Advanced Solid Tumor, ALK Gene Mutation, Metastatic Solid Tumor, Non Small Cell Lung Cancer, Non-Small Cell Lung Cancer, NSCLC
Conditions
Keywords
Non Small Cell Lung Cancer, Non-Small Cell Lung Cancer, NSCLC, Advanced Non-Small Cell Lung Cancer, Advanced/metastatic disease, Lung cancer, Metastatic solid tumor, Advanced solid tumor, ALK gene fusion, ALK inhibitor, TPX-0131, ALK TKI, ALK Tyrosine Kinase Inhibitor
Brief summary
A phase 1, first-in-human, open-label study to evaluate the safety, tolerability, PK, and efficacy of the novel ALK inhibitor TPX-0131 in pretreated subjects with ALK+ advanced or metastatic non-small cell lung cancer (NSCLC).
Detailed description
Phase 1 Dose Escalation: To evaluate the overall safety profile, efficacy of TPX-0131 in pretreated subjects with ALK+ advanced or metastatic NSCLC.
Interventions
DRUGTPX-0131
Oral TPX-0131 tablets
Sponsors
Turning Point Therapeutics, 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
* Age ≥ 18 (or as required by local regulation). * Histological or cytological confirmation of advanced/metastatic ALK+ NSCLC. * Pretreated with up to three prior lines of an ALK TKI treatment, including at least one prior line of a second or third-generation ALK TKI (alectinib, brigatinib, ensartinib, or lorlatinib) in Phase 1. * ECOG performance status ≤ 1. * Existence of measurable or evaluable disease (according to Response evaluation criteria in solid tumors \[RECIST v1.1\] criteria). * Subjects with asymptomatic CNS metastases and/or asymptomatic leptomeningeal carcinomatosis are eligible. * Adequate organ function.
Exclusion criteria
* Major surgery within four weeks of the start of TPX-0131 treatment. * Clinically significant cardiovascular disease * Any of the following cardiac criteria: * Mean resting corrected QT interval (QTc) \> 470 msec obtained from three ECGs and any factors that increase the risk of QTc prolongation or arrhythmic events * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG * Known clinically significant active infections not controlled with systemic treatment (bacterial, fungal, viral including HIV positivity). * Gastrointestinal disease or other malabsorption syndromes that would impact drug absorption. * Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers. * Subjects with current or anticipated need for drugs that are sensitive CYP2C9 substrates with narrow therapeutic indices.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of first cycle dose-limiting toxicities (DLTs) of TPX-0131 | Within 28 days of the first TPX-0131 dose for each patient | Evaluate the safety and tolerability of TPX-0131 |
| Define the Recommended Phase 2 Dose | Approximately 24 months | Determine the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of TPX-0131 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events (AEs) | Approximately 34 months | Evaluate the overall safety profile of TPX-0131 |
Countries
Australia, South Korea, United States
Outcome results
None listed