Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Merestinib at the recommended phase II dose of 120 mg by mouth daily.

Merestinib is a potent and selective type II MET/RON kinase inhibitor with the ability to achieve inhibition of MET activity both in vitro and in vivo.

Merestinib

Mark Awad, MD

This research study is examining merestinib (a targeted therapy) as a possible treatment for non-small cell lung cancer (NSCLC) that was found to have a specific change in the MET gene (a MET exon 14 mutation); or as a treatment for solid tumors that have an alteration in the NTRK gene (an NTRK1, 2, or 3 rearrangement).

This is an open-label, phase II study of merestinib in patients with advanced NSCLC with a MET exon 14 mutation or patients with advanced cancer harboring an NTRK1, 2, or 3 rearrangement. Twenty patients with a MET mutation will be evaluated in a single-arm design. A small separate cohort of 5 NTRK patients will be evaluated for exploratory purposes.

Merestinib (LY2801653) is a small molecule that has been shown in vitro to be a reversible type II ATP-competitive inhibitor of MET. Pre-clinical testing also has shown merestinib to inhibit several other receptor tyrosine oncokinases including MST1R, FLT3, AXL, MERTK, TEK, ROS1, NTRK1/2/3, and DDR1/2 and the serine/threonine kinases MKNK1/2.

Merestinib In Non-Small Cell Lung Cancer And Solid Tumors

A Phase II Study of Merestinib in Non-Small Cell Lung Cancers Harboring MET Exon 14 Mutations and Solid Tumors With NTRK Rearrangements

ORR was defined as the proportion of participants achieving complete response (CR) or partial response (PR) as best response on treatment in MET Exon 14 Cohort based on RECISTv1.1 criteria.

OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

PFS based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) defined per RECIST 1.1 criteria. or death, or is censored at time of last disease assessment.

DOR, estimated using the Kaplan Meier method, is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) per RECISTv1.1, until the first date that recurrent or progressive disease is objectively documented. Patients without PD are censored at the date of last disease assessment.

All grade 4-5 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 that are not resolved in accordance with treatment guidelines were counted. Rate is the proportion of treated participants experiencing at least one of these adverse events as defined during the time of observation.

Eli Lilly and Company

Dana-Farber Cancer Institute

Principal Investigator

Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.

Merestinib: Oral, predetermined dosage of 120mg per protocol, once daily per 28 day treatment cycle

NSCLC (Met Exon 14 Mutation)

Solid Tumor (NTRK1,2,3 Rearrangement)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

No patient was accrued in the solid tumor arm.

Mark Awad, MD, PhD

The analysis population is comprised of eligible and treated patients.

Overall Response Rate (ORR) - MET Exon 14 Cohort

Median Overall Survival (OS) - MET Exon 14 Cohort

The analysis population is comprised of all eligible and treated patients.

Median Progression-free Survival (PFS) - MET Exon 14 Cohort

This analysis dataset is comprised of all patients who had a CR or PR on treatment.

Median Duration of Response (DOR) - MET Exon 14 Cohort

This analysis dataset is comprised of all eligible and treated patients.

Grade 4-5 Treatment-related Toxicity Rate

Merestinib: Oral, predetermined dosage of 120 mg per protocol, once daily per 28 day treatment cycle

Overall Study

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Docetaxel

Methotrexate

Mitogens

Tubulin Modulators

Antimitotic Agents

400mg of capmatinib tablets, administered orally twice daily

Docetaxel 75 mg/m2 solution administered by intravenous infusion on Day 1 of every 21-day cycle

400mg of capmatinib tablets administered orally twice daily

Capmatinib

Docetaxel 75 mg/m2 by intravenous infusion every 21 days

Novartis Pharmaceuticals

The purpose of the study is to learn whether the study drug (capmatinib) helps to control lung cancer better compared to a single agent chemotherapy (docetaxel) and whether it is safe when given to patients suffering from a particular type of lung cancer. This type of cancer is called non-small cell lung cancer (NSCLC) with certain specific genetic alterations (called mutations) of a gene called MET, within a specific part of the gene called exon 14.

Approximately 90 patients with advanced or metastatic lung cancer, with these specific mutations in the MET gene but without changes in their epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genes, will be enrolled in this study. Participants will be randomly assigned to get either capmatinib or docetaxel in a 2 to 1 ratio. The randomization will be stratified by prior lines of systemic therapy received for advanced/metastatic disease (one line vs. two lines).

During treatment, visits will be scheduled every 21 days.

For all participants, the respective treatment (either with capmatinib or docetaxel) may be continued beyond initial disease progression as per RECIST 1.1 (as assessed by the investigator and confirmed by BIRC) if, in the judgment of the investigator, there is evidence of clinical benefit, and the participant wishes to continue on the study treatment. After treatment discontinuation, all participants will be followed for safety evaluations during the safety follow-up period, and the participant's status will be collected every 12 weeks as part of the survival follow-up.

Participants randomized to docetaxel treatment will be eligible to crossover to receive capmatinib treatment after BIRC-confirmed, RECIST 1.1-defined progressive disease and after meeting the eligibility criteria prior to crossover.

Participants randomized to docetaxel treatment will be eligible to crossover to receive capmatinib treatment after blinded independent review committee (BIRC)-confirmed, RECIST 1.1- defined disease progression.

Study of Capmatinib Efficacy in Comparison With Docetaxel in Previously Treated Participants With Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation

A Phase III, Randomized, Controlled, Open-label, Multicenter, Global Study of Capmatinib Versus SoC Docetaxel Chemotherapy in Previously Treated Patients With EGFR wt, ALK Negative, Locally Advanced or Metastatic (Stage IIIB/IIIC or IV) NSCLC Harboring MET Exon 14 Skipping Mutation (METΔex14).

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Progression free survival is defined as the time from the date of randomization to the date of the first documented progression assessed by BIRC according to RECIST 1.1, or death due to any cause

Percentage of participants with confirmed best overall response (BOR) of complete response (CR) or partial response (PR), assessed by BIRC according to RECIST 1.1.

Percentage of participants with confirmed BOR of CR or PR, assessed by local review according to RECIST 1.1.

Time from date of randomization to first documented response of either CR or PR, which must be subsequently confirmed, assessed by BIRC according to RECIST 1.1.

Time from date of randomization to first documented response of either CR or PR, which must be subsequently confirmed, assessed by local review according to RECIST 1.1.

Time from the date of first documented response (CR or PR) to the first documented progression by BIRC per RECIST 1.1 or death due to any cause.

Time from the date of first documented response (CR or PR) to the first documented progression by local review per RECIST 1.1 or death due to any cause.

Percentage of participants with a BOR of confirmed CR, PR and stable disease (SD) assessed by BIRC according to RECIST 1.1

Percentage of participants with a BOR of confirmed CR, PR and SD assessed by local review according to RECIST 1.1

Time from the date of randomization to the date of the first documented progression assessed by local review according to RECIST 1.1, or death due to any cause

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

Percentage of participants with confirmed best overall intracranial response (BOIR) of CR or partial response (PR), as assessed by BIRC review per RANO-BM criteria.

Time from date of first documented intracranial response (CR or PR) to first documented intracranial progression per RANO-BM assessed by BIRC or date of death due to underlying cause of cancer.

Time from date of randomization to first documented intracranial response of either CR or PR, per RANO-BM criteria and assessed by BIRC, which must be subsequently confirmed.

Percentage of participants with a BOR of confirmed CR, PR and stable disease (SD) (or non-CR/non-PD) per RANO-BM, assessed by BIRC.

Plasma concentrations of capmatinib. Blood samples will be collected at indicated time points for pharmacokinetic analysis.

EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. The questionnaire is composed of both multi-item scales and single-item measures based on the participants experience over the past week. These include five domains (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/HRQoL scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

Change from baseline in EORTC QLQ-C30 scores will be assessed

EORTC QLQ-LC13 is a 13-item lung cancer specific questionnaire. The five domains of the questionnaire 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 is score based on its presence, hence yes or no. A higher score indicates a higher presence of symptoms.

Change from baseline in EORTC QLQ-LC13 scores will be assessed

EQ-5D-5L is a standardized measure to assess the overall health-related quality of life in patients. The EQ-5D-5L consists of 2 parts- 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), each with 5 levels: from 1 (no problems) to 5 (extreme problems). The EQ VAS is a self-perceived health score assessed using a visual analogue scale that ranges from 0 (the worst imaginable health) to 100 (the best imaginable health), with higher scores indicating higher health utility.

Change from baseline in EQ-5D-5L scores will be assessed

EORTC QLQ-LC13 is a 13-item lung cancer specific questionnaire. The five domains of the questionnaire 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 is score based on its presence, hence yes or no. A higher score indicates a higher presence of symptoms.

Time to symptom deterioration for chest pain, cough and dyspnea will be assessed

EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. The questionnaire is composed of both multi-item scales and single-item measures based on the participants experience over the past week. These include five domains (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/HRQoL scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

Time to deterioration in QoL from EORTC-QLQ-C30 will be assessed.

Participants received one or two prior lines of treatment

400 mg of capmatinib tablets, administered orally twice daily

The purpose of the study is to learn whether the study treatment (capmatinib), which already shows efficacy and safety in non-Chinese patients, could help Chinese patients with controlling their lung cancer in a safe way. Participants will have a type of lung cancer called non-small cell lung lancer (NSCLC), with a specific alteration in a part of their DNA (called mutation) of the MET gene, within a specific part of this gene called exon 14.

Participants who have advanced (or metastatic) non-small cell lung cancer with specific mutations in the MET gene but without mutations in the EGFR or ALK genes, who are aged 18 years or older will be enrolled in this study.

The study drug, capmatinib (also known as INC280), is an oral drug that is called a 'targeted' medicine, which means it targets particular processes that may not be working properly in cancer cells (called dysregulation). The dysregulation of the MET signaling in cancer cells of patients with NSCLC is believed to make the cancer worse. Capmatinib has been shown to selectively block the effects of the MET gene and therefore may help in keeping the disease under control, stopping cancer cells from growing.

This is an open-label, multicenter two-cohort phase II study. Chinese adult participants with EGFR wild-type (wt) (EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 L858R substitution mutations), anaplastic lymphoma kinase (ALK) rearrangement negative, advanced (stage IIIB, IIIC or IV) NSCLC disease harboring MET exon 14-skipping (METΔex14) mutations as determined by a Novartis central molecular laboratory will be treated in this study. Cohort 1 will include treatment naive participants and Cohort 2 participants who failed one or two prior lines of therapy in the advanced stage (stage IIIB, IIIC or IV). Each participant will receive 400 mg capmatinib tablet twice daily (BID).

The primary endpoint is the overall response rate (ORR) by cohort as per the blinded independent review committee (BIRC) review. ORR is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR) according to RECIST 1.1.

The primary analysis will be performed using full analysis set (FAS). The primary efficacy endpoint ORR will be estimated and the exact 95% confidence interval (CI) will be provided by cohort.

Study of Capmatinib in Chinese Adult Patients With Advanced Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation

A Phase II, Multicenter, Two-cohort Study of Oral MET Inhibitor Capmatinib in Chinese Adult Patients With EGFR Wild-type (wt), ALK Rearrangement Negative, MET Exon 14 Skipping Mutations, Advanced Non-small Cell Lung Cancer (NSCLC) Who Are Treatment Naive or Failed One or Two Prior Lines of Systemic Therapy

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

ORR is defined as the proportion of participants with a best overall response (BOR) defined as complete response or partial response (CR+PR) by BIRC assessment per RECIST 1.1

DOR, calculated as the time from the date of the first documented CR or PR by BIRC per RECIST 1.1 to the first documented progression or death due to any cause for participants with PR or CR

ORR (CR+PR) and DOR per RECIST 1.1 by investigator assessment

TTR, calculated as the time from first dose of capmatinib to first documented response (CR+PR) for participants with PR or CR per RECIST 1.1 by BIRC and investigator

DCR, calculated as the proportion of participants with BOR of CR, PR, or SD (stable disease) per RECIST 1.1 by BIRC and investigator

PFS, defined as time from first dose of capmatinib to progression or death due to any cause per RECIST 1.1 by BIRC and investigator

OS is defined as the time from first dose to the date of death due to any cause.

Overall intracranial response rate (OIRR) calculated as the proportion of participants with a confirmed best overall intracranial response (BOIR) of CR or PR per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria as assessed by BIRC

Intracranial disease control rate (IDCR), defined as the proportion of participants with a confirmed BOIR of CR or PR or SD (or non-CR/non-Progressive Disease) per RANO-BM criteria as assessed by BIRC review.

Time to intracranial response (TTIR) defined as the time from the date of the start of study treatment to the date of the first documented intracranial response of either CR or PR per RANO-BM criteria as assessed by BIRC

Duration of intracranial response (DOIR) 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 date of death due to any cause.

ORR, DOR and PFS per RECIST 1.1 for participants by MET mutation status assessed in circulating tumor DNA (ctDNA) at baseline, both by BIRC and investigator. The association between MET mutation status as measured in ctDNA at baseline with ORR, DOR and PFS will be established using Kaplan-Meier curve by cohort separately. Median survival together with their 95% confidence intervals will be reported.

Steady state Ctrough and steady state 0.5- 1.5 hour and 3-5 hours post-dose concentrations

EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients.

EORTC QLQ-LC13 is a 13-item lung cancer specific questionnaire.

EQ-5D-5L is a standardized measure to assess the overall health-related quality of life in patients.

National Comprehensive Cancer Network Functional Assessment of Cancer Therapy (NCCN FACT) - Brain Symptom Index version 2.0 (FBrSI) symptom module, consisting of 24 items with a recall period of the past 7 days, will explore changes in symptoms associated with potential brain metastases.

Spartalizumab

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

capmatinib in combination with spartalizumab

spartalizumab placebo

A double-blind, placebo controlled, randomized, phase II study evaluating the efficacy and safety of capmatinib (INC280) and spartalizumab (PDR001) combination therapy versus capmatinib and placebo as first line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) patients with MET exon 14 skipping (METΔex14) mutations

The purpose of this study was to evaluate the efficacy and safety of capmatinib in combination with spartalizumab in treatment naive patients with EGFR wild-type, ALK rearrangement negative advanced NSCLC, harboring METΔex14 mutations.

A run-in part (Part 1) was conducted to determine the anti-tumor activity and safety of capmatinib in combination with spartalizumab. Upon review of safety data and confirmation of anti-tumor activity in Part 1, the randomized part (Part 2) was planned to be initiated to compare the efficacy and safety of capmatinib plus spartalizumab to capmatinib plus placebo.

Combined treatment of METΔex14 mutated NSCLC with capmatinib and spartalizumab was expected to result in improved efficacy compared to each single agent due to direct targeting of an oncogenic driver (MET) as well as more efficient stimulation of an anti-tumor immune response than with PD-1 blockade alone.

The study enrollment was halted on 28-Jul-2021 per sponsor's decision. The enrollment halt decision was based on lack of tolerability observed in capmatinib and spartalizumab combination treatment in the run-in part (Part 1) of the trial.

Following the study enrollment halt during Part 1 (Run in Part), Part 2 was not initiated.

Immediately following the enrollment halt:

* All ongoing subjects were discontinued from spartalizumab treatment and continue to receive single agent capmatinib
* Enrolled subjects who had not started study treatment were to receive capmatinib single agent treatment from the start

Run-in part: single arm, open-label.

Randomized part: two-arms parallel assignment, double-blinded, placebo control

Study of Capmatinib and Spartalizumab/Placebo in Advanced NSCLC Patients With MET Exon 14 Skipping Mutations

A Double-blind, Placebo Controlled, Randomized, Phase II Study Evaluating the Efficacy and Safety of Capmatinib and Spartalizumab vs Capmatinib and Placebo as 1st Line Treatment for Advanced NSCLC Patients With MET exon14 Skipping Mutations

Tumor response was based on local investigator assessment as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. ORR per RECIST v1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR).

For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. Tumor response based on blinded independent review committee (BIRC) assessment per RECIST v1.1.

Number of participants with at least one dose reduction of capmatinib and number of participants with at least one dose interruption of capmatinib.

Number of participants with at least one dose reduction of spartalizumab and number of participants with at least one dose interruption of spartalizumab. Dose reductions were not allowed for spartalizumab.

Dose intensity of capmatinib was calculated as actual cumulative dose in milligrams divided by duration of exposure in days.

Dose intensity of spartalizumab was calculated as actual cumulative dose in milligrams divided by duration of exposure in days and then multiplied by the duration of one cycle (28 days).

DCR is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), and non-CR/non-progressive disease (for subjects without target lesions). Tumor response was based on local investigator assessment per RECIST v1.1.

For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression).

PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on investigator assessment per RECIST v1.1. Progression is defined using RECIST v1.1 as at least 20% increase in the sum of diameters of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, the sum must also demonstrate an absolute increase of at least 5 mm.

PFS was analyzed using Kaplan-Meier estimates.

Pharmacokinetic (PK) parameters were calculated based on capmatinib plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.

PK parameters were calculated based on capmatinib plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose. Actual recorded sampling times were considered for the calculations.

PK parameters were calculated based on capmatinib plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUCtau calculation. A dosing interval (tau) is defined as 12 hours. The portion of area under the curve between 8 hours and 12 hours post-dose was calculated by extrapolation based on terminal elimination slop.

PK parameters were calculated based on capmatinib plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.

Pharmacokinetic (PK) parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.

PK parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.

PK parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUCtau calculation. A dosing interval (tau) is defined as 28 days.

PK parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.

OS is defined as the time from date of start of treatment to date of death due to any cause.

Number of participants with at least one dose reduction of capmatinib and spartalizumab and number of participants with at least one dose interruption of capmatinib and spartalizumab.

Dose intensity is defined as the ratio of actual cumulative dose and duration of exposure.

PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. Tumor response based on investigator assessment per RECIST v1.1.

DCR is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), and non-CR/non-progressive disease (for subjects without target lesions). Tumor response based on BIRC and local investigator assessment per RECIST v1.1.

ORR is defined as the percentage of participants with a best overall response of Complete Response (CR) and Partial Response (PR). Tumor response based on BIRC and local investigator assessment per RECIST v1.1.

DOR is defined as the time from the date of first documented response (CR or PR) to the first documented progression per RECIST 1.1 or death due to any cause.

TTR is defined as the time from the date of start of treatment to the first documented response of either CR or PR, which must be subsequently confirmed, according to RECIST 1.1.

The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items and is composed of both multi-item scales and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive, and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial impact) and a global health status/QoL scale. All scales and single-item measures range in score from 0 to 100. For the functional and the global QoL scales, a higher score indicates better health. For the symptom scales, a higher score indicates more symptom burden. The QLQ-C30 summary score (0-100) is calculated as the mean of 13 of the 15 QLQ-C30 scale and item scores (excluding global QoL and financial impact), with a higher score indicating a better health-related QoL.

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.

The EQ-5D-5L is a standardized measure of health utility that provides a single index value for one's health status. The EQ-5D-5L contains one item for each of five dimensions of health-related quality of life (HRQOL) (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Response options for each item vary from having no problems to extreme problems. Subject responses to the five dimensions of HRQOL reflect a specific health state that corresponds to a population preference weight for that state on a continuous scale of 0 (death) to 1 (perfect health). A visual analog scale (ranging from 0 to 100) is also included to capture subject's rating of their overall health status. Higher scores of the EQ-5D-5L represent better health states.

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 in chest, 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.

The time to definitive 10 points deterioration is defined as the time from the date of randomization to the date of event, which is defined as at least 10 points relative to baseline worsening of the corresponding scale score or death due to any cause.

The EORTC QLQ-C30 contains 30 items and is composed of both multi-item scales and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive, and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial impact) and a global health status/QoL scale. All scales and single-item measures range in score from 0 to 100. For the functional and the global QoL scales, a higher score indicates better health. For the symptom scales, a higher score indicates more symptom burden.

The time to definitive 10 points deterioration is defined as the time from the date of randomization to the date of event, which is defined as at least 10 points relative to baseline worsening of the corresponding scale score or death due to any cause.

Pharmacokinetic (PK) parameters calculated based on capmatinib and spartalizumab concentrations in plasma and serum, respectively, by using non-compartmental methods. Cmax is defined as the maximum (peak) observed concentration following a dose.

Pharmacokinetic (PK) parameters calculated based on capmatinib and spartalizumab concentrations in plasma and serum, respectively, by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) concentration following a dose.

Pharmacokinetic (PK) parameters calculated based on capmatinib and spartalizumab concentrations in plasma and serum, respectively, by using non-compartmental methods.

Immunogenicity (IG) evaluated in serum samples. The assay to quantify and assess the IG was a validated homogeneous enzyme-linked immunosorbent assay (ELISA).

Patients were analyzed according to the treatment they actually received.

Capmatinib 400 mg BID in combination with spartalizumab 400 mg Q4W before the discontinuation of spartalizumab

Run-in Part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W (Prior Discontinuing Spartalizumab)

Capmatinib 400 mg BID in combination with spartalizumab 400 mg Q4W after the discontinuation of spartalizumab

Run-in Part: Capmatinib 400mg BID + Spartalizumab 400mg Q4W (After Discontinuing Spartalizumab)

Immediately following the discontinuation of spartalizumab (and enrollment halt), enrolled subjects who had not started study treatment received capmatinib single agent treatment from the start

Run-in Part: Capmatinib 400mg BID Only

Capmatinib 400 mg orally twice daily (BID) in combination with spartalizumab 400 mg intravenously every 28 days (Q4W) in the run-in part.

Run-in Part: Capmatinib 400 mg BID + Spartalizumab 400 mg Q4W

Capmatinib 400 mg orally twice daily (BID) in combination with spartalizumab 400 mg intravenously every 28 days (Q4W) in the randomized part.

Randomized Part: Capmatinib 400 mg BID + Spartalizumab 400 mg Q4W

Capmatinib 400 mg orally twice daily (BID) in combination with spartalizumab matching placebo intravenously every 28 days (Q4W) in the randomized part.

Randomized Part: Capmatinib 400 mg BID + Placebo

Race/Ethnicity, Customized

All patients to whom study treatment had been assigned and who received at least one dose of study treatment (i.e. at least one dose of any component of the study treatment that is capmatinib or spartalizumab). The randomized part of the study was not initiated.

Study Director

All patients to whom study treatment had been assigned and who received at least one dose of study treatment (i.e. at least one dose of any component of the study treatment that is capmatinib or spartalizumab) in the single arm run-in part. Patients were analyzed according to the treatment they were assigned to.

Run-in Part: Overall Response Rate (ORR) by Investigator Assessment as Per RECIST 1.1

All patients to whom study treatment had been assigned and who received at least one dose of study treatment in the randomized part. The randomized part of the study was not initiated and data was not collected.

Randomized Part: Progression-Free Survival (PFS) by BIRC as Per RECIST 1.1

At least one dose reduction

At least one dose interruption

All patients to whom study treatment had been assigned and who received at least one dose of capmatinib in the single arm run-in part. Patients were analyzed according to the treatment they were assigned to.

Run-in Part: Number of Participants With Dose Reductions and Dose Interruptions of Capmatinib

All patients to whom study treatment had been assigned and who received at least one dose of spartalizumab in the single arm run-in part. Patients were analyzed according to the treatment they were assigned to.

Run-in Part: Number of Participants With Dose Reductions and Dose Interruptions of Spartalizumab

Run-in Part: Dose Intensity of Capmatinib

Run-in Part: Dose Intensity of Spartalizumab

Run-in Part: Disease Control Rate (DCR) by Investigator Assessment as Per RECIST 1.1

Run-in Part: Progression-Free Survival (PFS) by Investigator Assessment as Per RECIST 1.1

Patients in the capmatinib full pharmacokinetic analysis set (INC-FPAS) with an available value for the outcome measure. INC-FPAS consists of all patients who had an extensive PK sampling and provided a capmatinib evaluable PK profile on Cycle 3 Day 1.

Run-in Part: Maximum Observed Plasma Concentration (Cmax) of Capmatinib

Run-in Part: Time to Reach Maximum Plasma Concentration (Tmax) of Capmatinib

Run-in Part: Area Under the Plasma Concentration-time Curve From Time Zero to the End of a Dosing Interval (AUCtau) of Capmatinib

Run-in Part: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Capmatinib

Patients in the spartalizumab full pharmacokinetic analysis set (PDR-FPAS) with an available value for the outcome measure. PDR-FPAS consists of all patients who had an extensive PK sampling and provided a spartalizumab evaluable PK profile on Cycle 3.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Merestinib In Non-Small Cell Lung Cancer And Solid Tumors	NCT02920996	Carcinoma, Non-... Solid Tumor	Merestinib	18 Years -	Dana-Farber Cancer Institute
Study of Capmatinib Efficacy in Comparison With Docetaxel in Previously Treated Participants With Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation	NCT04427072	Carcinoma, Non-...	Capmatinib Docetaxel	18 Years -	Novartis
Merestinib In Non-Small Cell Lung Cancer And Solid Tumors	NCT02920996	Carcinoma, Non-... Solid Tumor	Merestinib	18 Years -	Dana-Farber Cancer Institute
Study of Capmatinib Efficacy in Comparison With Docetaxel in Previously Treated Participants With Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation	NCT04427072	Carcinoma, Non-...	Capmatinib Docetaxel	18 Years -	Novartis
Study of Capmatinib Efficacy in Comparison With Docetaxel in Previously Treated Participants With Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation	NCT04427072	Carcinoma, Non-...	Capmatinib Docetaxel	18 Years -	Novartis
Study of Capmatinib in Chinese Adult Patients With Advanced Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation	NCT04677595	Non-Small Cell ...	Capmatinib	18 Years -	Novartis
Study of Capmatinib in Chinese Adult Patients With Advanced Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation	NCT04677595	Non-Small Cell ...	Capmatinib	18 Years -	Novartis
Study of Capmatinib and Spartalizumab/Placebo in Advanced NSCLC Patients With MET Exon 14 Skipping Mutations	NCT04323436	Carcinoma, Non-...	Spartalizumab Capmatinib spartalizumab p...	18 Years -	Novartis
Real-Time Monitoring of Symptoms in Lung Cancer Patients Receiving Oral Targeted Therapies	NCT05370469	Lung Cancer EGFR Gene Mutat... EGFR ALK Gene Mutati... RET Gene Mutati... MET Gene Mutati... KRAS Mutation-R... BRAF ROS1 Gene Mutat...	Sensus Smartwat... RX Cap Fitbit Sense Surveys	18 Years -	University of Virginia
Study of Capmatinib and Spartalizumab/Placebo in Advanced NSCLC Patients With MET Exon 14 Skipping Mutations	NCT04323436	Carcinoma, Non-...	Spartalizumab Capmatinib spartalizumab p...	18 Years -	Novartis

Spots Global Cancer Trial Database for met mutation

Every month we try and update this database with for met mutation cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.