Trial Outcomes & Findings for A Study of Tepotinib Plus Osimertinib in Osimertinib Relapsed MET Amplified NSCLC (INSIGHT 2) (NCT NCT03940703)

Last Updated: 2025-12-12

Results Overview

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.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

140 participants

Primary outcome timeframe

Up to Day 21 of Cycle 1 (each Cycle is of 21 days)

Results posted on

2025-12-12

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	128	12
Overall Study Full Analysis Set (FAS)	128	12
Overall Study Safety (SAF) Analysis Set	128	12
Overall Study Modified Full Analysis Set (mFAS)	105	12
Overall Study Safety run-in Analysis Set (SRIAS)	9	0
Overall Study Pharmacokinetic (PK) Analysis Set	120	11
Overall Study COMPLETED	97	12
Overall Study NOT COMPLETED	31	0

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Still under treatment	31	0

Baseline Characteristics

A Study of Tepotinib Plus Osimertinib in Osimertinib Relapsed MET Amplified NSCLC (INSIGHT 2)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tepotinib and Osimertinib n=128 Participants 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.	Tepotinib Mono-therapy n=12 Participants Participants received a single oral dose of Tepotinib 500 mg until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Total n=140 Participants Total of all reporting groups
Age, Continuous	59 Years STANDARD_DEVIATION 10.8 • n=26 Participants	61 Years STANDARD_DEVIATION 9.7 • n=24 Participants	60 Years STANDARD_DEVIATION 10.7 • n=50 Participants
Sex: Female, Male Female	74 Participants n=26 Participants	9 Participants n=24 Participants	83 Participants n=50 Participants
Sex: Female, Male Male	54 Participants n=26 Participants	3 Participants n=24 Participants	57 Participants n=50 Participants
Race/Ethnicity, Customized Ethnicity-Hispanic or Latino	3 Participants n=26 Participants	0 Participants n=24 Participants	3 Participants n=50 Participants
Race/Ethnicity, Customized Ethnicity-Not Hispanic or Latino	124 Participants n=26 Participants	12 Participants n=24 Participants	136 Participants n=50 Participants
Race/Ethnicity, Customized Ethnicity-Unknown or Not Reported	1 Participants n=26 Participants	0 Participants n=24 Participants	1 Participants n=50 Participants
Race/Ethnicity, Customized Race-Asian	79 Participants n=26 Participants	6 Participants n=24 Participants	85 Participants n=50 Participants
Race/Ethnicity, Customized Race-Black or African American	1 Participants n=26 Participants	0 Participants n=24 Participants	1 Participants n=50 Participants
Race/Ethnicity, Customized Race-Not Collected At This Site	4 Participants n=26 Participants	2 Participants n=24 Participants	6 Participants n=50 Participants
Race/Ethnicity, Customized Race-Other	1 Participants n=26 Participants	0 Participants n=24 Participants	1 Participants n=50 Participants
Race/Ethnicity, Customized Race-White	43 Participants n=26 Participants	4 Participants n=24 Participants	47 Participants n=50 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=9 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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	—

PRIMARY outcome

Timeframe: 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 \[T+\]).

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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=98 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 Interval 39.7 to 60.3	—

SECONDARY outcome

Timeframe: 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+).

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=31 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 Interval 36.0 to 72.7	—

SECONDARY outcome

Timeframe: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=12 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 Interval 0.2 to 38.5	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=128 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy n=12 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs TEAEs	126 Participants	12 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs Treatment-related TEAEs	113 Participants	9 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=128 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy n=12 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs Febrile neutropenia	1 Participants	0 Participants
Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs Leukopenia	1 Participants	0 Participants
Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs Alanine aminotransferase increased	2 Participants	0 Participants
Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs Alkaline phosphatase increased	1 Participants	0 Participants
Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs Myelosuppression	1 Participants	0 Participants
Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs Neutropenia	1 Participants	0 Participants
Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs Lymphocyte count decreased	1 Participants	0 Participants
Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs Neutrophil count decreased	2 Participants	0 Participants
Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs Platelet count decreased	3 Participants	0 Participants
Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs White blood cell count decreased	3 Participants	0 Participants
Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs Lipase increased	3 Participants	0 Participants
Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs Hypoalbuminemia	1 Participants	0 Participants
Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs Urinary tract infection	0 Participants	0 Participants
Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs Anemia	2 Participants	0 Participants
Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs Activated partial thromboplastin time	0 Participants	0 Participants
Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs Prothrombin international normalized ratio	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=128 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy n=12 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
Number of Participants With Markedly Abnormal Vital Sign Measurements SBP: maximum on TR increase of >40 mmHg	2 Participants	0 Participants
Number of Participants With Markedly Abnormal Vital Sign Measurements SBP: maximum on TR decrease of >40 mmHg	6 Participants	0 Participants
Number of Participants With Markedly Abnormal Vital Sign Measurements DBP: maximum on TR increase of >40 mmHg	0 Participants	0 Participants
Number of Participants With Markedly Abnormal Vital Sign Measurements DBP: maximum on TR decrease of >40 mmHg	1 Participants	0 Participants
Number of Participants With Markedly Abnormal Vital Sign Measurements RR: maximum on TR increase of >10 beats/min	1 Participants	0 Participants
Number of Participants With Markedly Abnormal Vital Sign Measurements RR: maximum on TR decrease of >10 beats/min	0 Participants	0 Participants
Number of Participants With Markedly Abnormal Vital Sign Measurements PR: maximum on TR increase of > 40 bpm	4 Participants	0 Participants
Number of Participants With Markedly Abnormal Vital Sign Measurements PR: maximum on TR decrease of >40 bpm	2 Participants	1 Participants
Number of Participants With Markedly Abnormal Vital Sign Measurements BW: maximum on TR increase of >=10%	14 Participants	1 Participants
Number of Participants With Markedly Abnormal Vital Sign Measurements BW: maximum on TR decrease of >=10%	13 Participants	2 Participants
Number of Participants With Markedly Abnormal Vital Sign Measurements BT: maximal on TR increase >=2 degree Celsius	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=128 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy n=12 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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	3 Participants
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	1 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	5 Participants
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	1 Participants
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	2 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	4 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	2 Participants
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	5 Participants
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	1 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=128 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy n=12 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings	21 Participants	1 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=98 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 Interval 34.8 to 55.3	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=98 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=98 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=49 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
Combined Therapy (Tepotinib + Osimertinib): Duration of Response Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH	8.5 months Interval 6.1 to Due to small number of events, upper limit of 95% Confidence Interval from Kaplan-Meier survival curves could not be derived.	—

SECONDARY outcome

Timeframe: From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=44 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
Combined Therapy (Tepotinib + Osimertinib): Duration of Response Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH	9.6 months Interval 7.1 to Due to small number of events, upper limit of 95% Confidence Interval from Kaplan-Meier survival curves could not be derived.	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=98 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 Interval 52.9 to 72.8	—

SECONDARY outcome

Timeframe: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=98 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
Combined Therapy (Tepotinib + Osimertinib): Disease Control Rate Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH	64.3 percentage of participants Interval 54.0 to 73.7	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=98 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 Interval 4.2 to 8.1	—

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=98 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 Interval 4.2 to 8.5	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=98 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
Combined Therapy (Tepotinib + Osimertinib): Overall Survival in Participants With MET Amplification Determined Centrally by FISH	17.8 months Interval 11.1 to Due to small number of events, upper limit of 95% confidence interval from Kaplan-Meier survival curves could not derive.	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=31 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 Interval 30.2 to 66.9	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=31 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=31 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=17 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 Interval 2.9 to 15.4	—

SECONDARY outcome

Timeframe: From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=15 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 Interval 2.9 to 9.6	—

SECONDARY outcome

Timeframe: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=31 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 Interval 45.4 to 80.8	—

SECONDARY outcome

Timeframe: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=31 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 Interval 48.6 to 83.3	—

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=31 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 Interval 2.7 to 7.2	—

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=31 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 Interval 4.2 to 7.0	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=31 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
Combined Therapy (Tepotinib + Osimertinib): Overall Survival in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing	13.7 months Interval 9.6 to Due to small number of events, upper limit of 95% confidence interval from Kaplan-Meier survival curves could not derive.	—

SECONDARY outcome

Timeframe: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=12 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 Interval 0.2 to 38.5	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=12 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=12 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 outcome

Timeframe: From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=1 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
Monotherapy (Tepotinib): Duration of Response Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH	2.8 months Insufficient number of participants with events, therefore 95% Confidence Interval could not be calculated.	—

SECONDARY outcome

Timeframe: From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=1 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
Monotherapy (Tepotinib): Duration of Response Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH	2.8 months Insufficient number of participants with events, therefore 95% Confidence Interval could not be calculated.	—

SECONDARY outcome

Timeframe: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=12 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
Monotherapy (Tepotinib): Disease Control Rate Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH	25.0 percentage of participants Interval 5.5 to 57.2	—

SECONDARY outcome

Timeframe: Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=12 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
Monotherapy (Tepotinib): Disease Control Rate Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH	25.0 percentage of participants Interval 5.5 to 57.2	—

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=12 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 Interval 1.4 to 4.4	—

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=12 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 Interval 1.4 to 4.4	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=41 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=41 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=42 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=9 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 40.0	—
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 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 40.8	—
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 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 47.1	—
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 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 50.3	—
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 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 292.6	—
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 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 624.7	—
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 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 168.9	—
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 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 41.3	—
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 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 424.6	—
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 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 54.6	—

SECONDARY outcome

Timeframe: 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.

Cmax was obtained directly from the concentration versus time curve.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=9 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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	—
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	—
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	—
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 45.0	—
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	—
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	—
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	—
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	—
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	—
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 outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tepotinib + Osimertinib n=9 Participants Participants received 500 milligrams (mg) of tepotinib orally once daily in combination with Osimertinib at a dose of 80 mg orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Tepotinib Monotherapy Participants received 500 milligrams (mg) of tepotinib orally once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
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 Interval 0.0 to 24.77	—
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 Interval 12.0 to 24.0	—
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 Interval 0.0 to 24.77	—
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 Interval 2.0 to 24.0	—
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 Interval 3.0 to 24.77	—
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 Interval 0.0 to 24.77	—
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 Interval 1.5 to 24.0	—
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 Interval 12.0 to 24.0	—
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 Interval 6.0 to 24.0	—
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 Interval 0.5 to 24.0	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Percentage of participants with resistant mutations of the EGFR gene or other pathways as assessed in ctDNA were reported.

Outcome measures

Outcome data not reported

Adverse Events

Tepotinib and Osimertinib

Serious events: 49 serious events

Other events: 123 other events

Deaths: 59 deaths

Tepotinib Mono-therapy

Serious events: 2 serious events

Other events: 12 other events

Deaths: 7 deaths

Serious adverse events

Other adverse events

Additional Information

Communication Center

Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Tepotinib and Osimertinib n=128 participants at risk 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.	Tepotinib Mono-therapy n=12 participants at risk Participants received a single oral dose of Tepotinib 500 mg until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Eye disorders Cataract	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Gastrointestinal disorders Gastric haemorrhage	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Gastrointestinal disorders Vomiting	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
General disorders Disease progression	3.9% 5/128 • Number of events 5 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
General disorders General physical health deterioration	0.00% 0/128 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	8.3% 1/12 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
General disorders Oedema peripheral	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
General disorders Pyrexia	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Hepatobiliary disorders Biliary colic	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Hepatobiliary disorders Hepatic cytolysis	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Infections and infestations COVID-19	3.9% 5/128 • Number of events 7 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Infections and infestations COVID-19 pneumonia	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Infections and infestations Carbuncle	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Infections and infestations Dengue fever	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Infections and infestations Erysipelas	1.6% 2/128 • Number of events 2 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Infections and infestations Paronychia	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Infections and infestations Pneumonia	3.9% 5/128 • Number of events 5 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Infections and infestations Upper respiratory tract infection	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Injury, poisoning and procedural complications Fall	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Injury, poisoning and procedural complications Femoral neck fracture	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Investigations Blood creatinine increased	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Investigations Ejection fraction decreased	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Investigations Neutrophil count decreased	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Investigations Platelet count decreased	2.3% 3/128 • Number of events 4 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Investigations White blood cell count decreased	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Metabolism and nutrition disorders Decreased appetite	1.6% 2/128 • Number of events 2 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Metabolism and nutrition disorders Dehydration	1.6% 2/128 • Number of events 2 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Musculoskeletal and connective tissue disorders Arthralgia	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Musculoskeletal and connective tissue disorders Neck pain	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/128 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	8.3% 1/12 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Nervous system disorders Cerebral venous sinus thrombosis	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Nervous system disorders Spinal cord compression	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Respiratory, thoracic and mediastinal disorders Aspiration	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.9% 5/128 • Number of events 5 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Respiratory, thoracic and mediastinal disorders Lung consolidation	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.9% 5/128 • Number of events 5 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Respiratory, thoracic and mediastinal disorders Pneumonitis	3.9% 5/128 • Number of events 5 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.1% 4/128 • Number of events 4 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.78% 1/128 • Number of events 1 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)	0.00% 0/12 • Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months)