Phase 2 Study of Study of Tesevatinib in Subjects With NSCLC and Brain or Leptomeningeal Metastases

Study summary

A study to assess the activity of tesevatinib in subjects with non-small cell lung cancer (NSCLC) and activating epidermal growth factor receptor (EGFR) mutations who have disease progression with Brain Metastases (BM) or Leptomeningeal Metastases (LM) or who have either BM or LM at initial presentation (IP)

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Key things to know

Main goalTreatment

This describes the study’s primary purpose.

What is being studiedTesevatinib

The study team can explain what participation involves.

Who it may be forNon-small cell lung cancer (NSCLC) · EGFR

These are broad labels—not an eligibility decision.

Checked against the public recordLast updated Mar 16, 2022 · Source: ClinicalTrials.gov

Is enrollment open?Completed

Ask the study team to confirm whether enrollment is open.

What kind of study?Phase 2

Interventional

Where is it offered?7 U.S. locations

Locations may change over time.

Who runs it?Kadmon Corporation, LLC

Study sponsor

Study overview

What this study is about

Purpose: Treatment
Study type: Interventional
Phase: Phase 2
Sponsor: Kadmon Corporation, LLC
Interventions being studied: Drug: Tesevatinib

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How this study is categorized

These labels come from structured fields and exact terms in the public record.

Cancer type

Non-small cell lung cancer (NSCLC)→

Biomarkers

EGFR→

Study topics

Brain metastases→

Public criteria

Who may be able to participate

The sponsor separates these requirements into two groups. You do not need to interpret them alone—use them to guide a conversation with the study team.

Requirements people may need to meetInclusion criteria

Cohort A
History of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation or an EGFR activating mutation that has had a clinical response to erlotinib, afatinib, or gefitinib in the patient being enrolled
Occurrence or progression of BM while receiving first-line therapy (either erlotinib, afatinib, or gefitinib) for at least 14 days. Patients may have received osimertinib (or other agents inhibiting the T790M EGFR mutation) as second line therapy. If BM progression occurs after osimertinib, patient will be eligible.
At least one measurable BM by RECIST 1.1 criteria (≥ 10 mm in longest diameter). Target lesions must not have received stereotactic radiotherapy (SRS). If a subject had prior whole brain radiotherapy (WBRT), progression in any measurable BM lesion must have occurred at least 3 months after the end of WBRT. Subjects with asymptomatic brain metastases may have been enrolled without prior radiation therapy to the brain. Subjects with minimally symptomatic brain metastases may have been enrolled without prior radiation therapy to the brain if they do not require immediate surgical or radiation therapy in the opinion of the treating investigator and in the opinion of a radiation therapy or neurosurgical consultant
Subjects in Cohort A may have had asymptomatic LM detected by MRI. (Subjects with symptoms or signs attributed to LM were enrolled in Cohort B whether or not they have brain metastases)
No clinically significant progression outside of the CNS on most recent EGFR inhibitor therapy
ECOG Score ≤ 2
No history of another malignancy in the 5 years prior to study entry, except treated non-melanoma skin cancer or superficial bladder cancer or carcinoma in situ of the cervix or Stage 1 or 2 cancers of other sites that have been treated surgically and have not recurred
Adequate organ and bone marrow functions
Serum potassium and magnesium levels above the lower limit of normal
No coexisting medical problems of sufficient severity to limit compliance with the study
Willing and able to sign written informed consent and able to comply with the study protocol for the duration of the study
Women of childbearing potential (i.e., menstruating women) must have had a negative urine pregnancy test (positive urine tests confirmed by serum test)

Reasons someone may not be able to joinExclusion criteria

First day of dosing with tesevatinib less than 2 weeks from the last treatment of cytotoxic chemotherapy, biological therapy, or immunotherapy, and less than 6 weeks for nitrosoureas and mitomycin C. Surgical procedures must have been performed at least 2 weeks prior to the start of study treatment. Subjects must have recovered from the reversible effects of prior lung cancer treatments, including surgery and radiation therapy (excluding alopecia).
First day of dosing with tesevatinib less than 4 weeks from the last radiotherapy of the brain or spinal cord/cauda equina
First day of dosing with tesevatinib less than 2 weeks from treatment with another investigational agent
Treatment with erlotinib must have been discontinued at least 3 days prior to first dose of tesevatinib and treatment with afatinib or other tyrosine kinase inhibitor must have been discontinued at least 3 days prior to first dose of tesevatinib
Any concurrent therapy for BM other than the specified treatment in this study
Taking any medication known to moderately or severely inhibit the CYP3A4 isozyme or any drugs that are CYP3A4 inducers (including anti-epileptic agents such as phenytoin). A stable regimen (≥ 4 weeks) of antidepressants of the selective serotonin uptake inhibitor (SSRI) class was allowed (common SSRIs include escitalopram oxalate, citalopram, fluvoxamine, paroxetine, sertraline, and fluoxetine)
Taking any drugs associated with torsades de pointes or known to moderately or severely prolong the QTc(F) interval
Evidence of active heart disease such as myocardial infarction within the 3 months prior to study entry; symptomatic coronary insufficiency congestive heart failure; moderate or severe pulmonary dysfunction
History of torsades de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (\< 50 bpm), heart block (excluding first degree block, being PR interval only), or congenital long QT syndrome. Subjects with a history of atrial arrhythmias were discussed with the medical monitor
Had an active infectious process
Female subject pregnant or lactating
Known contraindication to MRI, such as cardiac pacemaker, shrapnel, or ocular foreign body
Marked prolongation of QTc(F) interval at screening or baseline (QTc\[F\] interval \> 470 msec) using the Fridericia method of correction for heart rate
Gastrointestinal (GI) condition interfering with drug absorption
Non-malignant neurological disease that would interfere with evaluation of symptoms or signs of brain metastases Cohort B Inclusion Criteria:
History of NSCLC with EGFR mutation (either exon 19 deletion or L858R mutation) or, if previously treated, history of an activating EGFR mutation that had a clinical response to erlotinib, afatinib, or gefitinib in the subject being enrolled).
Presentation with LM at initial presentation with no prior systemic treatment, or occurrence or progression of LM while receiving first-line therapy (either erlotinib, afatinib, or gefitinib) for at least 14 days. Patients may have received osimertinib (or other agents inhibiting the T790M EGFR mutation) as second line therapy. If LM progression occurred after osimertinib, subjects were eligible.
Presence of at least one CTCAE 4.03 symptom/sign of at least Grade 1 attributed by the investigator to LM
Diagnosis of LM by: 1. Cytological evidence in cerebrospinal fluid (CSF) sample of LM due to NSCLC, and/or 2. Findings on gadolinium-enhanced MRI
No clinically significant progression outside of the CNS on most recent EGFR inhibitor therapy
Concomitant brain metastases and brain metastases previously treated with radiation therapy were allowed. (Subjects with symptoms or signs attributed to LM will be enrolled in Cohort B whether or not they have brain metastases)
ECOG Score ≤ 2
No history of another malignancy in the 5 years prior to study entry, except treated non-melanoma skin cancer or superficial bladder cancer or carcinoma in situ of the cervix or Stage 1 or 2 cancers of other sites that have been treated surgically and had not recurred
Adequate organ and bone marrow functions
Serum potassium and magnesium levels above the lower limit of normal (LLN)
No coexisting medical problems of sufficient severity to limit compliance with the study
Willing and able to sign written informed consent and able to comply with the study protocol for the duration of the study
Women of childbearing potential (i.e., menstruating women) must have had a negative urine pregnancy test (positive urine tests confirmed by serum test)

Important: This is the sponsor’s public criteria, not a determination of eligibility. The study team must review your individual situation.

Study sites

U.S. locations

Beverly Hills Cancer CenterBeverly Hills, California
USC Norris Oncology/Hematology Newport BeachNewport Beach, California
John Wayne Cancer InstituteSanta Monica, California
University of Colorado Cancer CenterAurora, Colorado
Georgetown University Medical CenterWashington D.C., District of Columbia
Sarah Cannon Research InstituteNashville, Tennessee
UT M.D. Anderson Cancer CenterHouston, Texas

Source and freshness
Processed from ClinicalTrials.gov. Last public update: Mar 16, 2022. Always confirm current availability with the study team.

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