Study for Treatment With TH-4000 (Tarloxotinib) in Epidermal Growth Factor Receptor (EGFR) Mutant, T790M-negative Non-small Cell Lung Cancer (NSCLC) Patients

Study Overview
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Brief Summary
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This phase 2 study is designed to evaluate the safety and activity of TH-4000 a hypoxia-activated prodrug, in patients with EGFR-Mutant, T790M-Negative, Advanced NSCLC.

Detailed Description
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A single arm open label multi-center Phase 2 study in which the pharmacokinetics, safety, tolerability and efficacy of TH-4000 will be assessed in patients with EGFR mutant, T790M negative advanced NSCLC. Patients must have demonstrated progression during EGFR TKI therapy. Hypoxia PET scans will be obtained in select centers to analyze potential predictors of tumor response.

Official Title
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A Phase 2 Study of TH-4000 (Tarloxotinib) in Patients With EGFR-Mutant, T790M-Negative, Advanced Non-Small Cell Lung Cancer Progressing on an EGFR Tyrosine Kinase Inhibitor

Conditions
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Non-small Cell Lung Cancer, NSCLC, Non-squamous NSCLC

Intervention / Treatment
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* Drug: TH-4000 (Tarloxotinib)


Participation Criteria
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Eligibility Criteria
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Key Eligibility Criteria: Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Confirmed recurrent Stage IV NSCLC which progressed while on treatment with EGFR TKI Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) Documented evidence of an EGFR mutation known to be associated with an EGFR TKI sensitivity No T790M mutation or small cell transformation including an assessment from tumor biopsy obtained while on or subsequent to the most recent EGFR TKI therapy Acceptable laboratory results as indicated by protocol Acceptable cardiac function as indicated by protocol Key Exclusion Criteria: Receiving medication that prolongs QT interval, with a risk of causing Torsades de Pointes (TdP) unless ECG meets inclusion criteria while on a stable dose of the medication Family history of long corrected QT interval (QTc) syndrome Symptomatic central nervous system (CNS) lesions Radiation therapy within 2 weeks prior to the first dose of study medication Major surgery within 4 weeks or minor surgery within 2 weeks prior to the first dose of study medication Concurrent active malignancy requiring systemic treatment Any other serious uncontrolled medical disorders or psychological conditions that may interfere with study conduct including but not limited to: clinically significant active infection (e.g., tuberculosis, viral hepatitis, human immunodeficiency virus [HIV]), recent (within 6 months) myocardial infarction or unstable angina, congestive heart failure, poorly-controlled hypertension or diabetes, concurrent active malignancy, or psychiatric condition that may interfere with the patient's ability to follow study procedures Pregnant or breast-feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TH-4000 (Tarloxotinib)<br>TH-4000 (Tarloxotinib), 150 mg/m2 will be administered by IV infusion on Days 1, 8, 15, and 22 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity | Drug: TH-4000 (Tarloxotinib)<br>* TH-4000 (Tarloxotinib) is a hypoxia-activated prodrug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with response rate as evaluated by RECIST criteria |  | Approximately 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) |  | Up to 30 days after last dose | 
| Type of adverse events (AEs) |  | Up to 30 days after last dose | 
| Severity of adverse events (AEs) |  | Up to 30 days after last dose | 
| Duration of response (DOR) calculated for all patients achieving an objective response |  | Approximately 12 months | 
| Progression-free survival (PFS) |  | Approximately 12 months | 
| Overall Survival (OS) |  | Approximately 12 months | 
| Time to peak plasma concentration (Tmax) | Time to peak plasma concentration (Tmax), maximum plasma concentration (Cmax), area under concentration-time curve (AUC) | Cycle 1 Day 1 predose and up to 24 hours post dose | 
| Maximum plasma concentration (Cmax) |  | Cycle 1 Day 1 predose and up to 24 hours post dose | 
| Area under concentration-time curve (AUC) |  | Cycle 1 Day 1 predose and up to 24 hours post dose | 
| QTc Interval |  | Screening, Cycle 1 Day 1, 8, 15 & 22, Day 1 of subsequent cycles | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TH-4000, low-oxygen conditions, hypoxia, non-small cell lung cancer, NSCLC, squamous cell carcinoma, Tarloxotinib