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Participants who are asymptomatic and without prior brain therapy

Participants who are symptomatic with or without prior brain therapy or asymptomatic with prior brain therapy or with leptomeningeal disease

Capmatinib

Novartis Pharmaceuticals

The purpose of this study is to establish the intracranial efficacy of single agent capmatinib in the population of treatment-naïve or pretreated with one or two prior lines of systemic therapies for advanced stage Non Small-Cell Lung Cancer (NSCLC) with MET exon 14 mutation that has metastasized to the brain.

Cohort 1 (asymptomatic brain metastases (BM) without prior brain therapy) has been selected to identify patients who are most likely to benefit from capmatinib therapy in this setting and to establish a clinically relevant response outcome.

Cohort 2 is a heterogeneous group of patients (symptomatic with and without prior brain therapy, asymptomatic with prior brain therapy, or with leptomeningeal disease.), and the outcomes will be descriptive only

This is a prospectively designed, multicenter, open-label, two-cohort, phase II study to evaluate the intracranial efficacy of single agent capmatinib in participants with MET exon 14 mutated NSCLC and BM. Participants can be treatment naïve or pretreated with one or two prior lines of systemic therapies for advanced stage (stage IIIb - IV) NSCLC.

Approximately 60 participants will be enrolled globally and allocated to one of two cohorts:

Cohort 1 will enroll approximately 40 participants who are asymptomatic and without prior brain therapy.

Cohort 2 will enroll approximately 20 participants who are symptomatic with or without prior brain therapy or asymptomatic with prior brain therapy or with leptomeningeal disease.

All participants will be pre-screened for MET mutation and presence of BM will be documented at baseline by a radiologist/neuroradiologist.

Intracranial disease will be assessed and response to treatment will be evaluated using the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria every 8 weeks. Extracranial and whole body disease will be assessed and response to treatment will be evaluated using RECIST 1.1 every 8 weeks.

Participants will receive capmatinib 400 mg b.i.d. until they experience any of the following: documented disease progression by RANO-BM criteria and/or RECIST 1.1 (as assessed by the investigator and confirmed by BIRC), withdrawal of consent, pregnancy, lost to follow-up, or death.

For all participants, treatment with capmatinib may be continued beyond initial progression disease (PD) as per RANO-BM criteria and/or 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.

Approximately 60 participants will be enrolled globally and allocated to one of two cohorts based on whether their metastatic brain disease is symptomatic or asymptomatic and with or without prior brain therapy or if they have been diagnosed with leptomeningeal disease

A Phase II, Open-Label, Multicenter Study of Capmatinib in Subjects With MET Exon 14 Skipping Mutation Positive, Advanced, NSCLC With Brain Metastases

A Phase II, Open-Label, Multicenter Study of Capmatinib in Subjects With MET Exon 14 Skipping Mutation Positive, Advanced, Non Small-Cell Lung Cancer That Has Metastasized to the Brain

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

Overall Intracranial Response Rate (OIRR) in Cohort 1, defined as the proportion of participants with a confirmed best intracranial overall response of Complete Response (CR) or Partial Response (PR) per RANO-BM criteria as assessed by BIRC review

Overall Intracranial Response Rate (OIRR) in Cohort 1, defined as the proportion of participants with a confirmed best intracranial overall response of Complete Response (CR) or Partial Response (PR) per RANO-BM criteria as assessed by investigator review

Intracranial Disease Control Rate (IDCR) per RANO-BM criteria as assessed by investigator review and by BIRC review

Time to intracranial tumor Response (TTIR) per RANO-BM criteria as assessed by investigator review and by BIRC review

Duration of Intracranial Response (DOIR) per RANO-BM as assessed by investigator review and by BIRC review

Overall Intracranial Response Rate (OIRR) per RANO-BM criteria in Cohort 2 by investigator review and by BIRC review

Overall Extracranial Response Rate (OERR) per RECIST 1.1 by investigator review and by BIRC review

Extracranial Disease Control Rate (EDCR) per RECIST 1.1 by investigator and BIRC review

Time to Extracranial Response (TTER) per RECIST 1.1 by investigator review and by BIRC review

Duration of Extracranial Response (DOER) per RECIST 1.1 by investigator review and by BIRC review

Overall Response Rate (ORR) in the whole body per RECIST 1.1 by investigator review and by BIRC review

Time to response (TTR) in the whole body per RECIST 1.1 by investigator review and by BIRC review

Duration of response (DOR) in the whole body per RECIST 1.1 by investigator review and by BIRC review

Progression free survival (PFS) in the whole body per RECIST 1.1 by investigator review and by BIRC review

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

Safety profile of capmatinib. Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) including any clinically significant lab, vital signs, ECG abnormalities that are captured as an AE

Tolerability measured by the number of subjects who have interruptions of study treatment

Tolerability measured by the number of subjects who have reductions of study treatment

Tolerability measured by the dose intensity of study drug computed as the ratio of actual cumulative dose received and actual duration of exposure

Time to deterioration in symptoms of brain metastases in Cohort 1 with the Functional Assessment of Cancer Therapy (FACT)-Brain Symptom Index (FBrSI) (a standardized questionnaire developed to assess the quality of life of cancer patients)

Change from baseline in symptoms of brain metastases in Cohort 2 with the FACT-Brain Symptom Index (FBrSI) (a standardized questionnaire developed to assess the quality of life of cancer patients)

Change from baseline in lung cancer related symptoms, functioning and other domains of HRQoL in both cohorts with the EORTC QLQ-C30 (a 30-item questionnaire developed to assess the quality of life of cancer patients)

Change from baseline in lung cancer related symptoms, functioning and other domains of HRQoL in both cohorts with the QLQ-LC13 (a 13-item questionnaire developed to assess the quality of life of cancer patients)

Change from baseline in lung cancer related symptoms, functioning and other domains of HRQoL in both cohorts with the EQ-5D-5L (a standardized questionnaire developed to assess the quality of life of cancer patients)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Phase II, Open-Label, Multicenter Study of Capmatinib in Subjects With MET Exon 14 Skipping Mutation Positive, Advanced, NSCLC With Brain Metastases	NCT04460729	Non-small Cell ...	Capmatinib	18 Years -	Novartis
A Phase II, Open-Label, Multicenter Study of Capmatinib in Subjects With MET Exon 14 Skipping Mutation Positive, Advanced, NSCLC With Brain Metastases	NCT04460729	Non-small Cell ...	Capmatinib	18 Years -	Novartis

Spots Global Cancer Trial Database for treatment of lung cancer after first metastasi