease \>40 beats per minute (bpm); RR: maximal on TR increase or decrease \>10 breaths per minute (breaths/minute), BW: maximum on TR increase or decrease \>=10% and BT: maximal on TR increase greater than or equal to (\>=)2 degree Celsius. Number of participants who met the MAV criteria for vital signs at least once post dose were reported.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score
ECOG performance status measured to assess participant's performance status on a scale of 0 to 5, where 0 = Fully active, able to carry on all pre-disease activities without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities; 3 = Capable of only limited self-care, confined to bed/chair for more than 50 percent of waking hours; 4 = Completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5 = dead. ECOG performance status was reported in terms of number of participants with shifts in score from baseline value vs worst post-baseline value (that is \[i.e.\] highest score).
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings
Electrocardiograms (ECG) was obtained after the participant has been in a semi-supine position for at least 5 min. ECG parameters included heart rate, PQ/PR duration, QRS and QT duration, QT Interval. Clinical significance was determined by the investigator. Number of participants with clinically significant abnormalities in 12-lead ECG were reported.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Combined Therapy: Objective Response According to Response Evaluation Criteria in Solid Tumors(RECIST)Version1.1 Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH
Objective response was defined as percentage of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Combined Therapy (Tepotinib + Osimertinib): Number of Participants With Confirmed Complete Response (CR) Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH
Confirmed CR was defined as the disappearance of all evidence of target and non-target lesions.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Combined Therapy (Tepotinib + Osimertinib): Number of Participants With Confirmed Complete Response (CR) Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH
Confirmed CR was defined as the disappearance of all evidence of target and non-target lesions.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Combined Therapy (Tepotinib + Osimertinib): Duration of Response Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH
DOR was defined for participants with objective response, as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months
Combined Therapy (Tepotinib + Osimertinib): Duration of Response Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH
DOR was defined for participants with objective response, as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months
Combined Therapy (Tepotinib + Osimertinib): Disease Control Rate Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH
Disease control rate is defined as the percentage of participants with objective resposne (complete resposne \[CR\] or partial resposne \[PR\] or stable disease \[SD\]). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD while on study. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Combined Therapy (Tepotinib + Osimertinib): Disease Control Rate Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH
Disease control rate is defined as the percentage of participants with objective resposne (complete resposne \[CR\] or partial resposne \[PR\] or stable disease \[SD\]). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD while on study. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Combined Therapy (Tepotinib + Osimertinib): Progression-Free Survival (PFS) According to RECIST Version1.1 as Assessed by the Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH
PFS was defined as the time is defined as the time from first administration of study treatment to the date of the first documentation of PD or death due to any cause within 126 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: Time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, assessed approximately up to 42 months
Combined Therapy (Tepotinib + Osimertinib): Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors(RECIST)Version1.1as Assessed by the Investigator in Participants With MET Amplification Determined Centrally by FISH
PFS was defined as the time is defined as the time from first administration of study treatment to the date of the first documentation of PD or death due to any cause within 126 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, assessed approximately up to 42 months
Combined Therapy (Tepotinib + Osimertinib): Overall Survival in Participants With MET Amplification Determined Centrally by FISH
Overall survival is defined as the time from first administration of study treatment to the date of death.
Time frame: Time from first administration of study treatment to the date of death, assessed approximately up to 42 months
Combined Therapy: Objective Response According to Response Evaluation Criteria in Solid Tumors(RECIST)Version1.1as Assessed by Investigator in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing
Objective response was defined as percentage of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Combined Therapy (Tepotinib + Osimertinib): Number of Participants With Confirmed Complete Response (CR) Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing
Confirmed CR was defined as the disappearance of all evidence of target and non-target lesions.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Combined Therapy (Tepotinib + Osimertinib): Number of Participants With Confirmed Complete Response (CR) Assessed by Investigator in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing
Confirmed CR was defined as the disappearance of all evidence of target and non-target lesions.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Combined Therapy (Tepotinib + Osimertinib): Duration of Response Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing
DOR was defined for participants with objective response, as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months
Combined Therapy (Tepotinib + Osimertinib): Duration of Response Assessed by Investigator in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing
DOR was defined for participants with objective response, as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months
Combined Therapy (Tepotinib + Osimertinib): Disease Control Rate Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing
Disease control rate is defined as the percentage of participants with objective resposne (complete resposne \[CR\] or partial resposne \[PR\] or stable disease \[SD\]). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD while on study. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Combined Therapy (Tepotinib + Osimertinib): Disease Control Rate Assessed by Investigator in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing
Disease control rate is defined as the percentage of participants with objective resposne (complete resposne \[CR\] or partial resposne \[PR\] or stable disease \[SD\]). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD while on study. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Combined Therapy (Tepotinib + Osimertinib): Progression-Free Survival (PFS) According to RECIST Version1.1 as Per Independent Review Committee in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing
PFS was defined as the time is defined as the time from first administration of study treatment to the date of the first documentation of PD or death due to any cause within 126 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: Time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, assessed approximately up to 42 months
Combined Therapy ((Tepotinib + Osimertinib): Progression-Free Survival (PFS) According to RECIST Version1.1 as Assessed by the Investigator in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing
PFS was defined as the time is defined as the time from first administration of study treatment to the date of the first documentation of PD or death due to any cause within 126 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: Time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, assessed approximately up to 42 months
Combined Therapy (Tepotinib + Osimertinib): Overall Survival in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing
Overall survival is defined as the time from first administration of study treatment to the date of death.
Time frame: Time from first administration of study treatment to the date of death, assessed approximately up to 42 months
Monotherapy (Tepotinib): Objective Response According to Response Evaluation Criteria in Solid Tumors(RECIST)Version1.1as Per Investigator in Participants With MET Amplification Determined Centrally by Fluorescence in Situ Hybridization(FISH)
Objective response was defined as percentage of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD) .CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Monotherapy (Tepotinib): Number of Participants With Confirmed Complete Response (CR) Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH
Confirmed CR was defined as the disappearance of all evidence of target and non-target lesions.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Monotherapy (Tepotinib): Number of Participants With Confirmed Complete Response (CR) Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH
Confirmed CR was defined as the disappearance of all evidence of target and non-target lesions.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Monotherapy (Tepotinib): Duration of Response Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH
DOR was defined for participants with objective response, as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months
Monotherapy (Tepotinib): Duration of Response Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH
DOR was defined for participants with objective response, as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months
Monotherapy (Tepotinib): Disease Control Rate Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH
Disease control rate is defined as the percentage of participants with objective resposne (complete resposne \[CR\] or partial resposne \[PR\] or stable disease \[SD\]). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD while on study. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Monotherapy (Tepotinib): Disease Control Rate Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH
Disease control rate is defined as the percentage of participants with objective resposne (complete resposne \[CR\] or partial resposne \[PR\] or stable disease \[SD\]). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD while on study. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Monotherapy (Tepotinib): Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors(RECIST)Version1.1as Assessed by the Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH
PFS was defined as the time is defined as the time from first administration of study treatment to the date of the first documentation of PD or death due to any cause within 126 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: Time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, assessed approximately up to 42 months
Monotherapy (Tepotinib): Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors(RECIST)Version1.1as Assessed by the Investigator in Participants With MET Amplification Determined Centrally by FISH
PFS was defined as the time is defined as the time from first administration of study treatment to the date of the first documentation of PD or death due to any cause within 126 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: Time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, assessed approximately up to 42 months
Combined Therapy (Tepotinib + Osimertinib): Change From Baseline in European Quality Of Life 5-dimensions (EQ-5D-5L) Visual Analog Scale (VAS) at Safety Follow-up (42 Months)
The EQ-5D-5L questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L profile defines health in terms of mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. Each dimension has five levels: 1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, and 5: extreme problems. The responses were used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 was the worst health you can imagine and 100 was the best health you can imagine.
Time frame: Baseline, safety follow-up (assessed up to 42 months)
Combined Therapy (Tepotinib + Osimertinib): Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status) at Safety Follow-up (42 Months)
EORTC QLQ-C30 was a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). The EORTC QLQ-C30 GHS/QoL score ranged from 0 to 100; High score indicated better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL.
Time frame: Baseline, safety follow-up (up to 42 months)
Combined Therapy (Tepotinib + Osimertinib): Change From Baseline in Health-Related Quality of Life as Assessed by Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) at Safety Follow-up (42 Months)
NSCLC-SAQ was a question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 5 domains: cough, pain, dyspnea, fatigue, and appetite. The NSCLC-SAQ score ranged from 0 to 20; High score indicated more severe NSCLC-related symptomatology. mains: cough, pain, dyspnea, fatigue, and appetite.
Time frame: Baseline, safety follow-up (up to 42 months)
Combined Therapy (Tepotinib + Osimertinib): Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104
Area under the plasma concentration versus 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 calculated according to the mixed log-linear trapezoidal rule.
Time frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after tepotinib and Osimertinib administration at Day 1 of Cycle 1 and Day 15 of Cycle 1 (each Cycle is of 21 days) ]
Combined Therapy (Tepotinib + Osimertinib): Maximum Observed Plasma Concentration (Cmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104
Cmax was obtained directly from the concentration versus time curve.
Time frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after tepotinib and Osimertinib administration at Day 1 of Cycle 1 and Day 15 of Cycle 1 (each Cycle is of 21 days) ]
Combined Therapy (Tepotinib + Osimertinib): Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104
Tmax was obtained directly from the concentration versus time curve.
Time frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after tepotinib and Osimertinib administration at Day 1 of Cycle 1 and Day 15 of Cycle 1 (each Cycle is of 21 days) ]
Combined Therapy (Tepotinib + Osimertinib): Apparent Total Body Clearance (CL/f) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104
CL/f was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-t + Clast pred/Lambda Z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLQ) and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Time frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after tepotinib and Osimertinib administration at Day 1 of Cycle 1 and Day 15 of Cycle 1 (each Cycle is of 21 days) ]
Combined Therapy (Tepotinib + Osimertinib): Apparent Volume Of Distribution (Vz/F) of of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104
Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf\*Lambda Z), where AUC0-inf = (AUC0-t + Clast pred/Lambda Z). Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Time frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after tepotinib and Osimertinib administration at Day 1 of Cycle 1 and Day 15 of Cycle 1 (each Cycle is of 21 days) ]
Percentage of Participants With Resistant Mutations of the Epidermal Growth Factor Receptor (EGFR) Gene or Other Pathways as Assessed in Circulating Tumor Deoxyribonucleic Acid (ctDNA)
Percentage of participants with resistant mutations of the EGFR gene or other pathways as assessed in ctDNA were reported.
Time frame: From Day 1 of Cycle 3 up to end of treatment (14 days after last dose, approximately assessed up to 35.6 months) (each Cycle is for 21 days)