Tepotinib With Gefitinib in Participants With Locally Advanced or Metastatic NSCLC (INSIGHT)

• ClinicalTrials.gov Identifier: NCT01982955
• Recruitment Status: Completed
• First Posted: November 13, 2013
• Results First Posted: July 23, 2020
• Last Update Posted: November 8, 2022
• Sponsor: Merck KGaA, Darmstadt, Germany
• Information provided by (Responsible Party): Merck KGaA, Darmstadt, Germany

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-small Cell Lung Cancer
• Interventions: Drug: Tepotinib; Drug: Gefitinib; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin
• Enrollment: 88

Participant Flow

Recruitment Details
Pre-assignment Details	A total of 18 participants were enrolled in Phase 1b part of the study and a total of 70 participants were enrolled in phase 2 part of the study. Participants enrolled in phase 1b were not eligible for randomization in phase 2.

Arm/Group Title	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg	Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)	Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)	Phase 2: Single-arm Cohort (MET+ T790M Positive)
Arm/Group Description	Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants randomized to receive Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants randomized to receive 500 milligram per square meter (mg/m^2) of Pemetrexed as intravenous infusion over 10 minutes in combination with Cisplatin (75 mg/m^2 as an intravenous infusion over 2 hours) or Carboplatin (intravenously at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator) on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment or up to 6 cycles if or 4 cycles followed by Pemetrexed maintenance monotherapy.	Participants with MET+ T790M positive Non-small Cell Lung Cancer (NSCLC) received a Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Period Title: Overall Study
Started	6	12	31	24	15
Treated	6	12	31	23	15
Completed	6	12	31	23	15
Not Completed	0	0	0	1	0
Reason Not Completed
Randomized but not treated	0	0	0	1	0

Baseline Characteristics

Arm/Group Title		Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg	Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)	Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)	Phase 2: Single-arm Cohort (MET+ T790M Positive)	Total
Arm/Group Description		Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants randomized to receive Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants randomized to receive 500 milligram per square meter (mg/m^2) of Pemetrexed as intravenous infusion over 10 minutes in combination with Cisplatin (75 mg/m^2 as an intravenous infusion over 2 hours) or Carboplatin (intravenously at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator) on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment or up to 6 cycles if or 4 cycles followed by Pemetrexed maintenance monotherapy.	Participants with MET+ T790M positive Non-small Cell Lung Cancer (NSCLC) received a Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Total of all reporting groups
Overall Number of Baseline Participants		6	12	31	24	15	88
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants	12 participants	31 participants	24 participants	15 participants	88 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	3 50.0%	6 50.0%	21 67.7%	17 70.8%	9 60.0%	56 63.6%
	>=65 years	3 50.0%	6 50.0%	10 32.3%	7 29.2%	6 40.0%	32 36.4%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants	12 participants	31 participants	24 participants	15 participants	88 participants
	Female	3 50.0%	7 58.3%	20 64.5%	12 50.0%	10 66.7%	52 59.1%
	Male	3 50.0%	5 41.7%	11 35.5%	12 50.0%	5 33.3%	36 40.9%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants	12 participants	31 participants	24 participants	15 participants	88 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	6 100.0%	12 100.0%	31 100.0%	24 100.0%	15 100.0%	88 100.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	White	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Phase 1b: Number of Participants Experiencing at Least One Dose Limiting Toxicity (DLT)
Description	Dose limiting toxicity (DLT) using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0 was defined as toxicities at any dose level and judged to be related to the study treatment by investigator and/or the sponsor. DLTs included Grade 4 neutropenia for more than 7 days; Grade greater than or equal to (>=) 3 febrile neutropenia for more than 1 day; Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with non-traumatic bleeding; Grade >= 3 uncontrolled nausea/vomiting and/or diarrhea despite adequate and optimal treatment and Grade >= 3 any non-hematological adverse event (AE), except the aforementioned gastrointestinal events and alopecia. Number of participants who experienced DLT during Phase 1b were reported.
Time Frame	Day 1 to Day 21 of Cycle 1 (each cycle is 21 days)

Outcome Measure Data

Analysis Population Description

Dose Limiting Toxicity (DLT) set included all participants who experienced a DLT during Cycle 1, or received at least 80 percent of all planned doses of treatment during Cycle.

Arm/Group Title	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:	Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	3	12
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%

2. Primary Outcome

Title	Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Description	An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious TEAEs and non-serious TEAEs. Number of Participants with TEAEs and serious TEAEs were reported.
Time Frame	Up to 175 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:	Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	6	12
Measure Type: Count of Participants; Unit of Measure: Participants
Any TEAEs	6 100.0%	12 100.0%
Any Serious TEAEs	4 66.7%	7 58.3%

3. Primary Outcome

Title	Phase 2 (Randomized Part Only): Progression-free Survival (PFS) Based on Tumor Assessment by the Investigator
Description	Progression-free survival (assessed by the Investigator) time was defined as the time in months from randomization to either first observation of radiologically confirmed progression disease (PD) by the investigator or occurrence of death due to any cause within 84 days of either randomization or the last tumor assessment. PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 millimeter (mm). PFS was measured using Kaplan-Meier (KM) estimates.
Time Frame	Up to 328 weeks

Outcome Measure Data

Analysis Population Description

The Intent-to-treat analysis set in the Phase 2 part of the study included all participants with treatment group who were randomized to study treatment.

Arm/Group Title	Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)	Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)
Arm/Group Description:	Participants randomized to receive Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants randomized to receive 500 milligram per square meter (mg/m^2) of Pemetrexed as intravenous infusion over 10 minutes in combination with Cisplatin (75 mg/m^2 as an intravenous infusion over 2 hours) or Carboplatin (intravenously at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator) on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment or up to 6 cycles if or 4 cycles followed by Pemetrexed maintenance monotherapy.
Overall Number of Participants Analyzed	31	24
Median (90% Confidence Interval); Unit of Measure: Months
	4.86; (3.88 to 6.87)	4.37; (4.17 to 6.80)

4. Secondary Outcome

Title	Phase 1b: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time AUC (0-t) of Tepotinib, Its Metabolites and Gefitinib
Description	Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration is at or above the lower limit of quantification (LLLQ). AUC(0-t) was calculated according to the mixed log-linear trapezoidal rule.
Time Frame	Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic (PK) set included all participants who had received at least 1 dose of the tepotinib or gefitinib and who had provided at least 1 plasma concentration measurement of tepotinib or gefitinib after the first dose. Here "Number Analyzed" signifies those participants who were evaluable for specified category.

Arm/Group Title		Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:		Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed		6	12
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanogram*hour per milliliter (ng*h/mL)
Tepotinib: Day 1 of Cycle 1	Number Analyzed	5 participants	12 participants
		6280; (25.4%)	9210; (48.4%)
Tepotinib: Day 15 of Cycle 1	Number Analyzed	6 participants	9 participants
		15600; (19.6%)	22200; (43.3%)
MSC2571109A: Day 1 of Cycle 1	Number Analyzed	5 participants	11 participants
		1680; (11.8%)	1770; (56.7%)
MSC2571109A Day15 of Cycle 1	Number Analyzed	6 participants	8 participants
		4420; (25.7%)	7530; (52.6%)
MSC2571107A Day 1 of Cycle 1	Number Analyzed	5 participants	11 participants
		248; (49.3%)	324; (57.3%)
MSC2571107A Day 15 of Cycle 1	Number Analyzed	6 participants	8 participants
		872; (38.5%)	1880; (76.0%)
Gefitinib: Day 1 of Cycle 1	Number Analyzed	2 participants	11 participants
		NA [1]; (NA%)	2930; (45.8%)
Gefitinib: Day 15 of Cycle 1	Number Analyzed	6 participants	9 participants
		7690; (44.1%)	7080; (29.0%)

[1]

Only 2 participants had evaluable AUC(0-t) at time point. For statistical reasons, calculation of summary statistics does not make sense for this low sample size. Individual values were 3830 and 3980 ng*h/mL.

5. Secondary Outcome

Title	Phase 1b: Area Under the Plasma Concentration-Time Curve Within 1 Dosing Interval (AUC 0-tau) of Tepotinib, Its Metabolites and Gefitinib
Description	AUC (0-tau) is the area under the plasma concentration time curve within 1 dosing interval.
Time Frame	Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

Outcome Measure Data

Analysis Population Description

The PK set included all participants who had received at least 1 dose of the tepotinib or gefitinib and who had provided at least 1 plasma concentration measurement of tepotinib or gefitinib after the first dose. Here "Number Analyzed" signifies those participants who were evaluable for specified category.

Arm/Group Title		Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:		Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed		6	12
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng*h/mL
Tepotinib: Day 1 of Cycle 1	Number Analyzed	5 participants	12 participants
		6280; (25.4%)	9210; (48.4%)
Tepotinib: Day 15 of Cycle 1	Number Analyzed	6 participants	9 participants
		15600; (19.6%)	22200; (43.3%)
MSC2571109A: Day 1 of Cycle 1	Number Analyzed	5 participants	11 participants
		1680; (11.8%)	1770; (56.7%)
MSC2571109A: Day 15 of Cycle 1	Number Analyzed	6 participants	8 participants
		4420; (25.7%)	7530; (52.6%)
MSC2571107A: Day 1 of Cycle 1	Number Analyzed	5 participants	11 participants
		248; (49.3%)	324; (57.3%)
MSC2571107A: Day 15 of Cycle 1	Number Analyzed	6 participants	8 participants
		872; (38.5%)	1880; (76.0%)
Gefitinib: Day 1 of Cycle 1	Number Analyzed	2 participants	11 participants
		NA [1]; (NA%)	2930; (45.8%)
Gefitinib: Day 15 of Cycle 1	Number Analyzed	6 participants	9 participants
		7690; (44.1%)	7080; (29.0%)

[1]

Only 2 participants had evaluable AUC(0-tau) at time point. For statistical reasons, calculation of summary statistics does not make sense for this low sample size. Individual values were 3830 and 3980 ng*h/mL.

6. Secondary Outcome

Title	Phase 1b: Maximum Observed Plasma Concentration (Cmax) of Tepotinib, Its Metabolites and Gefitinib
Description	Cmax is the maximum observed plasma concentration obtained directly from the concentration versus time curve.
Time Frame	Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

Outcome Measure Data

Analysis Population Description

The PK set included all participants who had received at least 1 dose of the tepotinib or gefitinib and who had provided at least 1 plasma concentration measurement of tepotinib or gefitinib after the first dose. Here "Number Analyzed" signifies those participants who were evaluable for specified category.

Arm/Group Title		Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:		Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed		6	12
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Nanogram per Milliliter (ng/mL)
Tepotinib: Day 1 of Cycle 1	Number Analyzed	5 participants	12 participants
		375; (30.4%)	575; (62.6%)
Tepotinib: Day 15 of Cycle 1	Number Analyzed	6 participants	10 participants
		763; (22.0%)	1050; (44.1%)
MSC2571109A: Day 1 of Cycle 1	Number Analyzed	5 participants	11 participants
		132; (14.7%)	149; (56.5%)
MSC2571109A: Day 15 of Cycle 1	Number Analyzed	6 participants	9 participants
		280; (32.0%)	444; (45.8%)
MSC2571107A: Day 1 of Cycle 1	Number Analyzed	5 participants	11 participants
		16.8; (56.5%)	24.3; (62.5%)
MSC2571107A: Day 15 of Cycle 1	Number Analyzed	6 participants	9 participants
		44.9; (40.5%)	94.9; (70.8%)
Gefitinib: Day 1 of Cycle 1	Number Analyzed	2 participants	11 participants
		NA [1]; (NA%)	215; (48.7%)
Gefitinib: Day 15 of Cycle 1	Number Analyzed	6 participants	10 participants
		432; (38.3%)	366; (32.6%)

[1]

Only 2 participants had evaluable Cmax at time point. For statistical reasons, calculation of summary statistics does not make sense for this low sample size. Individual values were 302 and 305 ng/mL.

7. Secondary Outcome

Title	Phase 1b: Average Observed Plasma Concentration (Cavg) of Tepotinib, Its Metabolites and Gefitinib
Description	Cavg is the average plasma concentration within 1 dosing interval obtained directly from the concentration versus time curve.
Time Frame	Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 15 of Cycle 1 (each Cycle is 21 days)

Outcome Measure Data

Analysis Population Description

The PK analysis set employed here. "Number of participants analyzed" signifies participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable for specified category.

Arm/Group Title		Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:		Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed		6	9
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
Tepotinib	Number Analyzed	6 participants	9 participants
		654; (19.4%)	924; (43.3%)
MSC2571109A	Number Analyzed	6 participants	8 participants
		185; (25.4%)	314; (52.6%)
MSC2571107A	Number Analyzed	6 participants	8 participants
		36.4; (38.2%)	78.3; (76.0%)
Gefitinib	Number Analyzed	6 participants	9 participants
		321; (43.9%)	295; (29.0%)

8. Secondary Outcome

Title	Phase 1b: Minimum Observed Plasma Concentration (Cmin) of Tepotinib, Its Metabolites and Gefitinib
Description	Cmin is minimum observed plasma concentration obtained directly from the concentration versus time curve.
Time Frame	Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 15 of Cycle 1 (each Cycle is 21 days)

Outcome Measure Data

Analysis Population Description

The PK analysis set employed here. "Number of participants analyzed" signifies participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable for specified category.

Arm/Group Title		Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:		Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed		6	9
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
Tepotinib	Number Analyzed	6 participants	9 participants
		534; (18.8%)	735; (47.6%)
MSC2571109A	Number Analyzed	6 participants	8 participants
		156; (28.8%)	270; (58.5%)
MSC2571107A	Number Analyzed	6 participants	8 participants
		32.8; (40.1%)	68.7; (80.1%)
Geftinib	Number Analyzed	6 participants	9 participants
		231; (57.3%)	190; (43.5%)

9. Secondary Outcome

Title	Phase 1b: Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib, Its Metabolites and Gefitinib
Description	Tmax is time to reach maximum observed plasma concentration obtained directly from the concentration versus time curve.
Time Frame	Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic set included all participants who had received at least 1 dose of the tepotinib or gefitinib and who had provided at least 1 plasma concentration measurement of tepotinib or gefitinib after the first dose. Here "Number Analyzed" signifies those participants who were evaluable for specified category.

Arm/Group Title		Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:		Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed		6	12
Median (Full Range); Unit of Measure: Hours
Tepotinib: Day 1 of Cycle 1	Number Analyzed	5 participants	12 participants
		8.00; (4.00 to 8.00)	9.01; (4.00 to 10.00)
Tepotinib: Day 15 of Cycle 1	Number Analyzed	6 participants	10 participants
		6.00; (0.00 to 8.00)	9.00; (4.00 to 24.00)
MSC2571109A: Day 1 of Cycle 1	Number Analyzed	5 participants	11 participants
		24.00; (23.75 to 24.00)	24.00; (24.00 to 24.00)
MSC2571109A: Day 15 of Cycle 1	Number Analyzed	6 participants	9 participants
		0.00; (0.00 to 24.00)	0.00; (0.00 to 24.00)
MSC2571107A: Day 1 of Cycle 1	Number Analyzed	5 participants	11 participants
		24.00; (23.75 to 24.00)	24.00; (24.00 to 24.00)
MSC2571107A: Day 15 of Cycle 1	Number Analyzed	6 participants	9 participants
		0.13; (0.00 to 8.00)	0.25; (0.00 to 24.00)
Gefitinib: Day 1 of Cycle 1	Number Analyzed	2 participants	11 participants
		NA [1]; (NA to NA)	8.00; (4.00 to 8.02)
Gefitinib: Day 15 of Cycle 1	Number Analyzed	6 participants	10 participants
		4.00; (4.00 to 10.00)	8.00; (4.00 to 10.12)

[1]

Only 2 participants had evaluable tmax at time point. For statistical reasons, calculation of summary statistics does not make sense for this low sample size. Individual values were 4.00 and 4.00 hour.

10. Secondary Outcome

Title	Phase 1b: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC 0-infinity) of Tepotinib, Its Metabolites and Gefitinib
Description	The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
Time Frame	Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic set included all participants who had received at least 1 dose of the tepotinib or gefitinib and who had provided at least 1 plasma concentration measurement of tepotinib or gefitinib after the first dose.

Arm/Group Title	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:	Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	6	12
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng*h/mL
Tepotinib: Day 1 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
Tepotinib: Day 15 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
MSC2571109A: Day 1 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
MSC2571109A: Day 15 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
MSC2571107A: Day 1 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
MSC2571107A: Day 15 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
Gefitinib: Day 1 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
Gefitinib: Day 15 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)

[1]

Study drug administered once daily with rich PK sampling up to 24 hours. As half-life of study drug exceeding the PK sampling time, Lambda(z) could not be reliably estimated. Therefore, AUC(0-inf) which is dependent on Lambda(z) was not determined.

11. Secondary Outcome

Title	Phase 1b: Apparent Total Body Clearance From Plasma (CL/F) of Tepotinib and Gefitinib
Description	The CL/f is a measure of the rate at which it was metabolized or eliminated by normal biological processes. Clearance obtained after oral dose was influenced by the fraction of the dose absorbed. The CL/F from plasma was calculated using the formula: Dose divided by area under the concentration time curve from time zero to infinity (AUC0-inf).
Time Frame	Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 15 of Cycle 1 (each Cycle is 21 days)

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic set included all participants who had received at least 1 dose of the tepotinib or gefitinib and who had provided at least 1 plasma concentration measurement of tepotinib or gefitinib after the first dose. Here, "Number of participants analyzed" signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:	Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	6	9
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: liter per hour (L/h)
Tepotinib	17.3; (19.6%)	20.3; (43.3%)
Gefitinib	32.5; (44.1%)	35.3; (29.0%)

12. Secondary Outcome

Title	Phase 1b: Apparent Volume of Distribution (Vz/F) During the Terminal Phase of Tepotinib, Its Metabolites and Gefitinib
Description	The Vz/f was defined as the theoretical volume in which the total amount of required to uniformly distribute to produce the desired plasma concentration. Apparent volume of distribution after oral dose (Vz/F) was influenced by the fraction absorbed. The Vz/f was calculated by dividing the dose with area under the concentration time curve from time zero to infinity multiplied with terminal elimination rate constant Lambda(z). Vz/f=Dose/AUC(0-inf) multiply Lambda(z).
Time Frame	Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic set included all participants who had received at least 1 dose of the tepotinib or gefitinib and who had provided at least 1 plasma concentration measurement of tepotinib or gefitinib after the first dose.

Arm/Group Title	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:	Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	6	12
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Liter
Tepotinib: Day 1 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
Tepotinib: Day 15 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
MSC2571109A: Day 1 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
MSC2571109A: Day 15 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
MSC2571107A: Day 1 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
MSC2571107A: Day 15 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
Gefitinib: Day 1 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
Gefitinib: Day 15 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)

[1]

Study drug administered once daily with rich PK sampling up to 24 hours. As half-life of study drug exceeding the PK sampling time, Lambda(z) could not be reliably estimated. Therefore, Vz/F which is dependent on Lambda(z) was not determined.

13. Secondary Outcome

Title	Phase 1b: Apparent Volume of Distribution During the Steady State (Vss/F) of Tepotinib, Its Metabolites and Gefitinib
Description	Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss/f after oral dose was influenced by the fraction absorbed.
Time Frame	Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic set included all participants who had received at least 1 dose of the tepotinib or gefitinib and who had provided at least 1 plasma concentration measurement of tepotinib or gefitinib after the first dose.

Arm/Group Title	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:	Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	6	12
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Liter
Tepotinib: Day 1 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
Tepotinib: Day 15 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
MSC2571109A: Day 1 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
MSC2571109A: Day 15 of cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
MSC2571107A: Day 1 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
MSC2571107A: Day 15 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
Gefitinib: Day 1 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
Gefitinib: Day 15 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)

[1]

Study drug administered once daily with rich PK sampling up to 24 hours. As half-life of study drug exceeding the PK sampling time, Lambda(z) could not be reliably estimated. Therefore, Vss/F which is dependent on Lambda(z) was not determined.

14. Secondary Outcome

Title	Phase 1b: Apparent Terminal Elimination Rate Constant Lambda(z) of Tepotinib, Its Metabolites and Gefitinib
Description	Lambda(z) was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
Time Frame	Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic set included all participants who had received at least 1 dose of the tepotinib or gefitinib and who had provided at least 1 plasma concentration measurement of tepotinib or gefitinib after the first dose.

Arm/Group Title	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:	Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	6	12
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 1 per hour
Tepotinib: Day 1 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
Tepotinib: Day 15 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
MSC2571109A: Day 1 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
MSC2571109A: Day 15 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
MSC2571107A: Day 1 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
MSC2571107A: Day 15 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
Gefitinib: Day 1 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)
Gefitinib: Day 15 of Cycle 1	NA [1]; (NA%)	NA [1]; (NA%)

[1]

Study drug administered once daily with rich PK sampling up to 24 hours. As half-life of study drug exceeding the PK sampling time, Lambda(z) could not be reliably estimated. Therefore, Lambda (z) was not determined.

15. Secondary Outcome

Title	Phase 1b: Apparent Terminal Half-Life (t1/2) of Tepotinib, Its Metabolites and Gefitinib
Description	Apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination.
Time Frame	Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic set included all participants who had received at least 1 dose of the tepotinib or gefitinib and who had provided at least 1 plasma concentration measurement of tepotinib or gefitinib after the first dose.

Arm/Group Title	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:	Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	6	12
Median (Full Range); Unit of Measure: Hours
Tepotinib: Day 1 of Cycle 1	NA [1]; (NA to NA)	NA [1]; (NA to NA)
Tepotinib: Day 15 of Cycle 1	NA [1]; (NA to NA)	NA [1]; (NA to NA)
MSC2571109A: Day 1 of Cycle 1	NA [1]; (NA to NA)	NA [1]; (NA to NA)
MSC2571109A: Day 15 of Cycle 1	NA [1]; (NA to NA)	NA [1]; (NA to NA)
MSC2571107A: Day 1 of Cycle 1	NA [1]; (NA to NA)	NA [1]; (NA to NA)
MSC2571107A: Day 15 of Cycle 1	NA [1]; (NA to NA)	NA [1]; (NA to NA)
Gefitinib: Day 1 of Cycle 1	NA [1]; (NA to NA)	NA [1]; (NA to NA)
Gefitinib: Day 15 of Cycle 1	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

Study drug administered once daily with rich PK sampling up to 24 hours. As half-life of study drug exceeding the PK sampling time, Lambda(z) could not be reliably estimated. Therefore, t1/2 which is dependent on Lambda(z) was not determined.

16. Secondary Outcome

Title	Phase 1b: Percentage of Participants With Objective Response Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria
Description	Objective response (OR) was defined as the percentage of participants who had achieved complete response (CR) or partial response (PR) as the best overall response according to local radiological assessments from randomization/the first administration of the study treatment to the first observation of disease progression (PD). CR: defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame	Up to 328 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:	Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	6	12
Measure Type: Number; Number (90% Confidence Interval); Unit of Measure: Percentage of Participants
	33.3; (6.3 to 72.9)	33.3; (12.3 to 60.9)

17. Secondary Outcome

Title	Phase 1b: Percentage of Participants With Disease Control Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria
Description	Disease control defined as CR, PR, or stable disease(SD) as the best overall response according to local radiological assessments from the date of randomization/the first administration of the study treatment to the first observation of PD. CR:disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR:at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD:an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5mm. SD:as any cases that do not qualify for either PR or PD at minimum interval of 42 days after randomization/start of study treatment
Time Frame	Up to 328 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:	Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	6	12
Measure Type: Number; Number (90% Confidence Interval); Unit of Measure: Percentage of Participants
	50.0; (15.3 to 84.7)	58.3; (31.5 to 81.9)

18. Secondary Outcome

Title	Phase 1b: Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Serious TEAEs According to National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03
Description	An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Term TEAE was defined as AEs starting/worsening after first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs. Treatment-related AE was defined as having a "Possible" or "Related" relationship to study treatment, as assessed by the Investigator.
Time Frame	Up to 175 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:	Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	6	12
Measure Type: Count of Participants; Unit of Measure: Participants
Any TEAE Related to Tepotinib	6 100.0%	9 75.0%
Any TEAE Related to Gefitinib	5 83.3%	11 91.7%
Any Serious TEAE Related to Tepotinib	0 0.0%	0 0.0%
Any Serious TEAE Related to Gefitinib	0 0.0%	0 0.0%

19. Secondary Outcome

Title	Phase 1b: Number of Participants With Grade 3/4 Treatment-Emergent Adverse Events (TEAEs) and Grade 3/4 Treatment-Related TEAEs According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 4.03
Description	An adverse event (AE) was defined as any untoward medical occurrence in participant which does not necessarily have casual relationship with treatment was any unfavorable and unintended sign(including abnormal laboratory finding), symptom/disease temporally associated with use of medicinal product, whether/not considered related to medicinal product. Term TEAE was defined as AEs starting/worsening after first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs. Treatment-related TEAE was defined as having a "Possible" or "Related" relationship to study treatment, as assessed by the Investigator. As per NCI-CTCAE, Grade 3 is Severe, Grade 4 is Life-threatening and Grade 5 or Death. Number of participants with Grade 3/4 TEAEs and Grade 3/4 treatment-related TEAEs were reported.
Time Frame	Up to 175 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:	Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	6	12
Measure Type: Count of Participants; Unit of Measure: Participants
Any Grade 3/4 TEAE	5 83.3%	9 75.0%
Any Grade 3/4 TEAE Related to Tepotinib	2 33.3%	4 33.3%
Any Grade 3/4 TEAE Related to Gefitinib	0 0.0%	0 0.0%

20. Secondary Outcome

Title	Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Permanent Treatment Discontinuation
Description	An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Term TEAE is defined as AEs starting/worsening after first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs. Number of participants with TEAEs leading to permanent treatment discontinuation were reported.
Time Frame	Up to 175 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:	Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	6	12
Measure Type: Count of Participants; Unit of Measure: Participants
TEAE Leading Permanent Tepotinib Discontinuation	0 0.0%	2 16.7%
TEAE Leading Permanent Gefitinib Discontinuation	0 0.0%	1 8.3%

21. Secondary Outcome

Title	Phase 1b: Number of Participants With Death and Reasons
Description	Number of participants with death due to progressive disease (PD), adverse event (AE) related to study treatment, AE not related to study treatment were reported. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. PD defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm. Number of participants with deaths due to PD, AE related to study treatment, AE not related to study treatment were reported.
Time Frame	Up to 175 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:	Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	6	12
Measure Type: Count of Participants; Unit of Measure: Participants
Death due to PD	0 0.0%	3 25.0%
Death due to AE related to study treatment	0 0.0%	0 0.0%
Death due to AE not related to study treatment	1 16.7%	0 0.0%

22. Secondary Outcome

Title	Phase 1b: Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI-CTCAE Version 4.03 Reported as Treatment-Emergent Adverse Events (TEAEs)
Description	The laboratory measurements included hematology and coagulation, biochemistry and urinalysis.
Time Frame	Up to 175 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:	Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	6	12
Measure Type: Count of Participants; Unit of Measure: Participants
Amylase increased	2 33.3%	2 16.7%
Lipase increased	1 16.7%	2 16.7%
Neutrophil count decreased	0 0.0%	1 8.3%
Hyperglycemia	0 0.0%	2 16.7%
Hypocalcemia	1 16.7%	0 0.0%
Hyponatremia	0 0.0%	2 16.7%
Hypoproteinemia	1 16.7%	0 0.0%

23. Secondary Outcome

Title	Phase 1b: Number of Participants With Clinically Significant Abnormalities in Vital Signs
Description	Vital signs assessment included blood pressure, heart rate, respiratory rate and body temperature. Number of Participants with any clinically significant abnormalities in vital signs were reported. Clinical significance was determined by the investigator.
Time Frame	Up to 175 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:	Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	6	12
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%

24. Secondary Outcome

Title	Phase 1b: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiograms (ECG) Findings
Description	ECG parameters included heart rhythm, pulse rate intervals, QRS, QT intervals, RR intervals and corrected QT(QTc) intervals. Clinical significance was determined by the investigator. Number of participants with clinically significant abnormalities in 12-lead ECG were reported.
Time Frame	Up to 175 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:	Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	6	12
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%

25. Secondary Outcome

Title	Phase 1b: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 2 or Higher Than 2
Description	ECOG PS score is widely used by doctors and researchers to assess how a participants' disease is progressing, and is used to assess how the disease affects the daily living abilities of the participant, and determine appropriate treatment and prognosis. The score ranges from Grade 0 to Grade 5, where Grade 0 = Fully active, able to carry on all pre-disease performance without restriction, Grade 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (like light house work, office work), Grade 2 = Ambulatory and capable of all self-care but unable to carry out any work activities, Grade 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours and Grade 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair, Grade 5 = Death. Number of participants with ECOG performance status score of 2 or higher than 2 were reported.
Time Frame	Up to 175 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg
Arm/Group Description:	Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	6	12
Measure Type: Count of Participants; Unit of Measure: Participants
	1 16.7%	9 75.0%

26. Secondary Outcome

Title	Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-Related TEAEs and Treatment-Related Serious TEAEs According to National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03
Description	An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs was defined as AEs that started or worsened in severity within the first dosing day of study treatment after the last dose of study treatment. TEAEs include both Serious TEAEs and non-serious TEAEs Treatment related AE was defined as having a "Possible" or "Related" relationship to study treatment, as assessed by the Investigator.
Time Frame	Up to 328 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)	Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)	Phase 2: Single-arm Cohort (MET+ T790M Positive)
Arm/Group Description:	Participants randomized to receive Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants randomized to receive 500 milligram per square meter (mg/m^2) of Pemetrexed as intravenous infusion over 10 minutes in combination with Cisplatin (75 mg/m^2 as an intravenous infusion over 2 hours) or Carboplatin (intravenously at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator) on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment or up to 6 cycles if or 4 cycles followed by Pemetrexed maintenance monotherapy.	Participants with MET+ T790M positive Non-small Cell Lung Cancer (NSCLC) received a Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	31	23	15
Measure Type: Count of Participants; Unit of Measure: Participants
Any TEAE	31 100.0%	23 100.0%	13 86.7%
Any Treatment-Related TEAE	30 96.8%	23 100.0%	11 73.3%
Any Serious TEAE	13 41.9%	8 34.8%	5 33.3%
Any Treatment-Related Serious TEAE	6 19.4%	7 30.4%	1 6.7%

27. Secondary Outcome

Title	Phase 2: Number of Participants With Greater Than or Equal to (>=) Grade 3 Treatment-Emergent Adverse Events (TEAEs) and >= Grade 3 Treatment-Related TEAEs According to National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03
Description	An adverse event (AE) was defined as any untoward medical occurrence in participant which does not necessarily have casual relationship with treatment was any unfavorable and unintended sign(including abnormal laboratory finding), symptom/disease temporally associated with use of medicinal product, whether/not considered related to medicinal product. Term TEAE is defined as AEs starting/worsening after first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs. Treatment-related AE was defined as having a "Possible" or "Related" relationship to study treatment, as assessed by the Investigator. As per NCI-CTCAE, Grade 3 is Severe, Grade 4 is Life-threatening and Grade 5 or Death. Number of Participants With >= Grade 3 TEAEs and >= Grade 3 treatment-related TEAEs were reported.
Time Frame	Up to 328 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)	Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)	Phase 2: Single-arm Cohort (MET+ T790M Positive)
Arm/Group Description:	Participants randomized to receive Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants randomized to receive 500 milligram per square meter (mg/m^2) of Pemetrexed as intravenous infusion over 10 minutes in combination with Cisplatin (75 mg/m^2 as an intravenous infusion over 2 hours) or Carboplatin (intravenously at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator) on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment or up to 6 cycles if or 4 cycles followed by Pemetrexed maintenance monotherapy.	Participants with MET+ T790M positive Non-small Cell Lung Cancer (NSCLC) received a Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	31	23	15
Measure Type: Count of Participants; Unit of Measure: Participants
Any TEAE of >= Grade 3	20 64.5%	14 60.9%	7 46.7%
Any Treatment-related TEAE of >= Grade 3	16 51.6%	12 52.2%	1 6.7%

28. Secondary Outcome

Title	Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Permanent Treatment Discontinuation
Description	An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Term TEAE is defined as AEs starting/worsening after first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs. Number of participants with TEAEs leading to permanent treatment discontinuation were reported.
Time Frame	Up to 328 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)	Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)	Phase 2: Single-arm Cohort (MET+ T790M Positive)
Arm/Group Description:	Participants randomized to receive Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants randomized to receive 500 milligram per square meter (mg/m^2) of Pemetrexed as intravenous infusion over 10 minutes in combination with Cisplatin (75 mg/m^2 as an intravenous infusion over 2 hours) or Carboplatin (intravenously at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator) on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment or up to 6 cycles if or 4 cycles followed by Pemetrexed maintenance monotherapy.	Participants with MET+ T790M positive Non-small Cell Lung Cancer (NSCLC) received a Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	31	23	15
Measure Type: Count of Participants; Unit of Measure: Participants
	3 9.7%	1 4.3%	2 13.3%

29. Secondary Outcome

Title	Phase 2: Number of Participants With Death and Reasons
Description	An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. PD defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm. Number of participants with deaths due to progression disease (PD), AE related to study treatment, unknown reason was reported.
Time Frame	Up to 328 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)	Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)	Phase 2: Single-arm Cohort (MET+ T790M Positive)
Arm/Group Description:	Participants randomized to receive Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants randomized to receive 500 milligram per square meter (mg/m^2) of Pemetrexed as intravenous infusion over 10 minutes in combination with Cisplatin (75 mg/m^2 as an intravenous infusion over 2 hours) or Carboplatin (intravenously at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator) on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment or up to 6 cycles if or 4 cycles followed by Pemetrexed maintenance monotherapy.	Participants with MET+ T790M positive Non-small Cell Lung Cancer (NSCLC) received a Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	31	23	15
Measure Type: Count of Participants; Unit of Measure: Participants
Death due to disease progression	21 67.7%	15 65.2%	8 53.3%
Death due to AE related to study treatment	0 0.0%	0 0.0%	0 0.0%
Death due to unknown reason	2 6.5%	5 21.7%	2 13.3%

30. Secondary Outcome

Title	Phase 2: Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI-CTCAE Version 4.03 Reported as Treatment-Emergent Adverse Events (TEAEs)
Description	The laboratory measurements included hematology and coagulation, biochemistry and urinalysis.
Time Frame	Up to 328 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)	Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)	Phase 2: Single-arm Cohort (MET+ T790M Positive)
Arm/Group Description:	Participants randomized to receive Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants randomized to receive 500 milligram per square meter (mg/m^2) of Pemetrexed as intravenous infusion over 10 minutes in combination with Cisplatin (75 mg/m^2 as an intravenous infusion over 2 hours) or Carboplatin (intravenously at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator) on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment or up to 6 cycles if or 4 cycles followed by Pemetrexed maintenance monotherapy.	Participants with MET+ T790M positive Non-small Cell Lung Cancer (NSCLC) received a Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	31	23	15
Measure Type: Count of Participants; Unit of Measure: Participants
Anaemia	0 0.0%	7 30.4%	0 0.0%
Neutropenia	0 0.0%	1 4.3%	0 0.0%
Alanine aminotransferase increased	1 3.2%	0 0.0%	0 0.0%
Amylase increased	7 22.6%	2 8.7%	2 13.3%
Gamma-glutamyltransferase increased	0 0.0%	1 4.3%	0 0.0%
Lipase increased	5 16.1%	2 8.7%	1 6.7%
Neutrophil count decreased	2 6.5%	3 13.0%	0 0.0%
White blood cell count decreased	1 3.2%	2 8.7%	0 0.0%
Hyponatremia	1 3.2%	3 13.0%	0 0.0%
Hypokalemia	0 0.0%	2 8.7%	0 0.0%
hypophosphatemia	0 0.0%	1 4.3%	0 0.0%
Hypoalbuminemia	1 3.2%	0 0.0%	0 0.0%

31. Secondary Outcome

Title	Phase 2: Number of Participants With Clinically Significant Abnormalities in Vital Signs
Description	Vital signs assessment included blood pressure, heart rate, respiratory rate and body temperature. Number of Participants with any clinically significant abnormalities in vital signs were reported. Clinical significance was determined by the investigator.
Time Frame	Up to 328 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)	Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)	Phase 2: Single-arm Cohort (MET+ T790M Positive)
Arm/Group Description:	Participants randomized to receive Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants randomized to receive 500 milligram per square meter (mg/m^2) of Pemetrexed as intravenous infusion over 10 minutes in combination with Cisplatin (75 mg/m^2 as an intravenous infusion over 2 hours) or Carboplatin (intravenously at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator) on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment or up to 6 cycles if or 4 cycles followed by Pemetrexed maintenance monotherapy.	Participants with MET+ T790M positive Non-small Cell Lung Cancer (NSCLC) received a Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	31	23	15
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%	0 0.0%

32. Secondary Outcome

Title	Phase 2: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiograms (ECG) Findings
Description	ECG parameters included heart rhythm, pulse rate intervals, QRS, QT intervals, RR intervals and corrected QT(QTc) intervals. Clinical significance was determined by the investigator. Number of participants with clinically significant abnormalities in 12-lead ECG were reported.
Time Frame	Up to 328 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)	Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)	Phase 2: Single-arm Cohort (MET+ T790M Positive)
Arm/Group Description:	Participants randomized to receive Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants randomized to receive 500 milligram per square meter (mg/m^2) of Pemetrexed as intravenous infusion over 10 minutes in combination with Cisplatin (75 mg/m^2 as an intravenous infusion over 2 hours) or Carboplatin (intravenously at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator) on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment or up to 6 cycles if or 4 cycles followed by Pemetrexed maintenance monotherapy.	Participants with MET+ T790M positive Non-small Cell Lung Cancer (NSCLC) received a Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	31	23	15
Measure Type: Count of Participants; Unit of Measure: Participants
	2 6.5%	1 4.3%	0 0.0%

33. Secondary Outcome

Title	Phase 2: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 2 or Higher Than 2
Description	ECOG PS score is widely used by doctors and researchers to assess how a participants' disease is progressing, and is used to assess how the disease affects the daily living abilities of the participant, and determine appropriate treatment and prognosis. The score ranges from Grade 0 to Grade 5, where Grade 0 = Fully active, able to carry on all pre-disease performance without restriction, Grade 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (like light house work, office work), Grade 2 = Ambulatory and capable of all self-care but unable to carry out any work activities, Grade 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours and Grade 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair, Grade 5 = Death. Number of participants with ECOG performance status score of 2 or higher than 2 were reported.
Time Frame	Up to 328 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)	Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)	Phase 2: Single-arm Cohort (MET+ T790M Positive)
Arm/Group Description:	Participants randomized to receive Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants randomized to receive 500 milligram per square meter (mg/m^2) of Pemetrexed as intravenous infusion over 10 minutes in combination with Cisplatin (75 mg/m^2 as an intravenous infusion over 2 hours) or Carboplatin (intravenously at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator) on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment or up to 6 cycles if or 4 cycles followed by Pemetrexed maintenance monotherapy.	Participants with MET+ T790M positive Non-small Cell Lung Cancer (NSCLC) received a Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	31	23	15
Measure Type: Count of Participants; Unit of Measure: Participants
	6 19.4%	1 4.3%	1 6.7%

34. Secondary Outcome

Title	Phase 2 (Randomized Part Only): Progression-free Survival (PFS) Based on Tumor Assessment by Independent Review Committee (IRC)
Description	Progression-free survival (assessed by Independent Review Committee) time was defined as the time in months from randomization to either first observation of radiologically confirmed progression disease (PD) by the IRC or occurrence of death due to any cause within 84 days of either randomization or the last tumor assessment. PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm. PFS was measured using Kaplan-Meier (KM) estimates.
Time Frame	Up to 328 weeks

Outcome Measure Data

Analysis Population Description

The Intent-to-treat analysis set in the Phase 2 part of the study included all participants with treatment group who were randomized to study treatment.

Arm/Group Title	Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)	Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)
Arm/Group Description:	Participants randomized to receive Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants randomized to receive 500 milligram per square meter (mg/m^2) of Pemetrexed as intravenous infusion over 10 minutes in combination with Cisplatin (75 mg/m^2 as an intravenous infusion over 2 hours) or Carboplatin (intravenously at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator) on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment or up to 6 cycles if or 4 cycles followed by Pemetrexed maintenance monotherapy.
Overall Number of Participants Analyzed	31	24
Median (90% Confidence Interval); Unit of Measure: Months
	10.15; (4.24 to 19.32)	4.34; (4.11 to 6.97)

35. Secondary Outcome

Title	Phase 2: (Randomized Part Only): Overall Survival (OS) Time
Description	Overall survival time was measured as time in months between the date of randomization and the date of death.
Time Frame	Up to 328 weeks

Outcome Measure Data

Analysis Population Description

The Intent-to-treat analysis set in the Phase 2 part of the study included all participants with treatment group who were randomized to study treatment.

Arm/Group Title	Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)	Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)
Arm/Group Description:	Participants randomized to receive Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants randomized to receive 500 milligram per square meter (mg/m^2) of Pemetrexed as intravenous infusion over 10 minutes in combination with Cisplatin (75 mg/m^2 as an intravenous infusion over 2 hours) or Carboplatin (intravenously at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator) on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment or up to 6 cycles if or 4 cycles followed by Pemetrexed maintenance monotherapy.
Overall Number of Participants Analyzed	31	24
Median (90% Confidence Interval); Unit of Measure: Months
	17.25; (12.12 to 29.14)	19.48; (15.90 to 21.82)

36. Secondary Outcome

Title	Phase 2 (Randomized Part Only): Percentage of Participants With Objective Response Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria
Description	Objective response (OR) was defined as the percentage of participants who had achieved complete response (CR) or partial response (PR) as the best overall response according to local radiological assessments from randomization/the first administration of the study treatment to the first observation of disease progression (PD). CR: defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame	Up to 328 weeks

Outcome Measure Data

Analysis Population Description

The Intent-to-treat analysis set in the Phase 2 part of the study included all participants with treatment group who were randomized to study treatment.

Arm/Group Title	Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)	Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)
Arm/Group Description:	Participants randomized to receive Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants randomized to receive 500 milligram per square meter (mg/m^2) of Pemetrexed as intravenous infusion over 10 minutes in combination with Cisplatin (75 mg/m^2 as an intravenous infusion over 2 hours) or Carboplatin (intravenously at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator) on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment or up to 6 cycles if or 4 cycles followed by Pemetrexed maintenance monotherapy.
Overall Number of Participants Analyzed	31	24
Measure Type: Number; Number (90% Confidence Interval); Unit of Measure: Percentage of Participants
	45.2; (29.7 to 61.3)	33.3; (17.8 to 52.1)

37. Secondary Outcome

Title	Phase 2 (Randomized Part Only): Percentage of Participants With Disease Control Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria
Description	Disease control defined as CR, PR, or stable disease(SD) as the best overall response according to local radiological assessments from the date of randomization/the first administration of the study treatment to the first observation of PD. CR:disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR:at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD:an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5mm. SD:as any cases that do not qualify for either PR/PD at minimum interval of 42 days after randomization/start of study treatment.
Time Frame	Up to 328 weeks

Outcome Measure Data

Analysis Population Description

The Intent-to-treat analysis set in the Phase 2 part of the study included all participants with treatment group who were randomized to study treatment.

Arm/Group Title	Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)	Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)
Arm/Group Description:	Participants randomized to receive Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants randomized to receive 500 milligram per square meter (mg/m^2) of Pemetrexed as intravenous infusion over 10 minutes in combination with Cisplatin (75 mg/m^2 as an intravenous infusion over 2 hours) or Carboplatin (intravenously at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator) on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment or up to 6 cycles if or 4 cycles followed by Pemetrexed maintenance monotherapy.
Overall Number of Participants Analyzed	31	24
Measure Type: Number; Number (90% Confidence Interval); Unit of Measure: Percentage of Participants
	83.9; (69.0 to 93.4)	70.8; (52.1 to 85.4)

38. Secondary Outcome

Title	Phase 2 (Non-Randomized Part Only): Progression-free Survival (PFS) Based on Tumor Assessment by Investigator
Description	Progression-free survival (assessed by Investigator) time was defined as the time in months from randomization to either first observation of radiologically confirmed progression disease by the Investigator or occurrence of death due to any cause within 84 days of either randomization or the last tumor assessment. PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm. PFS was measured using Kaplan-Meier (KM) estimates.
Time Frame	Up to 328 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 2: Single-arm Cohort (MET+ T790M Positive)
Arm/Group Description:	Participants with MET+ T790M positive Non-small Cell Lung Cancer (NSCLC) received a Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	15
Median (90% Confidence Interval); Unit of Measure: Months
	1.41; (1.35 to 4.90)

39. Secondary Outcome

Title	Phase 2 (Non-Randomized Part Only): Progression-free Survival (PFS) Based on Tumor Assessment by Independent Review Committee (IRC)
Description	Progression-free survival (assessed by Independent Review Committee) time was defined as the time in months from randomization to either first observation of radiologically confirmed progression disease by the IRC or occurrence of death due to any cause within 84 days of either randomization or the last tumor assessment. PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm. PFS was measured using Kaplan-Meier (KM) estimates.
Time Frame	Up to 328 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 2: Single-arm Cohort (MET+ T790M Positive)
Arm/Group Description:	Participants with MET+ T790M positive Non-small Cell Lung Cancer (NSCLC) received a Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	15
Median (90% Confidence Interval); Unit of Measure: Months
	2.63; (1.38 to 2.73)

40. Secondary Outcome

Title	Phase 2: (Non-Randomized Part Only): Overall Survival (OS) Time
Description	Overall survival time was measured as time in months between the date of randomization and the date of death.
Time Frame	Up to 328 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 2: Single-arm Cohort (MET+ T790M Positive)
Arm/Group Description:	Participants with MET+ T790M positive Non-small Cell Lung Cancer (NSCLC) received a Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	15
Median (90% Confidence Interval); Unit of Measure: Months
	25.86; (13.08 to 39.66)

41. Secondary Outcome

Title	Phase 2 (Non-Randomized Part Only): Percentage of Participants With Objective Response Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria
Description	Objective response (OR) was defined as the percentage of participants who had achieved complete response (CR) or partial response (PR) as the best overall response according to local radiological assessments from randomization/the first administration of the study treatment to the first observation of disease progression (PD). CR: defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame	Up to 328 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 2: Single-arm Cohort (MET+ T790M Positive)
Arm/Group Description:	Participants with MET+ T790M positive Non-small Cell Lung Cancer (NSCLC) received a Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	15
Measure Type: Number; Number (90% Confidence Interval); Unit of Measure: Percentage of Participants
	0; (0.0 to 18.1)

42. Secondary Outcome

Title	Phase 2 (Non-Randomized Part Only): Percentage of Participants With Disease Control Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria
Description	Disease control defined as CR, PR, or stable disease(SD) as the best overall response according to local radiological assessments from the date of randomization/the first administration of the study treatment to the first observation of PD. CR:disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR:at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD:an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5mm. SD:as any cases that do not qualify for either PR/PD at minimum interval of 42 days after randomization/start of study treatment.
Time Frame	Up to 328 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who had received any dose of the study medication.

Arm/Group Title	Phase 2: Single-arm Cohort (MET+ T790M Positive)
Arm/Group Description:	Participants with MET+ T790M positive Non-small Cell Lung Cancer (NSCLC) received a Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	15
Measure Type: Number; Number (90% Confidence Interval); Unit of Measure: Percentage of Participants
	40; (19.1 to 64.0)

43. Secondary Outcome

Title	Phase 2: Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status Scale Score at End of Treatment (EOT)
Description	EORTC QLQ-C30 is 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, dyspnoea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact. The EORTC QLQ-C30 GHS/QoL score ranges from 0 to 100; High score indicates better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL.
Time Frame	Baseline and EOT (up to 110 weeks)

Outcome Measure Data

Analysis Population Description

Quality of life (Qol) evaluable population set included ITT participants in the treatment group in which they actually received the treatment with a baseline and at least 1 evaluable on-treatment QoL questionnaire. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)	Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)	Phase 2: Single-arm Cohort (MET+ T790M Positive)
Arm/Group Description:	Participants randomized to receive Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants randomized to receive 500 milligram per square meter (mg/m^2) of Pemetrexed as intravenous infusion over 10 minutes in combination with Cisplatin (75 mg/m^2 as an intravenous infusion over 2 hours) or Carboplatin (intravenously at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator) on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment or up to 6 cycles if or 4 cycles followed by Pemetrexed maintenance monotherapy.	Participants with MET+ T790M positive Non-small Cell Lung Cancer (NSCLC) received a Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	22	21	10
Mean (Standard Deviation); Unit of Measure: Units on a Scale
	-16.29 (30.691)	-2.78 (22.869)	-24.19 (24.673)

44. Secondary Outcome

Title	Phase 2: Time-to-Symptom Progression (TTSP)
Description	TTSP was measured from randomization to symptomatic progression by lung cancer symptom scale (LCSS) used to measure symptom changes relevant to quality of life (QoL).It consisted of 9 items focused on cancer symptoms (loss of appetite, fatigue, cough, shortness of breath, blood in sputum, pain, symptoms of cancer, illness affecting normal activity, QoL).For each symptom score distance from left boundary to point where participant has marked line was measured in millimeters (mm).Total scale length was 100 mm. Symptomatic progression was defined as increase/worsening of average symptomatic burden index (ASBI) (mean of 6 major lung cancer specific symptom scores);Worsening defined as 10% increase of scale breadth from baseline. Score 0 indicate no/minimum symptoms;100 indicates maximum level of symptoms.
Time Frame	Up to 328 weeks

Outcome Measure Data

Analysis Population Description

Quality of life (Qol) evaluable population set included ITT participants in the treatment group in which they actually received the treatment with a baseline and at least 1 evaluable on-treatment QoL questionnaire.

Arm/Group Title	Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)	Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)	Phase 2: Single-arm Cohort (MET+ T790M Positive)
Arm/Group Description:	Participants randomized to receive Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants randomized to receive 500 milligram per square meter (mg/m^2) of Pemetrexed as intravenous infusion over 10 minutes in combination with Cisplatin (75 mg/m^2 as an intravenous infusion over 2 hours) or Carboplatin (intravenously at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator) on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment or up to 6 cycles if or 4 cycles followed by Pemetrexed maintenance monotherapy.	Participants with MET+ T790M positive Non-small Cell Lung Cancer (NSCLC) received a Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Overall Number of Participants Analyzed	29	22	15
Median (90% Confidence Interval); Unit of Measure: Months
	5.75; (1.41 to 11.86)	7.95; (2.07 to 17.05)	2.63; (1.41 to 8.31)

Adverse Events

Time Frame	Baseline up to 328 weeks
Adverse Event Reporting Description	The safety analysis set included all participants who had received any dose of the study medication.
Arm/Group Title	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg	Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)	Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)	Phase 2: Single-arm Cohort (MET+ T790M Positive)
Arm/Group Description	Participants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants randomized to receive Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment.	Participants randomized to receive 500 milligram per square meter (mg/m^2) of Pemetrexed as intravenous infusion over 10 minutes in combination with Cisplatin (75 mg/m^2 as an intravenous infusion over 2 hours) or Carboplatin (intravenously at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator) on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment or up to 6 cycles if or 4 cycles followed by Pemetrexed maintenance monotherapy.	Participants with MET+ T790M positive Non-small Cell Lung Cancer (NSCLC) received a Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
All-Cause Mortality
	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg	Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)	Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)	Phase 2: Single-arm Cohort (MET+ T790M Positive)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/6 (16.67%)	3/12 (25.00%)	23/31 (74.19%)	20/23 (86.96%)	10/15 (66.67%)
Serious Adverse Events
	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg	Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)	Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)	Phase 2: Single-arm Cohort (MET+ T790M Positive)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	4/6 (66.67%)	7/12 (58.33%)	13/31 (41.94%)	8/23 (34.78%)	5/15 (33.33%)
Blood and lymphatic system disorders
Anaemia * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	2/23 (8.70%)	0/15 (0.00%)
Cardiac disorders
Arrhythmia supraventricular * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Gastrointestinal disorders
Abdominal distension * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Abdominal pain * 1	0/6 (0.00%)	1/12 (8.33%)	1/31 (3.23%)	0/23 (0.00%)	0/15 (0.00%)
Constipation * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Vomiting * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	1/23 (4.35%)	0/15 (0.00%)
Ascites * 1	0/6 (0.00%)	0/12 (0.00%)	1/31 (3.23%)	0/23 (0.00%)	0/15 (0.00%)
Nausea * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	1/23 (4.35%)	0/15 (0.00%)
General disorders
Chest discomfort * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	1/23 (4.35%)	0/15 (0.00%)
Disease progression * 1	0/6 (0.00%)	1/12 (8.33%)	2/31 (6.45%)	1/23 (4.35%)	1/15 (6.67%)
Fatigue * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Non-cardiac chest pain * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Chest Pain * 1	0/6 (0.00%)	0/12 (0.00%)	1/31 (3.23%)	0/23 (0.00%)	0/15 (0.00%)
Face Oedema * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	1/23 (4.35%)	0/15 (0.00%)
Malaise * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	1/23 (4.35%)	0/15 (0.00%)
Oedema peripheral * 1	0/6 (0.00%)	0/12 (0.00%)	2/31 (6.45%)	0/23 (0.00%)	0/15 (0.00%)
Infections and infestations
Cellulitis * 1	1/6 (16.67%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Pneumonia * 1	1/6 (16.67%)	0/12 (0.00%)	0/31 (0.00%)	1/23 (4.35%)	1/15 (6.67%)
Atypical pneumonia * 1	0/6 (0.00%)	0/12 (0.00%)	1/31 (3.23%)	0/23 (0.00%)	0/15 (0.00%)
Herpes virus infection * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	1/23 (4.35%)	0/15 (0.00%)
Lower respiratory tract infection * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	1/23 (4.35%)	0/15 (0.00%)
Investigations
Amylase increased * 1	0/6 (0.00%)	0/12 (0.00%)	1/31 (3.23%)	1/23 (4.35%)	0/15 (0.00%)
Lipase increased * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	1/23 (4.35%)	0/15 (0.00%)
Neutrophil count decreased * 1	0/6 (0.00%)	0/12 (0.00%)	1/31 (3.23%)	2/23 (8.70%)	0/15 (0.00%)
White blood cell count decreased * 1	0/6 (0.00%)	0/12 (0.00%)	1/31 (3.23%)	1/23 (4.35%)	0/15 (0.00%)
Metabolism and nutrition disorders
Hyperglycaemia * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Decreased appetite * 1	0/6 (0.00%)	0/12 (0.00%)	1/31 (3.23%)	1/23 (4.35%)	0/15 (0.00%)
Hypoalbuminaemia * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	1/15 (6.67%)
Hypophosphataemia * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	1/23 (4.35%)	0/15 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	1/6 (16.67%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Back pain * 1	1/6 (16.67%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Myalgia * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system * 1	0/6 (0.00%)	1/12 (8.33%)	1/31 (3.23%)	0/23 (0.00%)	1/15 (6.67%)
Tumour pain * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	1/15 (6.67%)
Reproductive system and breast disorders
Benign prostatic hyperplasia * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea * 1	1/6 (16.67%)	0/12 (0.00%)	0/31 (0.00%)	1/23 (4.35%)	0/15 (0.00%)
Dyspnoea exertional * 1	0/6 (0.00%)	2/12 (16.67%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Dyspnoea paroxysmal nocturnal * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Haemoptysis * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Pleural effusion * 1	0/6 (0.00%)	1/12 (8.33%)	3/31 (9.68%)	1/23 (4.35%)	1/15 (6.67%)
Dyspnoea at rest * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	1/23 (4.35%)	0/15 (0.00%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform * 1	0/6 (0.00%)	0/12 (0.00%)	1/31 (3.23%)	0/23 (0.00%)	0/15 (0.00%)
1 Term from vocabulary, MedDRA V 20.0/24.0; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg	Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg	Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)	Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)	Phase 2: Single-arm Cohort (MET+ T790M Positive)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	6/6 (100.00%)	12/12 (100.00%)	31/31 (100.00%)	23/23 (100.00%)	13/15 (86.67%)
Blood and lymphatic system disorders
Anaemia * 1	0/6 (0.00%)	0/12 (0.00%)	5/31 (16.13%)	16/23 (69.57%)	4/15 (26.67%)
Leukopenia * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	1/23 (4.35%)	1/15 (6.67%)
Neutropenia * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	7/23 (30.43%)	1/15 (6.67%)
Thrombocytopenia * 1	0/6 (0.00%)	0/12 (0.00%)	1/31 (3.23%)	1/23 (4.35%)	1/15 (6.67%)
Cardiac disorders
Supraventricular extrasystoles * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	1/15 (6.67%)
Atrial fibrillation * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Cardiac discomfort * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Pericardial effusion * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Ear and labyrinth disorders
Tinnitus * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	2/23 (8.70%)	0/15 (0.00%)
Hypoacusis * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Endocrine disorders
Inappropriate antidiuretic hormone secretion * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Eye disorders
Eyelids pruritus * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	1/15 (6.67%)
Keratitis * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Gastrointestinal disorders
Abdominal distension * 1	0/6 (0.00%)	0/12 (0.00%)	4/31 (12.90%)	2/23 (8.70%)	0/15 (0.00%)
Abdominal pain * 1	1/6 (16.67%)	3/12 (25.00%)	1/31 (3.23%)	2/23 (8.70%)	0/15 (0.00%)
Abdominal pain upper * 1	0/6 (0.00%)	2/12 (16.67%)	3/31 (9.68%)	1/23 (4.35%)	0/15 (0.00%)
Cheilitis * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	1/15 (6.67%)
Constipation * 1	0/6 (0.00%)	3/12 (25.00%)	6/31 (19.35%)	6/23 (26.09%)	3/15 (20.00%)
Diarrhoea * 1	4/6 (66.67%)	10/12 (83.33%)	18/31 (58.06%)	4/23 (17.39%)	7/15 (46.67%)
Dyspepsia * 1	1/6 (16.67%)	2/12 (16.67%)	2/31 (6.45%)	0/23 (0.00%)	1/15 (6.67%)
Epigastric discomfort * 1	0/6 (0.00%)	0/12 (0.00%)	4/31 (12.90%)	1/23 (4.35%)	0/15 (0.00%)
Nausea * 1	2/6 (33.33%)	2/12 (16.67%)	7/31 (22.58%)	14/23 (60.87%)	2/15 (13.33%)
Stomatitis * 1	0/6 (0.00%)	1/12 (8.33%)	2/31 (6.45%)	0/23 (0.00%)	0/15 (0.00%)
Vomiting * 1	2/6 (33.33%)	3/12 (25.00%)	9/31 (29.03%)	11/23 (47.83%)	3/15 (20.00%)
Abdominal discomfort * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Gingival bleeding * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Haemorrhoidal haemorrhage * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
General disorders
Asthenia * 1	1/6 (16.67%)	0/12 (0.00%)	5/31 (16.13%)	5/23 (21.74%)	2/15 (13.33%)
Axillary pain * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	1/15 (6.67%)
Chest discomfort * 1	0/6 (0.00%)	1/12 (8.33%)	2/31 (6.45%)	0/23 (0.00%)	1/15 (6.67%)
Chest pain * 1	0/6 (0.00%)	0/12 (0.00%)	6/31 (19.35%)	1/23 (4.35%)	1/15 (6.67%)
Fatigue * 1	1/6 (16.67%)	5/12 (41.67%)	2/31 (6.45%)	3/23 (13.04%)	0/15 (0.00%)
Malaise * 1	0/6 (0.00%)	1/12 (8.33%)	1/31 (3.23%)	2/23 (8.70%)	1/15 (6.67%)
Oedema * 1	0/6 (0.00%)	1/12 (8.33%)	4/31 (12.90%)	0/23 (0.00%)	1/15 (6.67%)
Oedema peripheral * 1	2/6 (33.33%)	3/12 (25.00%)	12/31 (38.71%)	1/23 (4.35%)	0/15 (0.00%)
Pyrexia * 1	1/6 (16.67%)	2/12 (16.67%)	4/31 (12.90%)	1/23 (4.35%)	2/15 (13.33%)
Local swelling * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Non-cardiac chest pain * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Pain * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Peripheral swelling * 1	1/6 (16.67%)	0/12 (0.00%)	2/31 (6.45%)	0/23 (0.00%)	0/15 (0.00%)
Hepatobiliary disorders
Hepatic function abnormal * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	1/23 (4.35%)	1/15 (6.67%)
Liver injury * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	1/15 (6.67%)
Infections and infestations
Conjunctivitis * 1	0/6 (0.00%)	0/12 (0.00%)	3/31 (9.68%)	0/23 (0.00%)	1/15 (6.67%)
Gingivitis * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	1/15 (6.67%)
Influenza * 1	0/6 (0.00%)	0/12 (0.00%)	1/31 (3.23%)	0/23 (0.00%)	1/15 (6.67%)
Localised infection * 1	0/6 (0.00%)	0/12 (0.00%)	1/31 (3.23%)	0/23 (0.00%)	1/15 (6.67%)
Nasopharyngitis * 1	0/6 (0.00%)	0/12 (0.00%)	3/31 (9.68%)	1/23 (4.35%)	0/15 (0.00%)
Oral herpes * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	1/15 (6.67%)
Paronychia * 1	0/6 (0.00%)	0/12 (0.00%)	7/31 (22.58%)	0/23 (0.00%)	1/15 (6.67%)
Pneumonia * 1	0/6 (0.00%)	0/12 (0.00%)	2/31 (6.45%)	0/23 (0.00%)	3/15 (20.00%)
Upper respiratory tract infection * 1	0/6 (0.00%)	0/12 (0.00%)	4/31 (12.90%)	0/23 (0.00%)	1/15 (6.67%)
Urinary tract infection * 1	0/6 (0.00%)	0/12 (0.00%)	4/31 (12.90%)	0/23 (0.00%)	1/15 (6.67%)
Cellulitis * 1	1/6 (16.67%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Folliculitis * 1	1/6 (16.67%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Influenza * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Paronychia * 1	2/6 (33.33%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Pneumonia * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Investigations
Activated partial thromboplastin time prolonged * 1	0/6 (0.00%)	0/12 (0.00%)	3/31 (9.68%)	2/23 (8.70%)	0/15 (0.00%)
Alanine aminotransferase increased * 1	1/6 (16.67%)	0/12 (0.00%)	10/31 (32.26%)	2/23 (8.70%)	1/15 (6.67%)
Amylase increased * 1	4/6 (66.67%)	2/12 (16.67%)	11/31 (35.48%)	4/23 (17.39%)	4/15 (26.67%)
Aspartate aminotransferase increased * 1	1/6 (16.67%)	0/12 (0.00%)	5/31 (16.13%)	3/23 (13.04%)	2/15 (13.33%)
Blood albumin decreased * 1	0/6 (0.00%)	0/12 (0.00%)	3/31 (9.68%)	1/23 (4.35%)	3/15 (20.00%)
Blood alkaline phosphatase increased * 1	3/6 (50.00%)	0/12 (0.00%)	2/31 (6.45%)	5/23 (21.74%)	2/15 (13.33%)
Blood creatinine increased * 1	2/6 (33.33%)	0/12 (0.00%)	4/31 (12.90%)	6/23 (26.09%)	2/15 (13.33%)
Blood urea increased * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	3/23 (13.04%)	0/15 (0.00%)
C-reactive protein increased * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	1/15 (6.67%)
Creatinine renal clearance decreased * 1	2/6 (33.33%)	0/12 (0.00%)	3/31 (9.68%)	3/23 (13.04%)	1/15 (6.67%)
Electrocardiogram QT prolonged * 1	3/6 (50.00%)	1/12 (8.33%)	3/31 (9.68%)	2/23 (8.70%)	1/15 (6.67%)
Gamma-glutamyltransferase increased * 1	1/6 (16.67%)	0/12 (0.00%)	1/31 (3.23%)	4/23 (17.39%)	1/15 (6.67%)
Haemoglobin decreased * 1	0/6 (0.00%)	0/12 (0.00%)	2/31 (6.45%)	1/23 (4.35%)	1/15 (6.67%)
International normalised ratio increased * 1	3/6 (50.00%)	0/12 (0.00%)	0/31 (0.00%)	1/23 (4.35%)	1/15 (6.67%)
Lipase increased * 1	2/6 (33.33%)	2/12 (16.67%)	8/31 (25.81%)	3/23 (13.04%)	2/15 (13.33%)
Neutrophil count decreased * 1	0/6 (0.00%)	1/12 (8.33%)	2/31 (6.45%)	9/23 (39.13%)	1/15 (6.67%)
Platelet count decreased * 1	1/6 (16.67%)	0/12 (0.00%)	2/31 (6.45%)	6/23 (26.09%)	0/15 (0.00%)
Prothrombin time prolonged * 1	3/6 (50.00%)	0/12 (0.00%)	1/31 (3.23%)	2/23 (8.70%)	1/15 (6.67%)
Weight decreased * 1	0/6 (0.00%)	3/12 (25.00%)	6/31 (19.35%)	6/23 (26.09%)	3/15 (20.00%)
White blood cell count decreased * 1	1/6 (16.67%)	0/12 (0.00%)	2/31 (6.45%)	12/23 (52.17%)	2/15 (13.33%)
Bacterial test positive * 1	1/6 (16.67%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Blood glucose increased * 1	1/6 (16.67%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Metabolism and nutrition disorders
Decreased appetite * 1	2/6 (33.33%)	4/12 (33.33%)	11/31 (35.48%)	10/23 (43.48%)	3/15 (20.00%)
Hyperglycaemia * 1	0/6 (0.00%)	2/12 (16.67%)	2/31 (6.45%)	4/23 (17.39%)	0/15 (0.00%)
Hyperkalaemia * 1	0/6 (0.00%)	0/12 (0.00%)	2/31 (6.45%)	2/23 (8.70%)	0/15 (0.00%)
Hypermagnesaemia * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	2/23 (8.70%)	0/15 (0.00%)
Hypoalbuminaemia * 1	2/6 (33.33%)	1/12 (8.33%)	9/31 (29.03%)	1/23 (4.35%)	2/15 (13.33%)
Hypocalcaemia * 1	2/6 (33.33%)	1/12 (8.33%)	6/31 (19.35%)	3/23 (13.04%)	2/15 (13.33%)
Hypochloraemia * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	2/23 (8.70%)	0/15 (0.00%)
Hypokalaemia * 1	0/6 (0.00%)	1/12 (8.33%)	3/31 (9.68%)	6/23 (26.09%)	2/15 (13.33%)
Hypomagnesaemia * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	2/23 (8.70%)	0/15 (0.00%)
Hyponatraemia * 1	1/6 (16.67%)	2/12 (16.67%)	2/31 (6.45%)	3/23 (13.04%)	0/15 (0.00%)
Hypoproteinaemia * 1	2/6 (33.33%)	0/12 (0.00%)	3/31 (9.68%)	5/23 (21.74%)	2/15 (13.33%)
Hypoglycaemia * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Hypophosphataemia * 1	1/6 (16.67%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Musculoskeletal and connective tissue disorders
Back pain * 1	1/6 (16.67%)	2/12 (16.67%)	4/31 (12.90%)	1/23 (4.35%)	1/15 (6.67%)
Bone pain * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	1/15 (6.67%)
Muscle twitching * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	1/15 (6.67%)
Musculoskeletal chest pain * 1	0/6 (0.00%)	2/12 (16.67%)	2/31 (6.45%)	0/23 (0.00%)	1/15 (6.67%)
Pain in extremity * 1	1/6 (16.67%)	1/12 (8.33%)	2/31 (6.45%)	0/23 (0.00%)	1/15 (6.67%)
Arthralgia * 1	1/6 (16.67%)	0/12 (0.00%)	3/31 (9.68%)	0/23 (0.00%)	0/15 (0.00%)
Myalgia * 1	1/6 (16.67%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Neck pain * 1	0/6 (0.00%)	0/12 (0.00%)	2/31 (6.45%)	0/23 (0.00%)	0/15 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	1/15 (6.67%)
Nervous system disorders
Dizziness * 1	0/6 (0.00%)	2/12 (16.67%)	3/31 (9.68%)	4/23 (17.39%)	0/15 (0.00%)
Headache * 1	0/6 (0.00%)	1/12 (8.33%)	7/31 (22.58%)	3/23 (13.04%)	0/15 (0.00%)
Cognitive disorder * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Dysgeusia * 1	1/6 (16.67%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Memory impairment * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Psychiatric disorders
Innsomnia * 1	1/6 (16.67%)	1/12 (8.33%)	5/31 (16.13%)	2/23 (8.70%)	0/15 (0.00%)
Renal and urinary disorders
Haematuria * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	1/23 (4.35%)	1/15 (6.67%)
Hydronephrosis * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Ureterolithiasis * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Reproductive system and breast disorders
Benign prostatic hyperplasia * 1	0/6 (0.00%)	2/12 (16.67%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Vulvovaginal dryness * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	3/6 (50.00%)	1/12 (8.33%)	8/31 (25.81%)	5/23 (21.74%)	3/15 (20.00%)
Dyspnoea * 1	0/6 (0.00%)	1/12 (8.33%)	8/31 (25.81%)	2/23 (8.70%)	3/15 (20.00%)
Haemoptysis * 1	1/6 (16.67%)	1/12 (8.33%)	4/31 (12.90%)	0/23 (0.00%)	3/15 (20.00%)
Pleural effusion * 1	0/6 (0.00%)	1/12 (8.33%)	2/31 (6.45%)	1/23 (4.35%)	1/15 (6.67%)
Productive cough * 1	1/6 (16.67%)	0/12 (0.00%)	3/31 (9.68%)	3/23 (13.04%)	0/15 (0.00%)
Rhinorrhoea * 1	0/6 (0.00%)	1/12 (8.33%)	2/31 (6.45%)	2/23 (8.70%)	0/15 (0.00%)
Dyspnoea exertional * 1	3/6 (50.00%)	5/12 (41.67%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Dyspnoea paroxysmal nocturnal * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Hiccups * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Pulmonary thrombosis * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform * 1	1/6 (16.67%)	0/12 (0.00%)	4/31 (12.90%)	0/23 (0.00%)	0/15 (0.00%)
Dry skin * 1	0/6 (0.00%)	4/12 (33.33%)	3/31 (9.68%)	0/23 (0.00%)	0/15 (0.00%)
Palmar-plantar erythrodysaesthesia syndrome * 1	0/6 (0.00%)	0/12 (0.00%)	2/31 (6.45%)	0/23 (0.00%)	0/15 (0.00%)
Pruritus * 1	2/6 (33.33%)	4/12 (33.33%)	4/31 (12.90%)	2/23 (8.70%)	2/15 (13.33%)
Rash * 1	3/6 (50.00%)	5/12 (41.67%)	8/31 (25.81%)	0/23 (0.00%)	4/15 (26.67%)
Seborrhoeic dermatitis * 1	0/6 (0.00%)	0/12 (0.00%)	2/31 (6.45%)	0/23 (0.00%)	0/15 (0.00%)
Skin fissures * 1	0/6 (0.00%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	1/15 (6.67%)
Skin hyperpigmentation * 1	0/6 (0.00%)	0/12 (0.00%)	2/31 (6.45%)	0/23 (0.00%)	0/15 (0.00%)
Acne * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Erythema * 1	1/6 (16.67%)	0/12 (0.00%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Intertrigo * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
Social circumstances
Inadequate diet * 1	0/6 (0.00%)	0/12 (0.00%)	1/31 (3.23%)	2/23 (8.70%)	0/15 (0.00%)
Vascular disorders
Peripheral embolism * 1	0/6 (0.00%)	1/12 (8.33%)	0/31 (0.00%)	0/23 (0.00%)	0/15 (0.00%)
1 Term from vocabulary, MedDRA V 20.0/24.0; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

 

Results Point of Contact

• Name/Title: Communication Center
• Organization: Merck KGaA, Darmstadt, Germany
• Phone: +49-6151-72-5200
• EMail: service@emdgroup.com

Publications of Results:

Wu YL, Cheng Y, Zhou J, Lu S, Zhang Y, Zhao J, Kim DW, Soo RA, Kim SW, Pan H, Chen YM, Chian CF, Liu X, Tan DSW, Bruns R, Straub J, Johne A, Scheele J, Park K, Yang JC; INSIGHT Investigators. Tepotinib plus gefitinib in patients with EGFR-mutant non-small-cell lung cancer with MET overexpression or MET amplification and acquired resistance to previous EGFR inhibitor (INSIGHT study): an open-label, phase 1b/2, multicentre, randomised trial. Lancet Respir Med. 2020 Nov;8(11):1132-1143. doi: 10.1016/S2213-2600(20)30154-5. Epub 2020 May 29. Erratum In: Lancet Respir Med. 2020 Jul;8(7):e59.

• Responsible Party: Merck KGaA, Darmstadt, Germany
• ClinicalTrials.gov Identifier: NCT01982955
• Other Study ID Numbers: EMR 200095-006; 2016-001604-28 ( EudraCT Number )
• First Submitted: October 29, 2013
• First Posted: November 13, 2013
• Results First Submitted: July 7, 2020
• Results First Posted: July 23, 2020
• Last Update Posted: November 8, 2022