A Study of TPX-0131, a Novel Oral ALK Tyrosine Kinase Inhibitor, in Patients With ALK+ Advanced or Metastatic NSCLC

Study Overview
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Brief Summary
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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
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Phase 1 Dose Escalation: To evaluate the overall safety profile, efficacy of TPX-0131 in pretreated subjects with ALK+ advanced or metastatic NSCLC.

Official Title
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A Phase 1/2 Study of TPX-0131, A Novel Oral ALK Tyrosine Kinase Inhibitor in Subjects With ALK+ Advanced or Metastatic NSCLC

Conditions
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Non Small Cell Lung Cancer, Non-Small Cell Lung Cancer, NSCLC, Advanced Solid Tumor, Metastatic Solid Tumor, ALK Gene Mutation

Intervention / Treatment
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* Drug: TPX-0131


Participation Criteria
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Eligibility Criteria
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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.

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: TPX-0131<br>The Phase 1 part of the study will determine the safety, tolerability, PK, MTD, and RP2D of TPX-0131. | Drug: TPX-0131<br>* Oral TPX-0131 tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of first cycle dose-limiting toxicities (DLTs) of TPX-0131 | Evaluate the safety and tolerability of TPX-0131 | Within 28 days of the first TPX-0131 dose for each patient | 
| Define the Recommended Phase 2 Dose | Determine the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of TPX-0131 | Approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (AEs) | Evaluate the overall safety profile of TPX-0131 | Approximately 34 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced/metastatic disease, Non Small Cell Lung Cancer, Non-Small Cell Lung Cancer, NSCLC, Advanced Non-Small Cell Lung Cancer, Lung cancer, Metastatic solid tumor, Advanced solid tumor, ALK gene fusion, ALK inhibitor, TPX-0131, ALK TKI, ALK Tyrosine Kinase Inhibitor