AzTrials
AzTrials

Metastatic Lung Non-Small Cell CarcinomaPhase 1NCT05435846

Capmatinib Plus Trametinib for the Treatment of Metastatic Non-small Cell Lung Cancer With MET Exon 14 Skipping Mutation

A Phase 1 study testing Capmatinib and Trametinib in people with Metastatic Lung Non-Small Cell Carcinoma and Stage IV Lung Cancer, run by Collin Blakely at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This phase I/Ib trial studies the side effects and best doses of capmatinib plus trametinib when given together for the treatment of patients with MET exon 14 skipping mutation non-small cell lung cancer that has spread to other places in the body (metastatic). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Capmatinib and Trametinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
10 Aug 2022to 31 May 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants must have histologically or cytologically confirmed, non-small cell lung cancer.
  • Documented MET exon 14 skipping mutation by tumor DNA sequencing or cell-free DNA assay by Clinical Laboratory Improvement Act (CLIA) - approved laboratory AND previously received treatment with a MET inhibitor (capmatinib crizotinib, savolitinib, or tepotinib) with evidence of disease progression, in the opinion of the investigator.
  • Note - MET inhibitor therapy is NOT required to be the most recent anti-cancer therapy. Prior treatment with platinum-based chemotherapy or anti-programmed cell death protein 1 (PD-1) /programmed death-ligand 1 (PD-L1) therapy (alone or in combination with chemotherapy) is allowed, but not required.
  • - or (For dose escalation only): MET amplification or fusion detected in tumor sample or cell-free DNA by next generation sequencing (NGS) or Fluorescent in situ hybridisation (FISH) by CLIA-approved laboratory AND prior treatment with a MET inhibitor (capmatinib crizotinib, savolitinib, or tepotinib) with at least 5 months of clinical benefit, followed by disease progression, in the opinion of the investigator.
  • Archived tissue available or willingness to undergo new tumor biopsy.
  • Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
Show all 29Show fewer
  • Life expectancy of at least 3 months.
  • Age >= 18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (Karnofsky) > 60%.
  • Resolution of all acute toxic effects (other than alopecia, or non-clinically significant lab abnormalities) of prior chemotherapy, targeted therapy, immunotherapy, radiotherapy, or surgical procedures to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 grade 1.
  • Absolute neutrophil count >= 1,500/microliter (mcL)
  • Platelets >= 100,000/mcL
  • Hemoglobin (Hgb) >= 9 g/dl
  • Total bilirubin within 1.2 X institutional upper limit of normal, unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits.
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) =< 3 X institutional upper limit of normal if no known liver metastases.
  • Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase (SGPT)) =< 3 X institutional upper limit of normal if no known liver metastases.
  • Alkaline phosphatase (ALP) =< 5.0 X institutional upper limit of normal.
  • Creatinine =< 1.5 x within institutional upper limit of normal.
  • Creatinine glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2,calculated using the Cockcroft-Gault equation, unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2.
  • Asymptomatic serum amylase =< grade 2.
  • Asymptomatic serum amylase increase grade 1 and 2 are allowed if at the beginning of the study is 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 =< upper limits of normal (ULN).
  • Ability to understand a written informed consent document, and the willingness to sign it.
  • For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • Individuals with a history of hepatitis C virus (HCV) infection must have been treated and cured or currently be on treatment with an undetectable HCV viral load.
  • Individuals with treated brain metastases are eligible if follow-up brain imaging (within 1 month prior to first dose) after central nervous system (CNS)-directed therapy shows no evidence of progression and not on steroids.
  • Individuals with a prior or concurrent malignancy are eligible for this trial as long as they are not on active treatment and no active disease is present, and whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen. Exceptions: thyroid hormone replacement is allowed and adjuvant hormonal therapy for breast cancer is allowed.
  • Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 16 weeks after last administration of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 16 weeks after last administration of study treatment.

Who cannot join

  • Known activating mutations or oncogenic fusions in Epithelial Growth Factor Receptor (EGFR), KRAS g12c, ALK, ROS1, Neurotrophic tyrosine receptor kinase (NTRK), BRAF V600E, or RET or known on-target MET mutations on residues D1228 or Y1230.
  • For Phase I patients enrolling into dose levels 1 or -1, intolerability of prior treatment with capmatinib 300 mg BID requiring dose reduction or permanent discontinuation is exclusionary.
  • For Phase I patients enrolling into dose level -2, intolerability of prior treatment with capmatinib 200 mg BID requiring dose reduction or permanent discontinuation is exclusionary.
  • For Phase I patients enrolling into dose level 2, intolerability of prior treatment with capmatinib 400 mg BID requiring dose reduction or permanent discontinuation is exclusionary.
  • Phase Ib patients enrolling into the dose expansion cohort must have previously tolerated the RP2D of capmatinib if they have received prior capmatinib treatment.
  • Pregnant women are excluded from this study because capmatinib and trametinib are tyrosine kinase inhibitors (TKIs) with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with capmatinib and trametinib, breastfeeding should be discontinued if the mother is treated with capmatinib and trametinib.
Show all 30Show fewer
  • Patients who have received systemic anti-cancer therapies within the following time periods prior to the first dose of study drug: within 3 weeks of cytotoxic chemotherapy or antibody therapy, radiation within 2 weeks, targeted therapy within 7 days.
  • Note: Concomitant administration of Luteinizing hormone-releasing hormone (LHRH) analogues for prostate cancer and somatostatin analogues for neuroendocrine tumors are allowed as per standard of care. Patients who are currently receiving and progressing on capmatinib monotherapy will be allowed to continue treatment without interruption
  • History of interstitial lung disease or pneumonitis.
  • Note: History of radiation pneumonitis not requiring steroids is allowed.
  • Known Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) infection, or human immunodeficiency virus (HIV) with inadequate CD4+ T cell counts or a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections.
  • Note: Participants with laboratory evidence of cleared HBV and HCV infection will be permitted). Patients living with HIV, with adequate CD4+ T cell counts, and without a history of AIDS-defining opportunistic infections will be permitted.
  • Known active COVID-19 infection.
  • Note: Patients who have recovered from an infection and test negative for viral ribonucleic acid (RNA) will be allowed.
  • History or evidence of cardiovascular risk including any of the following:
  • Left ventricular ejection fraction (LVEF) < lower limit of normal (LLN) by echocardiogram (ECHO) or multigated acquisition scan (MUGA).
  • A QT interval corrected for heart rate using the Fridericia's formula (QTcF) 470 msec.
  • History or evidence of current clinically significant uncontrolled arrhythmias.
  • History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to study enrollment.
  • History or evidence of current >= Class II congestive heart failure as defined by New York Heart Association (NYHA).
  • Treatment refractory hypertension defined as a blood pressure of systolic > 150 mmHg and/or diastolic > 95 mm Hg which cannot be controlled by anti-hypertensive therapy.
  • Patients with intra-cardiac defibrillators.
  • Note: Participants with atrial fibrillation controlled (defined as not requiring change in cardiac drug dosing, emergency room visit, or hospital admission) for >30 days prior to dosing are eligible.
  • Is currently receiving any other investigational agents.
  • Hypersensitivity to capmatinib or trametinib or any of its excipients.
  • Patients with known history or current evidence of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED).
  • Major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks prior (2 weeks for resection of brain metastases) to starting study treatment or who have not recovered from side effects of such procedure.
  • Note: Video-assisted thoracic surgery (VATS) and mediastinoscopy will not be counted as major surgery and participants can be enrolled in the study >= 1 week after the procedure.
  • Participants receiving treatment with strong inducers of CYP3A that cannot be discontinued at least 1 week prior to the start of treatment with study treatment and for the duration of the study.
  • Any condition that in the opinion of the investigator would interfere with the participant's safety or compliance while on trial.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California San Francisco

    San Francisco, California, 94143

Other trials in United States

About this study

Official title: A Multicenter Phase I/Ib Study of Capmatinib Plus Trametinib in Patients With Metastatic MET Exon 14 Skipping Mutation Positive NSCLC

This phase I/Ib trial studies the side effects and best doses of capmatinib plus trametinib when given together for the treatment of patients with MET exon 14 skipping mutation non-small cell lung cancer that has spread to other places in the body (metastatic). Capmatinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Trametinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells. Capmatinib and trametinib are "targeted therapies." These targeted therapies work by detecting and targeting a mutation in the MET gene. Giving Capmatinib and trametinib may kill more tumor cells in patients with metastatic non-small cell lung cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To identify recommended phase II dose (RP2D) of capmatinib in combination with trametinib in non-small cell lung cancer (NSCLC) with MET 14 exon mutation, MET amplification, or MET fusion (Phase I).

II. To further characterize the safety profile of the RP2D of capmatinib in combination with trametinib in MET-exon14 mutated NSCLC (Phase Ib).

SECONDARY OBJECTIVES:

  1. To further characterize the safety profile of the combination of capmatinib and trametinib in NSCLC with MET exon 14 mutation, MET amplification, or MET fusion (Phase I).

II. To determine preliminary efficacy ofcapmatinib in combination with trametinib in MET-exon14 mutated NSCLC (Phase Ib)

EXPLORATORY OBJECTIVES:

  1. To evaluate the pharmacokinetics of capmatinib in combination with trametinib.

II. To identify biomarkers of response to capmatinib and trametinib. III. To identify mechanisms of resistance tocapmatinib and trametinib.

OUTLINE: This is a phase I dose-escalation study of capmatinib and trametinib followed by a phase Ib dose expansion study.

Patients receive capmatinib orally (PO) twice daily (BID) and trametinib PO once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 12 months

Being tested
Capmatinib, Trametinib
Keywords
MET exon 14 skipping mutation, Mutation Positive
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CapmatinibDrug

    Also called INC280

    Given orally

  • TrametinibDrug

    Also called TMT212, Mekinist

    Given orally

Study groups in NCT05435846
Study groupRoleWhat they receive
Phase 1: Dose EscalationExperimentalPatients receive 200 - 400 mg capmatinib orally, twice a day and 1.0 or 1.5 mg trametinib orally once a day on days 1-28 of each cycle. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Capmatinib; Drug: Trametinib
Phase 1b: Dose ExpansionExperimentalPatients will receive the recommended phase 2 dose (RP2D) or capmatinib in combination with trametinib determined by the safety profile of the Phase 1 group. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Capmatinib; Drug: Trametinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of participants with reported dose limiting toxicity (DLT) (Phase I)

    Proportion of participants who experience a DLT for capmatinib in combination with trametinib in Phase I. A dose limiting toxicity (DLT) will be defined as any adverse event that are considered by the investigator to be at least possibly related to capmatinib or trametinib and are observed during the first 28 days of treatment (Cycle 1).

    Measured: 1 cycle (each cycle is 28 days)

  2. Proportion of participants with treatment-emergent adverse events (Phase Ib)

    Proportion of participants with treatment-emergent Adverse Events, will be reported as preferred terms using Medical Dictionary for Regulatory Activities (MedDRA).as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0) in Phase Ib (Dose Expansion).

    Measured: Up to 12 months

Secondary outcomes (5)

  1. Proportion of participants with treatment-emergent adverse events (Phase I)

    Proportion of participants with Adverse Events, as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0 in Phase Ib

    Measured: From initiation of study treatment until 30 days post-treatment discontinuation

  2. Overall Response Rate (ORR) (Phase Ib)

    The ORR is defined as the best overall response recorded from the start of the treatment until disease progression or recurrence assessed over a 1-year period from the start of treatment using RECIST version 1.1 criteria. The percentages of patients with a best overall response rate of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be determined.

    Measured: Up to 12 months

  3. Mean Disease Control Rate (DCR) (Phase Ib)

    DCR will be defined as the percentage of patients who have achieved CR, PR, or SD (based on RECIST 1.1 criteria) for at least 12 weeks. The mean DCR and the standard deviation of DCR will be summarized.

    Measured: Up to 12 months

  4. Median Progression Free Survival (PFS) (Phase Ib)

    PFS will be calculated as 1+ the number of days from the first dose of study drugs to documented radiographic progression or death due to any cause. For patients who continue treatment post-progression, the date of radiographic progression will be used for PFS analysis. The Kaplan-Meier analysis will be used to calculate the median PFS with 95% confidence interval.

    Measured: Up to 12 months

  5. Overall survival (OS) (Phase Ib)

    OS will be calculated as 1+ the number of days from the first dose of study drugs to death due to any cause. The Kaplan-Meier analysis will be used to calculate the median PFS with 95% confidence interval.

    Measured: Up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jun 2022
  2. Study start10 Aug 2022
  3. Primary completion30 Nov 2023
  4. Study completion31 May 2024

Why it stopped: slow accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05435846
Sponsor's protocol ID
22653
Other IDs
NCI-2022-04800
Status last verified
Jun 2024
First submitted
22 Jun 2022
Last updated
11 Jun 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Brown T, Lara MS, Jiang F, Garon EB, Goldman JW, Riess JW, Blakely CM. Brief Report: Combination Capmatinib and Trametinib in Metastatic MET-Driven NSCLC. JTO Clin Res Rep. 2026 Aug 31;7(11):101072. doi: 10.1016/j.jtocrr.2026.101072. eCollection 2026 Nov.

    PubMed 42898856

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Capmatinib and Trametinib in people with Metastatic Lung Non-Small Cell Carcinoma and Stage IV Lung Cancer, run by Collin Blakely at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 11 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: slow accrual). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of participants with reported dose limiting toxicity (DLT) (Phase I) (time frame: 1 cycle (each cycle is 28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05435846, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in