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

NCT04460729 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: CINC280A2203
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Non-small Cell Lung Carcinoma (NSCLC)

Keywords

Non-small cell lung carcinoma; Non-small cell lung cancer; NSCLC; Treatment of lung cancer after first metastasi; Lung cancer; Lung adenocarcinoma; Squamous cell lung carcinoma; Large-cell lung carcinoma; Large-cell lung cancer

Outcome Measures

Primary Outcomes (1)

• Overall Intracranial Response Rate (OIRR) in Cohort 1 by Blinded Independent Review Committee (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 BIRC review

  Up to 36 months

Secondary Outcomes (23)

• Overall Intracranial Response Rate (OIRR) in Cohort 1 by investigator review

  Up to 36 months

• Intracranial Disease Control Rate (IDCR) by investigator and BIRC review

  Up to 36 months

• Time to intracranial tumor Response (TTIR) by investigator and BIRC review

  Up to 36 months

• Duration of Intracranial Response (DOIR) by investigator and BIRC review

  Up to 36 months

• Overall Intracranial Response Rate (OIRR) in Cohort 2 by investigator and BIRC review

  Up to 36 months

Study Arms (2)

Cohort 1

EXPERIMENTAL

Participants who are asymptomatic and without prior brain therapy

Drug: Capmatinib

Cohort 2

EXPERIMENTAL

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

Drug: Capmatinib

Interventions

Capmatinib DRUG

400 mg administered orally twice daily

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed stage IV (according to Version 8 of the American Joint Committee on Cancer (AJCC)) NSCLC that is EGFR wt, ALK rearrangement negative as assessed by a validated test as part of the participant's standard of care and has MET∆ex14 mutation per Novartis-designated central laboratory or (US only) locally with FoundationOne Companion Diagnostic (F1CDx) .
• Treatment naïve or up to two prior lines of systemic therapy for stage IIIb-IV NSCLC
• Measurable intracranial lesions:
• Cohort 1 and Cohort 2 (without leptomeningeal carcinoma): At least 1 measurable intracranial lesion per RANO-BM criteria, documented by a radiologist/neuroradiologist (treated or untreated).
• Cohort 2 (with leptomeningeal carcinoma): participants with leptomeningeal carcinoma may not have measurable lesions. In this circumstance, the participant's disease will be considered to have non-target lesions only at baseline and their response based on descriptive clinical criteria by physician assessment.
• Capable of undergoing magnetic resonance imaging (MRI)
• ECOG performance status of 0 or 1

You may not qualify if:

• Only for Cohort 1: any neurological symptoms related to brain metastases
• For participants in Cohort 2 with prior brain therapy: Treatment with stereotactic radiosurgery within 14 days prior to the start of study treatment or treatment with WBRT within 14 days prior to the start of study treatment
• Prior treatment with any MET targeting therapy or HGF inhibitor
• Participants with other known druggable molecular alterations (such as ROS1 translocation or BRAF mutation) who might be candidates to alternative targeted therapies as applicable per local regulations and treatment guidelines
• Presence or history of ILD or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention)
• Clinically significant, uncontrolled heart diseases including History of familial long QT syndrome, sudden death or congenital long QT syndrome

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Adenocarcinoma of Lung

Interventions

capmatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: July 2, 2020
• First Posted: July 8, 2020
• Study Start: November 11, 2020
• Primary Completion: November 17, 2023
• Study Completion: November 17, 2023
• Last Updated: December 3, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share