Non-small Cell Lung Cancer
Conditions
Keywords
Tepotinib, Osimertinib, Non-Small Cell Lung Cancer, INSIGHT 2, MET amplified
Brief summary
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).
Interventions
DRUGTepotinib
Participants were administered with Tepotinib orally once daily at a dose of 500 mg.
DRUGOsimertinib
Participants received Osimertinib at a dose of 80 mg orally once daily.
Sponsors
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) histology (confirmed by either histology or cytology) with documented activating Epidermal Growth Factor Receptor (EGFR) mutation * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a minimum life expectancy of 12 weeks * Acquired resistance on previous first-line osimertinib. Participants must meet both of the following 2 criteria: * Radiological documentation of disease progression on first-line osimertinib * Objective clinical benefit documented during previous osimertinib therapy, defined by either partial or complete radiological response, or durable stable disease (SD) (SD should last greater than (\>) 6 months after initiation of osimertinib * Have received only first-line osimertinib as a prior line of therapy in the non curative advanced or metastatic NSCLC setting * MET amplification as determined by either FISH testing (central or local) on tumor tissue (TBx) or central blood-based next generation sequencing (LBx). Tumor and blood samples must be collected following progression on prior first-line osimertinib at Prescreening * Submission of tumor tissue and blood sample obtained after progression on first-line osimertinib, is mandatory for all patients for MET amplification testing * Submission of tumor tissue during Prescreening or Screening is mandatory for patients with tumor tissue tested by local FISH, to confirm MET amplification status. Central confirmation is not mandated prior to the start of study treatment * Other protocol defined inclusion criteria could apply
Exclusion criteria
* Spinal cord compression or brain metastasis unless asymptomatic, stable or not requiring steroids for at least 2 weeks prior to start of study intervention * Any unresolved toxicity Grade 2 or more according to National cancer institute common terminology criteria for adverse events( NCI-CTCAE) version 5, from previous anticancer therapy with the exception of alopecia * Inadequate hematological, liver and renal function * Impaired cardiac function * History of interstitial lung disease(ILD) or interstitial pneumonitis including radiation pneumonitis that required steroid treatment * Hypertension uncontrolled by standard therapies (not stabilized to \< 150/90 millimeter of mercury (mmHg) * Contraindication to the administration of osimertinib * Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Up to Day 21 of Cycle 1 (each Cycle is of 21 days) | 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. |
| 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) | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | 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. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | 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. |
| Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | 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. |
| Number of Participants With Markedly Abnormal Vital Sign Measurements | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | 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. |
| Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | 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). |
| Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | 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. |
| 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 | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | 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. |
| 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 | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | Confirmed CR was defined as the disappearance of all evidence of target and non-target lesions. |
| Combined Therapy (Tepotinib + Osimertinib): Number of Participants With Confirmed Complete Response (CR) Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | Confirmed CR was defined as the disappearance of all evidence of target and non-target lesions. |
| Combined Therapy (Tepotinib + Osimertinib): Duration of Response Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH | From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months | 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. |
| Combined Therapy (Tepotinib + Osimertinib): Duration of Response Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH | From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months | 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. |
| Combined Therapy (Tepotinib + Osimertinib): Disease Control Rate Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | 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. |
| Combined Therapy (Tepotinib + Osimertinib): Disease Control Rate Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | 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. |
| 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 | 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 | 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. |
| 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 | 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 | 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. |
| Combined Therapy (Tepotinib + Osimertinib): Overall Survival in Participants With MET Amplification Determined Centrally by FISH | Time from first administration of study treatment to the date of death, assessed approximately up to 42 months | Overall survival is defined as the time from first administration of study treatment to the date of death. |
| 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 | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | 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. |
| 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 | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | Confirmed CR was defined as the disappearance of all evidence of target and non-target lesions. |
| 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 | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | Confirmed CR was defined as the disappearance of all evidence of target and non-target lesions. |
| 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 | From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months | 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. |
| Combined Therapy (Tepotinib + Osimertinib): Duration of Response Assessed by Investigator in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing | From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months | 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. |
| 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 | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | 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. |
| Combined Therapy (Tepotinib + Osimertinib): Disease Control Rate Assessed by Investigator in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | 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. |
| 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 | 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 | 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. |
| 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 | 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 | 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. |
| 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) | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | 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. |
| Monotherapy (Tepotinib): Number of Participants With Confirmed Complete Response (CR) Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | Confirmed CR was defined as the disappearance of all evidence of target and non-target lesions. |
| Monotherapy (Tepotinib): Number of Participants With Confirmed Complete Response (CR) Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | Confirmed CR was defined as the disappearance of all evidence of target and non-target lesions. |
| Monotherapy (Tepotinib): Duration of Response Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH | From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months | 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. |
| Monotherapy (Tepotinib): Duration of Response Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH | From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months | 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. |
| Monotherapy (Tepotinib): Disease Control Rate Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | 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. |
| Monotherapy (Tepotinib): Disease Control Rate Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | 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. |
| 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 | 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 | 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. |
| 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 | 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 | 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. |
| 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) | Baseline, safety follow-up (assessed up to 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. |
| 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) | Baseline, safety follow-up (up to 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. |
| 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) | Baseline, safety follow-up (up to 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. |
| 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 | 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) ] | 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. |
| Combined Therapy (Tepotinib + Osimertinib): Maximum Observed Plasma Concentration (Cmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | 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) ] | Cmax was obtained directly from the concentration versus time curve. |
| Combined Therapy (Tepotinib + Osimertinib): Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | 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) ] | Tmax was obtained directly from the concentration versus time curve. |
| Combined Therapy (Tepotinib + Osimertinib): Apparent Total Body Clearance (CL/f) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | 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) ] | 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. |
| Combined Therapy (Tepotinib + Osimertinib): Apparent Volume Of Distribution (Vz/F) of of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | 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) ] | 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. |
| Combined Therapy (Tepotinib + Osimertinib): Overall Survival in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing | Time from first administration of study treatment to the date of death, assessed approximately up to 42 months | Overall survival is defined as the time from first administration of study treatment to the date of death. |
| 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) | 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) | Percentage of participants with resistant mutations of the EGFR gene or other pathways as assessed in ctDNA were reported. |
| 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 | Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) | 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. |
Countries
Belgium, China, France, Germany, Hong Kong, Italy, Japan, Malaysia, Netherlands, Russia, Singapore, South Korea, Spain, Taiwan, Thailand, United States, Vietnam
Contacts
STUDY_DIRECTORMedical Responsible
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tepotinib and Osimertinib Participants received a single oral dose of Tepotinib 500 milligrams (mg) followed by Omisertinib 80 mg once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal. | 128 |
| Tepotinib Mono-therapy Participants received a single oral dose of Tepotinib 500 mg until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal. | 12 |
| Total | 140 |
Baseline characteristics
| Characteristic | Tepotinib and Osimertinib | Tepotinib Mono-therapy | Total |
|---|---|---|---|
| Age, Continuous | 59 Years STANDARD_DEVIATION 10.8 | 61 Years STANDARD_DEVIATION 9.7 | 60 Years STANDARD_DEVIATION 10.7 |
| Race/Ethnicity, Customized Ethnicity-Hispanic or Latino | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Ethnicity-Not Hispanic or Latino | 124 Participants | 12 Participants | 136 Participants |
| Race/Ethnicity, Customized Ethnicity-Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race-Asian | 79 Participants | 6 Participants | 85 Participants |
| Race/Ethnicity, Customized Race-Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race-Not Collected At This Site | 4 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Race-Other | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race-White | 43 Participants | 4 Participants | 47 Participants |
| Sex: Female, Male Female | 74 Participants | 9 Participants | 83 Participants |
| Sex: Female, Male Male | 54 Participants | 3 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 59 / 128 | 7 / 12 |
| other Total, other adverse events | 123 / 128 | 12 / 12 |
| serious Total, serious adverse events | 49 / 128 | 2 / 12 |
Outcome results
Primary
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)
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic Epidermal Growth Factor Receptor mutation positive (EGFRm+) Non-Small Cell Lung Cancer (NSCLC) and Mesenchymal-Epithelial Transition factor (MET) amplification, determined centrally by FISH (central TBx FISH testing \[T+\]).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tepotinib + Osimertinib | 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) | 50.0 percentage of participants |
Primary
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)
Population: Safety run-in analysis set (SRIAS): all FAS/SAF participants treated during the safety run-in period who received at least 75% of the tepotinib and osimertinib planned dose and completed the DLT period (3 weeks after start of study treatment), or who experienced a DLT during the DLT period regardless of the received amount of each study treatment component.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tepotinib + Osimertinib | 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) | 1 Participants |
Secondary
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)
Population: The secondary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by liquid biopsy (LBx) test (L+).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tepotinib + Osimertinib | 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 | 48.4 percentage of participants |
Secondary
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.
Time frame: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Population: The secondary analysis set for efficacy included all modified Full Analysis Set (mFAS) participants with advanced or metastatic Epidermal Growth Factor Receptor mutation positive (EGFRm+) Non-Small Cell Lung Cancer (NSCLC) and Mesenchymal-Epithelial Transition factor (MET) amplification, determined centrally by liquid biopsy (LBx) test (L+).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tepotinib + Osimertinib | 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 | 54.8 percentage of participants |
Secondary
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)
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tepotinib + Osimertinib | 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 | 44.9 percentage of participants |
Secondary
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) ]
Population: As per changes in planned analysis, the PK parameter (CL/f) was not assessed.
Secondary
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) ]
Population: As per changes in planned analysis, the PK parameter (Vz/f) was not assessed.
Secondary
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) ]
Population: Pharmacokinetic analysis set included all FAS/SAF participants who have no important events affecting PK and provide at least one measurable post-dose concentration. 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 specified timepoints for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tepotinib + Osimertinib | 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 | Tepotinib: Cycle 1 Day 1 | 11600 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 40.8 |
| Tepotinib + Osimertinib | 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 | Tepotinib: Cycle 1 Day 15 | 26900 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 47.1 |
| Tepotinib + Osimertinib | 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 | MSC2571109A: Cycle 1 Day 1 | 2240 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 40 |
| Tepotinib + Osimertinib | 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 | MSC2571109A: Cycle 1 Day 15 | 5160 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 50.3 |
| Tepotinib + Osimertinib | 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 | MSC2571107A: Cycle 1 Day 1 | 497 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 292.6 |
| Tepotinib + Osimertinib | 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 | MSC2571107A: Cycle 1 Day 15 | 1180 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 624.7 |
| Tepotinib + Osimertinib | 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 | Osimertinib: Cycle 1 Day 1 | 9090 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 168.9 |
| Tepotinib + Osimertinib | 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 | Osimertinib: Cycle 1 Day 15 | 8710 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 41.3 |
| Tepotinib + Osimertinib | 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 | AZD5104: Cycle 1 Day 1 | 808 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 424.6 |
| Tepotinib + Osimertinib | 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 | AZD5104: Cycle 1 Day 15 | 1010 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 54.6 |
Secondary
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)
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tepotinib + Osimertinib | 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) | -6.5 score on a scale | Standard Deviation 25.17 |
Secondary
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)
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tepotinib + Osimertinib | 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) | -11 score on a scale | Standard Deviation 21.7 |
Secondary
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)
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tepotinib + Osimertinib | 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) | 2.0 score on a scale | Standard Deviation 4.26 |
Secondary
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)
Population: The secondary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by liquid biopsy (LBx) test (L+).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tepotinib + Osimertinib | 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 | 64.5 percentage of participants |
Secondary
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)
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Disease Control Rate Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH | 63.3 percentage of participants |
Secondary
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)
Population: The secondary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by liquid biopsy (LBx) test (L+).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Disease Control Rate Assessed by Investigator in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing | 67.7 percentage of participants |
Secondary
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)
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Disease Control Rate Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH | 64.3 percentage of participants |
Secondary
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
Population: The secondary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by liquid biopsy (LBx) test (L+). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tepotinib + Osimertinib | 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 | 5.7 months |
Secondary
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
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Duration of Response Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH | 8.5 months |
Secondary
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
Population: The secondary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by liquid biopsy (LBx) test (L+). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Duration of Response Assessed by Investigator in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing | 5.6 months |
Secondary
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
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Duration of Response Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH | 9.6 months |
Secondary
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) ]
Population: PK analysis set included all FAS/SAF participants who have no important events affecting PK and provide at least one measurable post-dose concentration. 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 specified timepoints for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Maximum Observed Plasma Concentration (Cmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | Tepotinib: Cycle 1 Day 1 | 660 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 38.7 |
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Maximum Observed Plasma Concentration (Cmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | Tepotinib: Cycle 1 Day 15 | 1220 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 45.1 |
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Maximum Observed Plasma Concentration (Cmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | MSC2571109A: Cycle 1 Day 1 | 167 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 41.1 |
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Maximum Observed Plasma Concentration (Cmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | MSC2571109A: Cycle 1 Day 15 | 274 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 45 |
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Maximum Observed Plasma Concentration (Cmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | MSC2571107A: Cycle 1 Day 1 | 38.4 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 26.57 |
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Maximum Observed Plasma Concentration (Cmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | MSC2571107A: Cycle 1 Day 15 | 57.0 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 27.19 |
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Maximum Observed Plasma Concentration (Cmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | Osimertinib: Cycle 1 Day 1 | 540 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 144.6 |
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Maximum Observed Plasma Concentration (Cmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | Osimertinib: Cycle 1 Day 15 | 468 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 51.2 |
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Maximum Observed Plasma Concentration (Cmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | AZD5104: Cycle 1 Day 1 | 43.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 421.2 |
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Maximum Observed Plasma Concentration (Cmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | AZD5104: Cycle 1 Day 15 | 50.9 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 63.8 |
Secondary
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)
Population: The secondary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by liquid biopsy (LBx) test (L+).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tepotinib + Osimertinib | 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 | 0 Participants |
Secondary
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)
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tepotinib + Osimertinib | 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 | 0 Participants |
Secondary
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)
Population: The secondary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by liquid biopsy (LBx) test (L+).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tepotinib + Osimertinib | 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 | 0 Participants |
Secondary
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)
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Number of Participants With Confirmed Complete Response (CR) Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH | 1 Participants |
Secondary
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
Population: The secondary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by liquid biopsy (LBx) test (L+).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Overall Survival in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing | 13.7 months |
Secondary
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
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Overall Survival in Participants With MET Amplification Determined Centrally by FISH | 17.8 months |
Secondary
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
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tepotinib + Osimertinib | 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 | 5.6 months |
Secondary
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
Population: The secondary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by liquid biopsy (LBx) test (L+).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tepotinib + Osimertinib | 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 | 5.6 months |
Secondary
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
Population: The secondary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by liquid biopsy (LBx) test (L+).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tepotinib + Osimertinib | 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 | 5.5 months |
Secondary
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
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tepotinib + Osimertinib | 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 | 5.9 months |
Secondary
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) ]
Population: PK analysis set included all FAS/SAF participants who have no important events affecting PK and provide at least one measurable post-dose concentration. 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 specified timepoints for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | Tepotinib: Cycle 1 Day 1 | 23.97 hours |
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | Tepotinib: Cycle 1 Day 15 | 5.13 hours |
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | MSC2571109A: Cycle 1 Day 1 | 24.00 hours |
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | MSC2571109A: Cycle 1 Day 15 | 0.25 hours |
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | MSC2571107A: Cycle 1 Day 1 | 24.00 hours |
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | MSC2571107A: Cycle 1 Day 15 | 24.00 hours |
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | Osimertinib: Cycle 1 Day 1 | 6.00 hours |
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | Osimertinib: Cycle 1 Day 15 | 5.00 hours |
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | AZD5104: Cycle 1 Day 1 | 8.00 hours |
| Tepotinib + Osimertinib | Combined Therapy (Tepotinib + Osimertinib): Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 | AZD5104: Cycle 1 Day 15 | 4.00 hours |
Secondary
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)
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tepotinib + Osimertinib | Monotherapy (Tepotinib): Disease Control Rate Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH | 25.0 percentage of participants |
Secondary
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)
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tepotinib + Osimertinib | Monotherapy (Tepotinib): Disease Control Rate Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH | 25.0 percentage of participants |
Secondary
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
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tepotinib + Osimertinib | Monotherapy (Tepotinib): Duration of Response Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH | 2.8 months |
Secondary
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
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tepotinib + Osimertinib | Monotherapy (Tepotinib): Duration of Response Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH | 2.8 months |
Secondary
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)
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tepotinib + Osimertinib | Monotherapy (Tepotinib): Number of Participants With Confirmed Complete Response (CR) Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH | 0 Participants |
Secondary
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)
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tepotinib + Osimertinib | Monotherapy (Tepotinib): Number of Participants With Confirmed Complete Response (CR) Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH | 0 Participants |
Secondary
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)
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tepotinib + Osimertinib | 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 | 8.3 percentage of participants |
Secondary
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)
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tepotinib + Osimertinib | 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) | 8.3 percentage of participants |
Secondary
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
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tepotinib + Osimertinib | 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 | 2.7 months |
Secondary
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
Population: The primary analysis set for efficacy included all mFAS participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH (central TBx FISH testing \[T+\]).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tepotinib + Osimertinib | 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 | 2.6 months |
Secondary
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)
Population: Safety (SAF) analysis set included all participants who were administered any dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tepotinib + Osimertinib | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings | 21 Participants |
| Tepotinib Monotherapy | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings | 1 Participants |
Secondary
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)
Population: Safety (SAF) analysis set included all participants who were administered any dose of any study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tepotinib + Osimertinib | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Anemia | 2 Participants |
| Tepotinib + Osimertinib | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Febrile neutropenia | 1 Participants |
| Tepotinib + Osimertinib | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Leukopenia | 1 Participants |
| Tepotinib + Osimertinib | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Myelosuppression | 1 Participants |
| Tepotinib + Osimertinib | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Neutropenia | 1 Participants |
| Tepotinib + Osimertinib | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Lymphocyte count decreased | 1 Participants |
| Tepotinib + Osimertinib | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Neutrophil count decreased | 2 Participants |
| Tepotinib + Osimertinib | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Platelet count decreased | 3 Participants |
| Tepotinib + Osimertinib | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | White blood cell count decreased | 3 Participants |
| Tepotinib + Osimertinib | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Alanine aminotransferase increased | 2 Participants |
| Tepotinib + Osimertinib | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Alkaline phosphatase increased | 1 Participants |
| Tepotinib + Osimertinib | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Lipase increased | 3 Participants |
| Tepotinib + Osimertinib | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Hypoalbuminemia | 1 Participants |
| Tepotinib + Osimertinib | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Urinary tract infection | 0 Participants |
| Tepotinib + Osimertinib | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Activated partial thromboplastin time | 0 Participants |
| Tepotinib + Osimertinib | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Prothrombin international normalized ratio | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Prothrombin international normalized ratio | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Anemia | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | White blood cell count decreased | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Febrile neutropenia | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Hypoalbuminemia | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Leukopenia | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Alanine aminotransferase increased | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Myelosuppression | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Activated partial thromboplastin time | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Neutropenia | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Alkaline phosphatase increased | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Lymphocyte count decreased | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Urinary tract infection | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Neutrophil count decreased | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Lipase increased | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs | Platelet count decreased | 0 Participants |
Secondary
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)
Population: Safety (SAF) analysis set included all participants who were administered any dose of any study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 0, worst post-baseline score 0 | 33 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 0, worst post-baseline score 4 | 0 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 0, worst post-baseline score 1 | 2 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 1, worst post-baseline score 1 | 59 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 0, worst post-baseline score 2 | 0 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 0, worst post-baseline score 1 | 16 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 0, worst post-baseline score 3 | 0 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 1, worst post-baseline score 2 | 21 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 0, worst post-baseline score 4 | 0 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 0, worst post-baseline score 5 | 0 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 0, worst post-baseline score 5 | 0 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 1, worst post-baseline score 3 | 6 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 0, worst post-baseline score missing | 0 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 0, worst post-baseline score 3 | 2 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 1, worst post-baseline score 0 | 19 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 1, worst post-baseline score 4 | 1 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 1, worst post-baseline score 1 | 71 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 0, worst post-baseline score missing | 0 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 1, worst post-baseline score 2 | 1 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 1, worst post-baseline score 5 | 1 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 1, worst post-baseline score 3 | 0 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 0, worst post-baseline score 2 | 3 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 1, worst post-baseline score 4 | 0 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 1, worst post-baseline score missing | 2 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 1, worst post-baseline score 5 | 0 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 1, worst post-baseline score 0 | 3 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 1, worst post-baseline score missing | 2 Participants |
| Tepotinib + Osimertinib | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 0, worst post-baseline score 0 | 14 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 1, worst post-baseline score missing | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 0, worst post-baseline score 0 | 3 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 0, worst post-baseline score 1 | 1 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 0, worst post-baseline score 2 | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 0, worst post-baseline score 3 | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 0, worst post-baseline score 4 | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 0, worst post-baseline score 5 | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 0, worst post-baseline score missing | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 1, worst post-baseline score 0 | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 1, worst post-baseline score 1 | 5 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 1, worst post-baseline score 2 | 1 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 1, worst post-baseline score 3 | 2 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 1, worst post-baseline score 4 | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 1, worst post-baseline score 5 | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Maximum Baseline score 1, worst post-baseline score missing | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 0, worst post-baseline score 0 | 4 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 0, worst post-baseline score 1 | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 0, worst post-baseline score 2 | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 0, worst post-baseline score 3 | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 0, worst post-baseline score 4 | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 0, worst post-baseline score 5 | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 0, worst post-baseline score missing | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 1, worst post-baseline score 0 | 2 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 1, worst post-baseline score 1 | 5 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 1, worst post-baseline score 2 | 1 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 1, worst post-baseline score 3 | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 1, worst post-baseline score 4 | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score | Minimum Baseline score 1, worst post-baseline score 5 | 0 Participants |
Secondary
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)
Population: Safety (SAF) analysis set included all participants who were administered any dose of any study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tepotinib + Osimertinib | Number of Participants With Markedly Abnormal Vital Sign Measurements | DBP: maximum on TR decrease of >40 mmHg | 1 Participants |
| Tepotinib + Osimertinib | Number of Participants With Markedly Abnormal Vital Sign Measurements | PR: maximum on TR increase of > 40 bpm | 4 Participants |
| Tepotinib + Osimertinib | Number of Participants With Markedly Abnormal Vital Sign Measurements | DBP: maximum on TR increase of >40 mmHg | 0 Participants |
| Tepotinib + Osimertinib | Number of Participants With Markedly Abnormal Vital Sign Measurements | PR: maximum on TR decrease of >40 bpm | 2 Participants |
| Tepotinib + Osimertinib | Number of Participants With Markedly Abnormal Vital Sign Measurements | RR: maximum on TR increase of >10 beats/min | 1 Participants |
| Tepotinib + Osimertinib | Number of Participants With Markedly Abnormal Vital Sign Measurements | BW: maximum on TR increase of >=10% | 14 Participants |
| Tepotinib + Osimertinib | Number of Participants With Markedly Abnormal Vital Sign Measurements | SBP: maximum on TR decrease of >40 mmHg | 6 Participants |
| Tepotinib + Osimertinib | Number of Participants With Markedly Abnormal Vital Sign Measurements | BW: maximum on TR decrease of >=10% | 13 Participants |
| Tepotinib + Osimertinib | Number of Participants With Markedly Abnormal Vital Sign Measurements | RR: maximum on TR decrease of >10 beats/min | 0 Participants |
| Tepotinib + Osimertinib | Number of Participants With Markedly Abnormal Vital Sign Measurements | BT: maximal on TR increase >=2 degree Celsius | 1 Participants |
| Tepotinib + Osimertinib | Number of Participants With Markedly Abnormal Vital Sign Measurements | SBP: maximum on TR increase of >40 mmHg | 2 Participants |
| Tepotinib Monotherapy | Number of Participants With Markedly Abnormal Vital Sign Measurements | BT: maximal on TR increase >=2 degree Celsius | 1 Participants |
| Tepotinib Monotherapy | Number of Participants With Markedly Abnormal Vital Sign Measurements | SBP: maximum on TR increase of >40 mmHg | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Markedly Abnormal Vital Sign Measurements | SBP: maximum on TR decrease of >40 mmHg | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Markedly Abnormal Vital Sign Measurements | DBP: maximum on TR increase of >40 mmHg | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Markedly Abnormal Vital Sign Measurements | DBP: maximum on TR decrease of >40 mmHg | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Markedly Abnormal Vital Sign Measurements | RR: maximum on TR increase of >10 beats/min | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Markedly Abnormal Vital Sign Measurements | RR: maximum on TR decrease of >10 beats/min | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Markedly Abnormal Vital Sign Measurements | PR: maximum on TR increase of > 40 bpm | 0 Participants |
| Tepotinib Monotherapy | Number of Participants With Markedly Abnormal Vital Sign Measurements | PR: maximum on TR decrease of >40 bpm | 1 Participants |
| Tepotinib Monotherapy | Number of Participants With Markedly Abnormal Vital Sign Measurements | BW: maximum on TR increase of >=10% | 1 Participants |
| Tepotinib Monotherapy | Number of Participants With Markedly Abnormal Vital Sign Measurements | BW: maximum on TR decrease of >=10% | 2 Participants |
Secondary
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)
Population: Safety (SAF) analysis set included all participants who were administered any dose of any study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tepotinib + Osimertinib | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs | TEAEs | 126 Participants |
| Tepotinib + Osimertinib | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs | Treatment-related TEAEs | 113 Participants |
| Tepotinib Monotherapy | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs | TEAEs | 12 Participants |
| Tepotinib Monotherapy | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs | Treatment-related TEAEs | 9 Participants |
Secondary
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)
Population: As per changes in planned analysis, the data for mutation status in EGFR and other pathways in ctDNA at baseline and progression were not collected with the assay used to screen for MET amplification in ctDNA.