Central Nervous System Efficacy of Capmatinib in NSCLC With Brain Metastases With cfDNA Positive MET Alterations

NCT05567055 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: HCC 22-010
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a phase II single-arm open label trial to evaluate the intracranial efficacy of capmatinib in advanced stage NSCLC with asymptomatic BM with positive MET amplification or METΔex14 detected on cfDNA.

Conditions

Non-small Cell Lung Cancer

Keywords

cfDNA positive MET alterations; MET amplification; METΔex14 mutation

Outcome Measures

Primary Outcomes (1)

• CNS Overall response rate (CORR) in

  Proportion of participants in with confirmed central nervous system complete response (CR) and/or partial response (PR) per RANO-BM criteria. CR: complete disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks; no new lesions; and stable or improved non-enhancing (T2/FLAIR) lesions. PR: ≥50% decrease, compared with baseline; the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks; no progression of non-measurable disease; no new lesions; stable or improved non-enhancing (T2/FLAIR) lesions on the same or a lower dose of corticosteroids compared with baseline scan; and the patient being on a corticosteroid dose not greater than the dose at time of the baseline scan and stable or improved clinically.

  Up to 36 months

Secondary Outcomes (9)

• CNS Duration of response (DOR)

  Up to 36 months

• CNS Progression-free survival (PFS)

  Up to 36 months

• CNS Overall response rate (CORR) (in cfDNA MET ex14 positive)

  Up to 36 months

• Systemic Duration of Response (DOR)

  Up to 36 months

• Systemic Progression-free Surivial (PFS)

  Up to 36 months

Study Arms (1)

Capmatinib

EXPERIMENTAL

400 mg orally, twice daily

Drug: Capmatinib

Interventions

Capmatinib DRUG

Capmatinib is a medication for the treatment of metastatic non-small cell lung cancer tumors that have a mutation that leads to the exon 14 skipping of the MET gene, which codes for the membrane receptor HGFR

Also known as: Tabrecta

Capmatinib

Eligibility Criteria

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

You may qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act in the US, European Union \[EU\] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Age \>18 years at time of study entry.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate normal organ and marrow function as defined below:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L without growth factor support
• Platelets ≥ 100 x 109/L
• Hemoglobin (Hgb) ≥ 9 g/dL
• Calculated creatinine clearance (using Cockcroft-Gault formula) ≥ 45 mL/min
• Total bilirubin (TBIL) ≤ 1.5 x ULN (upper limit of normal)
• Aspartate transaminase (AST) ≤ 3 x ULN, except for patients with liver metastasis, who may only be included if AST ≤ 5 x ULN
• Alanine transaminase (ALT) ≤ 3 x ULN, except for patients with liver metastasis, who may only be included if ALT ≤ 5 x ULN
• Alkaline phosphatase (ALP) ≤ 5.0 x UL
• Asymptomatic serum amylase ≤ Grade 2. Patients with Grade 1 or Grade 2 serum amylase at the beginning of the study must be confirmed to have no signs and/or symptoms suggesting pancreatitis or pancreatic injury (e.g. elevated P-amylase, abnormal imaging findings of pancreas, etc.)
• Serum lipase ≤ ULN
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

You may not qualify if:

• Treatment with prior MET tyrosine kinase inhibitor or HGF-targeting therapy. Treatment with other MET targeted therapies such as monoclonal antibodies may be allowed at the discretion of the PI.
• Prior SRS or WBXRT without evidence of CNS progression.
• Participants who are receiving concomitant corticosteroids must be on a stable or decreasing dose for at least 1 month prior to the first dose of study treatment. If patients are on corticosteroids for endocrine deficiencies or tumor-associated symptoms other than CNS related, dose must have been stabilized (or decreasing) for at least 5 days before first dose of capmatinib. Note: dose of steroids must be stable for 5 days before the baseline brain MRI.
• Patient with symptomatic brain metastases or leptomeningeal disease are excluded. Patients with asymptomatic leptomeningeal disease may be allowed at the principal investigator's discretion.
• Participants with other known targetable molecular alterations (such as ROS1, RET, NTRK1-3 translocations or BRAF mutation) who might be candidates to alternative targeted therapies as applicable per local regulations and treatment guidelines
• Participants with EGFR mutant and ALK fusion positive NSCLC are excluded.
• Presence or history of interstitial lung disease 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:
• Unstable angina within 6 months prior to screening
• Myocardial infarction within 6 months prior to screening
• History of documented congestive heart failure (New York Heart Association functional classification III-IV)
• Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, with or without antihypertensive medication. Initiation or adjustment of antihypertensive medication(s) is allowed prior to enrolment
• Ventricular arrhythmias
• Supraventricular and nodal arrhythmias not controlled with medication
• Other cardiac arrhythmia not controlled with medication

Sponsors & Collaborators

• Timothy Burns, MD, PHD: lead
• Novartis: collaborator

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

capmatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Timothy F Burns, MD, PhD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: September 30, 2022
• First Posted: October 5, 2022
• Study Start: October 3, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2028
• Last Updated: June 17, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share