Non-small Cell Lung Cancer, Non-squamous NSCLC, NSCLC
Conditions
Keywords
TH-4000, low-oxygen conditions, hypoxia, non-small cell lung cancer, NSCLC, squamous cell carcinoma, Tarloxotinib
Brief summary
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
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.
Interventions
TH-4000 (Tarloxotinib) is a hypoxia-activated prodrug
Sponsors
Rain Oncology Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with response rate as evaluated by RECIST criteria | Approximately 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Cycle 1 Day 1 predose and up to 24 hours post dose | Time to peak plasma concentration (Tmax), maximum plasma concentration (Cmax), area under concentration-time curve (AUC) |
| 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 | — |
| Incidence of adverse events (AEs) | Up to 30 days after last dose | — |
Other
| Measure | Time frame |
|---|---|
| Hypoxic volume as measured by Positron Emission Tomography (PET) hypoxia imaging | Baseline |
Countries
Australia, United States
Outcome results
None listed