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

NCT02616393 | Completed Phase 2 Results DMC

• 1 other identifier: KD019-206
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 7

Brief 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)

Conditions

Non-Small Cell Lung Cancer; Leptomeningeal Metastases; Brain Metastases

Outcome Measures

Primary Outcomes (2)

• Best Overall Response Rate (ORR) of Subjects With BM

  The best overall response rates (ORRs) of subjects who had brain tumors and exhibited either a complete response (CR) or a partial responder (PR) to therapy divided by the total number of subjects treated with tesevatinib 300 mg PO QD. Response rates are in accordance with RECIST Version 1.1 criteria. Since such brain metastases (BM) tumors can either affect the central nervous system (CNS) or not affect the CNS (non-CNS), they were categorized into CNS and non-CNS subsets. Because leptomeningeal metastases (LM) only are considered cancer cell migration from the breast, lung, or some other part of the body to the cerebrospinal fluid (CSF), analysis of CNS are not appropriate, so Cohort B is excluded.

  Until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first

• Best ORR of Subjects With LM

  The best overall response rates (ORRs) of subjects who had leptomeningeal tumors and exhibited either a complete response (CR) or a partial responder (PR) to therapy divided by the total number of subjects treated with tesevatinib 300 mg PO QD. Response rates are in accordance with RECIST Version 1.1 criteria. Since leptomeningeal metastases (LM) are only considered cancer cell migration from the breast, lung, or some other part of the body to the cerebrospinal fluid (CSF), analysis of CNS are not appropriate, so Cohorts A and C are excluded.

  Until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first

Secondary Outcomes (9)

• Median Progression-free Survival (PFS)

  Until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first

• Probability of PFS at 12 Weeks and 24 Weeks--Cohort A (BM Only) and Cohort B (LM Only)

  24 weeks (6 months)

• Probability of PFS at 24 Weeks--Cohort C (BM-IP Only)

  24 weeks (6 months)

• Probability of OS at 12 Weeks and at 24 Weeks--Cohort A (BM Only) and Cohort B (LM Only)

  24 weeks (6 months)

• Median Time to Progression (TTP)--Cohort A (BM), Cohort B (LM), Cohort C (BM-IP)

  Until disease progression, death, unacceptable toxicity, or up to 2 years, whichever occurred first

Study Arms (3)

Cohort A: Brain Metastases (BM)

EXPERIMENTAL

Tesevatinib 300 mg orally (PO) once daily (QD) administered to subjects with NSCLC who had progressed with brain metastases (BM)

Drug: Tesevatinib

Cohort B: Leptomeningeal Metastases (LM)

EXPERIMENTAL

Tesevatinib 300 mg PO QD administered to subjects with NSCLC who had progressed with leptomeningeal metastases (LM)

Drug: Tesevatinib

Cohort C: Brain Metastases at Initial Presentation (BM-IP)

EXPERIMENTAL

Tesevatinib 300 mg PO QD administered NSCLC who presented initially with BM at initial presentation

Drug: Tesevatinib

Interventions

Tesevatinib DRUG

Also known as: KD019, XL647

Cohort A: Brain Metastases (BM); Cohort B: Leptomeningeal Metastases (LM); Cohort C: Brain Metastases at Initial Presentation (BM-IP)

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Kadmon Corporation, LLC: lead

Study Sites (7)

Beverly Hills Cancer Center

Beverly Hills, California, 90211, United States

Location

USC Norris Oncology/Hematology Newport Beach

Newport Beach, California, 92663, United States

Location

John Wayne Cancer Institute

Santa Monica, California, 90404, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

UT M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Meningeal Carcinomatosis; Brain Neoplasms

Interventions

XL647

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Brain Diseases; Central Nervous System Diseases

Results Point of Contact

• Title: Miranda Ross
• Organization: Kadmon Corporation

Miranda.Ross@kadmon.com

724-778-6170

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: November 20, 2015
• First Posted: November 26, 2015
• Study Start: November 1, 2015
• Primary Completion: April 3, 2018
• Study Completion: April 3, 2018
• Last Updated: March 16, 2022
• Results First Posted: November 23, 2021

Record last verified: 2022-03

Locations

US (7)