Study Evaluating Efficacy and Safety of Capmatinib in Combination With Osimertinib in Adult Subjects With Non-small Cell Lung Cancers as Second Line Therapy

A Phase III Randomized, Controlled, Open-label, Multicenter, Global Study of Capmatinib in Combination With Osimertinib Versus Platinum - Pemetrexed Based Doublet Chemotherapy in Patients With Locally Advanced or Metastatic NSCLC Harboring EGFR Activating Mutations Who Have Progressed on Prior Generation EGFR-TKI Therapy and Whose Tumors Are T790M Mutation Negative and Harbor MET Amplification (GEOMETRY-E)

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04816214

Acronym

GEOMETRY-E

Enrollment

Registered

2021-03-25

Start date

2021-09-22

Completion date

2022-12-27

Last updated

2024-03-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

INC280, capmatinib, osimertinib, pemetrexed, platinum-based chemotherapy, NSCLC, Non-Small Cell Lung Cancer, Carcinoma, EGFR Mutation, T790M negative, MET amplification, second line therapy, GEOMETRY, GEOMETRY-E

Brief summary

This study aimed to evaluate the anticancer activity of capmatinib in combination with osimertinib compared to platinum-pemetrexed based doublet chemotherapy as second line treatment in patients with advanced or metastatic non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation, T790M negative, mesenchymal-to-epithelial transition factor (MET) amplified who progressed following EGFR tyrosine kinase inhibitors (TKIs).

Detailed description

This was a multicenter, open-label, randomized, active-controlled, global phase III study that enrolled adult participants with locally advanced or metastatic NSCLC with epidermal growth factor receptor (EGFR) activating mutation, T790M negative, mesenchymal-to-epithelial transition factor (MET) amplified who had progressed following EGFR tyrosine kinase inhibitors (TKIs). The study was conducted in two parts. The initial part was a safety run-in part, which aimed at assessing the safety and tolerability of capmatinib in combination with osimertinib and at determining the recommended dosage for the subsequent randomized part. The randomized part compared the efficacy and safety of capmatinib in combination with osimertinib to a platinum-based doublet chemotherapy regimen using either cisplatin or carboplatin, combined with pemetrexed, as second-line treatment.The randomized part was not initiated. In the randomized part (if initiated), participants were to receive their assigned treatment (either capmatinib in combination with osimertinib or platinum-pemetrexed based doublet chemotherapy) until they experienced any of the following: documented disease progression according to the Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1) as assessed by the investigator during the run-in part and confirmed by a blinded independent review committee (BIRC) during the randomized part, withdrawal of consent, pregnancy, lost to follow-up, or death. Participants who progressed in the platinum-pemetrexed arm were to be permitted to switch to capmatinib in combination with osimertinib therapy after BIRC-confirmed, RECIST 1.1-defined progressive disease. If, in the judgment of the investigator, there was evidence of clinical benefit and the participant wished to continue, study treatment could be continued beyond the initial disease progression according to RECIST 1.1 criteria. After treatment discontinuation, all participants were to be followed for safety evaluations during the safety follow-up period. On 11-May-2022, Novartis decided to halt enrollment for this study due to a business consideration unrelated to any safety concerns. Ongoing patients in the run-in part were allowed to continue treatment through other post-trial drug supply options, as applicable. On 27-Dec-2022 the last patient was transitioned off the study, and following the study protocol this date was declared the Global end of trial date. Randomized part was not initiated.

Interventions

DRUGCapmatinib

Capmatinib was available as a film-coated tablet for oral use, with a strength of either 150 mg or 200 mg. The initial dose of the combination therapy consisted of capmatinib 400 mg administered orally twice daily (b.i.d).

DRUGOsimertinib

Osimertinib was available as a tablet for oral use, with a strength of either 80 mg or 40 mg. The initial dose of the combination therapy consisted of osimertinib 80 mg administered orally once per day (q.d)

DRUGPemetrexed

Pemetrexed concentrate for solution for intravenous use was to be administered intravenously. The procurement of pemetrexed was to be done locally, following local practices and regulations.

DRUGCisplatin

Cisplatin concentrate for solution for intravenous use was to beadministered intravenously during the study. The procurement of cisplatin was to be done locally, following local practices and regulations.

DRUGCarboplatin

Carboplatin concentrate for solution for intravenous use was to be administered intravenously during the study. The procurement of carboplatin was to be done locally, following local practices and regulations.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

The study was terminated early based on Sponsor's decision unrelated to any safety concerns and the randomized part of the study was not initiated

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

Key Inclusion Criteria: * Histologically or cytologically confirmed diagnosis of NSCLC with EGFR mutations known to be associated with EGFR TKI sensitivity, EGFR T790M negative and MET gene amplification * Stage IIIB/IIIC or IV NSCLC * Participants must have progressed on one prior line of therapy (1st/2nd generation EGFR TKIs, osimertinib or other third generation EGFR TKIs) for advanced/metastatic disease (stage IIIB/IIIC and must be candidates for platinum (cisplatin or carboplatin) - pemetrexed doublet based chemotherapy * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 * Participants must have recovered from all toxicities related to prior systemic therapy to grade ≤ 1 Common Terminology Criteria Adverse Event 5.0 (CTCAE v 5.0) * At least one measurable lesion as defined by RECIST 1.1 * Participants must have adequate organ function Key

Exclusion criteria

* Prior treatment with any MET inhibitor or HGF-targeting therapy * Participants with symptomatic central nervous system (CNS) metastases who were neurologically unstable or had required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms * Carcinomatous meningitis * Presence or history of a malignant disease other than NSCLC that had been diagnosed and/or required therapy within the past 3 years * Presence or history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis * Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome * Clinically significant, uncontrolled heart diseases * known druggable molecular alterations that may render participants eligible for alternative targeted therapies

Design outcomes

Primary

Measure	Time frame	Description
Run-in Part: Number of Participants With Dose Limiting Toxicities (DLTs)	Up to 21 Days	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.
Randomized Part: Progression Free Survival (PFS) Based on BIRC Assessment	From randomization to first documented progression or deaths, planned to be assessed up to 37 months	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.

Secondary

Measure	Time frame	Description
Run-in Part: Area Under the Curve to the Last Measurable Concentration (AUClast) of Capmatinib	Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)	Blood samples were collected. AUClast of capmatinib was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Run-in Part: Area Under the Curve to the Last Measurable Concentration (AUClast) of Osimertinib and Its Metabolites (AZ5104 and AZ7550)	Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)	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.
Run-in Part: Number of Participants With at Least One Dose Interruption and Dose Reduction of Each Study Drug	From the first dose until last dose of study treatment, assessed up to 39 weeks	Number of participants with at least one dose interruption and dose reduction were reported for each study drug.
Run-in Part: Dose Intensity of Each Study Drug	From the first dose until last dose of study treatment, assessed up to 39 weeks	Dose intensity was computed as the ratio of actual cumulative dose (milligrams) received and actual duration of exposure (weeks) to study drug.
Run-in Part: Median Duration of Exposure to Each Study Drug	From the first dose until last dose of study treatment, assessed up to 39 weeks	Duration of exposure is defined as the time (in weeks) between the first and the last dose of study treatment.
Run-in Part: Maximum Plasma Concentration (Cmax) of Capmatinib	Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)	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
Run-in Part: Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolites (AZ5104 and AZ7550)	Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)	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.
Run-in Part: Time to Maximum Plasma Concentration (Tmax) of Capmatinib	Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)	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
Run-in Part: Time to Maximum Plasma Concentration (Tmax) of Osimertinib and Its Metabolites (AZ5104 and AZ7550)	Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)	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
Run-in Part: Overall Response Rate (ORR) as Per Investigator Assessment	Up to end of study, assessed up to 39 weeks	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.
Run-in Part: Duration of Response (DOR) as Per Investigator Assessment	Up to disease progression or death or end of study, assessed up to 39 weeks	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.
Run-in Part: Time to Response (TTR) as Per Investigator Assessment	From first dose of treatment up to end of study, assessed up to 39 weeks	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.
Run-in Part: Disease Control Rate (DCR) as Per Investigator Assessment	From randomization up to end of study, assessed up to 39 weeks	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.
Run-in Part: Progression-Free Survival (PFS) as Per Investigator Assessment	From first dose of treatment until first documented progression or death or end of study, assessed up to 39 weeks	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.
Randomized Part: Overall Response Rate (ORR) as Per BIRC Assessment	Planned to be assessed up to 37 months	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.
Randomized Part: Overall Intracranial Response Rate (OIRR) as Per BIRC Assessment	Planned to be assessed up to 37 months	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.
Randomized Part: Duration of Response (DOR) as Per BIRC Assessment	From first documented response to first documented progression or death, planned to be assessed up to 37 months	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.
Randomized Part: Time to Response (TTR) as Per BIRC Assessment	From randomization to first documented response, planned to be assessed up to 37 months	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.
Randomized Part: Disease Control Rate (DCR) as Per BIRC Assessment	Planned to be assessed up to 37 months	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.
Randomized Part: Progression-Free Survival After Next Line of Treatment (PFS2) as Per Investigator Assessment	Planned to be assessed up to 37 months	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.
Randomized Part: Maximum Plasma Concentration (Cmax) of Capmatinib	Pre-dose on Day 1 of Cycles 1, 2, 3, 4 and 6 (Cycle = 21 days)	Cmax of capmatinib calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Randomized Part: Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolites	Pre-dose on Day 1 of Cycles 1, 2, 3, 4 and 6 (Cycle = 21 days)	Cmax of osimertinib and its metabolites (AZ5104 and AZ7550) calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Randomized Part: Overall Survival (OS)	From randomization to date of death, planned to be assessed up to 37 months	OS was defined as the time from date of randomization to date of death due to any cause.
Randomized Part: Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (EORTC QLQ-C30) Score	Cycle 1 Day 1, Cycle 3 Day 1, then every 6 weeks for the 18 months after Cycle 1 Day 1 and every 12 weeks thereafter, until end of treatment, end of treatment and 6, 12 and 18 weeks post-progression (Cycle = 21 days)	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.
Randomized Part: Change From Baseline in the EORTC QLQ Lung Cancer Module (EORTC QLQ-LC13) Score	Cycle 1 Day 1, Cycle 3 Day 1, then every 6 weeks for the 18 months after Cycle 1 Day 1 and every 12 weeks thereafter, until end of treatment, end of treatment and 6, 12 and 18 weeks post-progression (Cycle = 21 days)	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.
Randomized Part: Change From Baseline in the EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Score	Cycle 1 Day 1, Cycle 3 Day 1, then every 6 weeks for the 18 months after Cycle 1 Day 1 and every 12 weeks thereafter, until end of treatment, end of treatment and 6, 12 and 18 weeks post-progression (Cycle = 21 days)	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.
Randomized Part: Change From Baseline in the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy (NCCN FACT)-Brain Symptom Index Version 2.0 (FBrSI)	Cycle 1 Day 1, Cycle 3 Day 1, then every 6 weeks for the 18 months after Cycle 1 Day 1 and every 12 weeks thereafter, until end of treatment, end of treatment and 6, 12 and 18 weeks post-progression (Cycle = 21 days)	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.
Randomized Part: Time to Symptom Deterioration for EORTC QLQ-C30 Questionnaire	From baseline to symptom deterioration, planned to be assessed up to 37 months	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.
Randomized Part: Time to Symptom Deterioration for EORTC QLQ-LC13 Questionnaire	From baseline to symptom deterioration, planned to be assessed up to 37 months	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.
Randomized Part: Time to Symptom Deterioration for NCCN FBrSl Questionnaire	From baseline to symptom deterioration, planned to be assessed up to 37 months	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.
Randomized Part: Duration of Intracranial Response (DOIR) Based on BIRC	From the date of first documented intracranial response to first documented intracranial progression or death, planned to be assessed up to 37 months	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.
Randomized Part: Time to Intracranial Response (TTIR) Based on BIRC	From randomization to first documented response, planned to be assessed up to 37 months	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.
Randomized Part: Intracranial Disease Control Rate (IDCR) Based on BIRC	Planned to be assessed up to 37 months	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.

Countries

Japan, Singapore, South Korea

Participant flow

Recruitment details

In the run-in part, participants were enrolled at 4 investigative sites in 3 countries. The study was terminated early based on Sponsor's decision unrelated to any safety concerns and the randomized part of the study was not initiated.

Pre-assignment details

A total of 23 participants were screened of which 6 participants were enrolled into the run-in part of the study.

Participants by arm

Arm	Count
Run-in Part: Capmatinib + Osimertinib Participants received a starting dose of capmatinib 400 mg, orally, twice daily (BID) in combination with osimertinib 80 mg, orally, once daily (QD)	6
Total	6

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	1
Overall Study	Progressive Disease	4
Overall Study	Study Terminated by Sponsor	1

Baseline characteristics

Characteristic	Run-in Part: Capmatinib + Osimertinib
Age, Continuous	61.7 years STANDARD_DEVIATION 7.76
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	6 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	0 Participants
Sex: Female, Male Female	4 Participants
Sex: Female, Male Male	2 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	1 / 6
other Total, other adverse events	5 / 6
serious Total, serious adverse events	2 / 6

Outcome results

Primary

Randomized Part: Progression Free Survival (PFS) Based on BIRC Assessment

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.

Time frame: From randomization to first documented progression or deaths, planned to be assessed up to 37 months

Population: 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.

Primary

Run-in Part: Number of Participants With Dose Limiting Toxicities (DLTs)

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.

Time frame: Up to 21 Days

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Run-in Part: Capmatinib + Osimertinib	Run-in Part: Number of Participants With Dose Limiting Toxicities (DLTs)	0 Participants

Secondary

Randomized Part: Change From Baseline in the EORTC QLQ Lung Cancer Module (EORTC QLQ-LC13) Score

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.

Time frame: Cycle 1 Day 1, Cycle 3 Day 1, then every 6 weeks for the 18 months after Cycle 1 Day 1 and every 12 weeks thereafter, until end of treatment, end of treatment and 6, 12 and 18 weeks post-progression (Cycle = 21 days)