A DLT was defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, progressive disease, inter-current illness, or concomitant medications, that despite optimal therapeutic intervention that occurred within the first 21 days of treatment with capmatinib in combination with osimertinib.

FAS included all participants who received any component of the study treatment.

PFS was defined as time from date of randomization to the date of first documented disease progression (PD) based on Blinded Independent Review Committee (BIRC) as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), or death from any cause, whichever occurred first. Progression was defined as a ≥20% increase in sum of longest diameters (SLD) compared to smallest SLD in the study, or progression of non-target lesions or new lesions.

Due to early study termination, the randomized part of the study was not initiated. Hence the data was not collected for the outcome measures in the randomized part of the study.

Number of participants with at least one dose interruption and dose reduction were reported for each study drug.

Safety set included all participants who received at least one dose of study treatment.

Dose intensity was computed as the ratio of actual cumulative dose (milligrams) received and actual duration of exposure (weeks) to study drug.

Safety set included all participants who received at least one dose of study treatment.

Duration of exposure is defined as the time (in weeks) between the first and the last dose of study treatment.

Safety set included all participants who received at least one dose of study treatment.

Blood samples were collected. Cmax of capmatinib was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

Actual recorded sampling times were considered for the calculations

PK analysis set included all participants who provided at least one evaluable PK concentration. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.

Blood samples were collected. Cmax of osimertinib and its metabolites (AZ5104 and AZ7550) was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

PK analysis set included all participants who provided at least one evaluable PK concentration. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available at specified timepoint.

Blood samples were collected. Tmax of capmatinib was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

Actual recorded sampling times were considered for the calculations

PK analysis set included all participants who provided at least one evaluable PK concentration. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.

Blood samples were collected. Tmax of osimertinib and its metabolites (AZ5104 and AZ7550) was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

Actual recorded sampling times were considered for the calculations

PK analysis set included all participants who provided at least one evaluable PK concentration. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available at specified timepoint.

Blood samples were collected. AUClast of capmatinib was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

PK analysis set included all participants who provided at least one evaluable PK concentration. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.

Blood samples were collected. AUClast of osimertinib and its metabolites (AZ5104 and AZ7550) was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

PK analysis set included all participants who provided at least one evaluable PK concentration. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available at specified timepoint.

ORR was defined as the percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR), as per investigator judgment and according to RECIST v1.1. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: ≥30% decrease in the SLD of the target lesions or no new lesions or no progression of non-target lesions.

FAS included all participants who received any component of the study treatment.

DOR was defined as the time from first documented response of CR or PR to the date of first documented PD or death due to any cause. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: ≥30% decrease in the SLD of the target lesions or no new lesions or no progression of non-target lesions; PD: ≥20% increase in SLD compared to the smallest SLD in the study, or progression of non-target lesions or new lesions.

FAS included all participants who received any component of the study treatment. 'Overall number of participants analyzed' indicates the number of participants with CR or PR.

TTR was defined as the duration of time between the date of fist dose of treatmwnr and the date of the first documented response of either CR or PR as per investigator judgment and according to RECIST v1.1 criteria. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: ≥30% decrease in SLD of the target lesions or no new lesions or no progression of non-target lesions.

FAS included all participants who received any component of the study treatment. 'Overall number of participants analyzed' indicates the number of participants with CR or PR.

DCR was defined as the percentage of participants with a BOR of CR, PR, and stable disease (SD) as per investigator judgment and according to RECIST v1.1. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: ≥30% decrease in SLD of the target lesions or no new lesions or no progression of non-target lesions; SD: Neither sufficient shrinkage to qualify for PR or CR nor and increase in lesions which would qualify for PD. PD: ≥20% increase in SLD compared to the smallest SLD in the study, or progression of non-target lesions or new lesions.

FAS included all participants who received any component of the study treatment.

PFS was defined as the time (in months) from first dose of treatment to the date of the first documented progression or death due to any cause as per investigator judgment and according to RECIST v1.1. Progression was defined as a ≥20% increase in SLD compared to smallest SLD in the study, or progression of non-target lesions or new lesions. PFS was censored if no PFS event (progression or death) was observed.

FAS included all participants who received any component of the study treatment.

ORR was defined as the percentage of participants with confirmed BOR of CR or PR, as per BIRC by RECIST v1.1. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: ≥30% decrease in SLD of the target lesions or no new lesions or no progression of non-target lesions.

Due to early study termination, the randomized part of the study was not conducted. Hence the data was not collected for the outcome measures in the randomized part of the study.

OIRR was defined as the percentage of participants with a confirmed best overall intracranial response (BOIR) of CR or PR as per BIRC according to Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. Criteria for CR: Disappearance of all CNS target and non-target lesions sustained for at least 4 weeks, with no new lesions, and no use of corticosteroids. PR: ≥30% decrease in the SLD of CNS target lesions or no new lesions or and stable to decreased corticosteroid dose.

Due to early study termination, the randomized part of the study was not conducted. Hence the data was not collected for the outcome measures in the randomized part of the study.

DOR was defined as the time from the first documented response of CR or PR to the date of first documented progression or death as per BIRC according to RECIST v1.1 criteria. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: ≥30% decrease in SLD of the target lesions or no new lesions or no progression of non-target lesions; PD: ≥20% increase in SLD compared to the smallest SLD in the study, or progression of non-target lesions or new lesions.

Due to early study termination, the randomized part of the study was not conducted. Hence the data was not collected for the outcome measures in the randomized part of the study.

TTR was defined as duration of time between the date of randomization and the date of first documented response of either CR or PR as per BIRC according to RECIST v1.1 criteria. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: ≥30% decrease in SLD of the target lesions or no new lesions or no progression of non-target lesions.

Due to early study termination, the randomized part of the study was not conducted. Hence the data was not collected for the outcome measures in the randomized part of the study.

DCR was defined as the percentage of participants with CR or PR or SD as per BIRC according to RECIST v1.1 criteria. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: ≥30% decrease in SLD of the target lesions or no new lesions or no progression of non-target lesions; SD: Neither sufficient shrinkage to qualify for PR or CR nor and increase in lesions which would qualify for PD. PD: ≥20% increase in SLD compared to the smallest SLD in the study, or progression of non-target lesions or new lesions.

Due to early study termination, the randomized part of the study was not conducted. Hence the data was not collected for the outcome measures in the randomized part of the study.

PFS2 was defined as the time from date of randomization to the first documented progression on the next line therapy as per investigator judgment according to RECIST v1.1 response criteria or death due to any cause.

Due to early study termination, the randomized part of the study was not conducted. Hence the data was not collected for the outcome measures in the randomized part of the study.

Cmax of capmatinib calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

Due to early study termination, the randomized part of the study was not conducted. Hence the data was not collected for the outcome measures in the randomized part of the study.

Cmax of osimertinib and its metabolites (AZ5104 and AZ7550) calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

Due to early study termination, the randomized part of the study was not conducted. Hence the data was not collected for the outcome measures in the randomized part of the study.

OS was defined as the time from date of randomization to date of death due to any cause.

Due to early study termination, the randomized part of the study was not conducted. Hence the data was not collected for the outcome measures in the randomized part of the study.

EORTC QLQ-C30 is a questionnaire developed to assess the quality of life of cancer patients. It contains 30 items and is composed of both multi-item scales and single-item measures based on the participant's experience over the past week. These include five scales (physical, role, emotional, cognitive, and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial impact) and a global health status/quality of life scale (QoL) scale. All of the scales and single-item measures range in score from 0 to 100. A high score for a functional scale represents a high /healthy level of functioning; a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology/problems.

Due to early study termination, the randomized part of the study was not conducted. Hence the data was not collected for the outcome measures in the randomized part of the study.

EORTC QLQ-LC13 is used in conjunction with the EORTC QLQ-C30 and provides information on an additional 13 items specifically related to lung cancer. The five domains of the LC13 include pain, dyspnea, coughing and hemoptysis, and are based on their presence over the past week. All but the pain domain are scored on a 4 point Likert scale ranging from "not at all" to "very much". Pain score is based on its presence, hence yes or no. Scores are averaged and transformed to 0 to 100. A higher score indicates a higher presence of symptoms.

Due to early study termination, the randomized part of the study was not conducted. Hence the data was not collected for the outcome measures in the randomized part of the study.

EQ-5D-5L is a standardized measure of health status developed by the EuroQol (EQ) Group in order to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of 2 pages - the descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of these dimensions, the participant self-assigned a score: from 1 (no problems) to 5 (extreme problems). The questionnaire also includes a Visual Analogue Scale (VAS), where the participant is asked to rate current health status on a scale of 0 to 100, with 0 being the worst imaginable health state.

Due to early study termination, the randomized part of the study was not conducted. Hence the data was not collected for the outcome measures in the randomized part of the study.

The NCCN FACT-Brain Symptom Index version 2.0 (FBrSI) is a questionnaire used to explore changes in symptoms associated with potential brain metastases (BM). The symptoms module contains 12 items with a recall period of the past 7 days. The participant responds to 12 statements and indicates to what extent it applies to them on a 5-point Likert response scale from "not at all"=0 to "very much"=4. Higher scores indicates a greater impact of symptoms on the participant's quality of life.

Due to early study termination, the randomized part of the study was not conducted. Hence the data was not collected for the outcome measures in the randomized part of the study.

Time to symptom deterioration from baseline from baseline for participant scores from the EORTC QLQ-C30 questionnaire. EORTC QLQ-C30 is a questionnaire developed to assess the quality of life of cancer patients. It contains 30 items and is composed of both multi-item scales and single-item measures based on the participant's experience over the past week. These include five scales (physical, role, emotional, cognitive, and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial impact) and a global health status/quality of life scale (QoL) scale. All of the scales and single-item measures range in score from 0 to 100. A high score for a functional scale represents a high /healthy level of functioning; a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology/problems.

Due to early study termination, the randomized part of the study was not conducted. Hence the data was not collected for the outcome measures in the randomized part of the study.

Time to symptom deterioration from baseline for participant scores from EORTC QLQ-LC13 questionnaire. EORTC QLQ-LC13 is used in conjunction with the EORTC QLQ-C30 and provides information on an additional 13 items specifically related to lung cancer. The five domains of the LC13 include pain, dyspnea, coughing and hemoptysis, and are based on their presence over the past week. All but the pain domain are scored on a 4 point Likert scale ranging from "not at all" to "very much". Pain score is based on its presence, hence yes or no. Scores are averaged and transformed to 0 to 100. A higher score indicates a higher presence of symptoms.

Due to early study termination, the randomized part of the study was not conducted. Hence the data was not collected for the outcome measures in the randomized part of the study.

Time to symptom deterioration from baseline for participant scores from the NCCN FBrSl questionnaire. The NCCN FACT-Brain Symptom Index version 2.0 (FBrSI) is a questionnaire used to explore changes in symptoms associated with potential brain metastases (BM). The symptoms module contains 12 items with a recall period of the past 7 days. The participant responds to 12 statements and indicates to what extent it applies to them on a 5-point Likert response scale from "not at all"=0 to "very much"=4. Higher scores indicates a greater impact of symptoms on the participant's quality of life.

Due to early study termination, the randomized part of the study was not conducted. Hence the data was not collected for the outcome measures in the randomized part of the study.

DOIR was defined as the time from the date of first documented intracranial response of either CR or PR to the date of the first documented intracranial progression per RANO-BM criteria as assessed by BIRC review or the date of death due to any cause. Criteria for CR: Disappearance of all CNS target and non-target lesions sustained for at least 4 weeks, with no new lesions, and no use of corticosteroids; PR: ≥30% decrease in the SLD of CNS target lesions or no new lesions, and stable to decreased corticosteroid dose.

Due to early study termination, the randomized part of the study was not conducted. Hence the data was not collected for the outcome measures in the randomized part of the study.

TTIR was defined as the time from the date of randomization to the date of the first documented intracranial response of either CR or PR as per BIRC according to RANO-BM criteria. Criteria for CR: Disappearance of all CNS target and non-target lesions sustained for at least 4 weeks, with no new lesions, and no use of corticosteroids; PR: ≥30% decrease in the SLD of CNS target lesions or no new lesions, and stable to decreased corticosteroid dose.

Due to early study termination, the randomized part of the study was not conducted. Hence the data was not collected for the outcome measures in the randomized part of the study.

IDCR was defined as the percentage of participants with a confirmed BOIR of CR or PR or SD as per BIRC according to RANO-BM criteria. Criteria for CR: Disappearance of all CNS target and non-target lesions sustained for at least 4 weeks, with no new lesions, and no use of corticosteroids; PR: ≥30% decrease in the SLD of CNS target lesions or no new lesions, and stable to decreased corticosteroid dose; SD: Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.

Due to early study termination, the randomized part of the study was not conducted. Hence the data was not collected for the outcome measures in the randomized part of the study.