A Study of TPX-0131, a Novel Oral ALK Tyrosine Kinase Inhibitor, in Patients With ALK+ Advanced or Metastatic NSCLC
Study Details
Study Description
Brief Summary
A phase 1/2, 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). The study consists of two portions: 1) Phase 1 dose escalation, and 2) Phase 2 efficacy evaluation.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1/Phase 2 |
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.
Phase 2 Efficacy Evaluation: To determine the safety and anti-tumor efficacy of TPX-0131 in defined cohorts of subjects with advanced or metastatic ALK+ NSCLC.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: TPX-0131 The Phase 1 part of the study will determine the safety, tolerability, PK, MTD, and RP2D of TPX-0131. The Phase 2 part of the study will determine the safety, tolerability, PK and preliminary efficacy of TPX-0131 in specific cohorts. |
Drug: TPX-0131
Oral TPX-0131 tablets
|
Outcome Measures
Primary Outcome Measures
- 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 22 months]
Determine the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of TPX-0131
- Define the objective response rate (ORR) [Approximately 44 months]
Determine the preliminary efficacy by the ORR in defined cohorts with ALK+ advanced or metastatic NSCLC
Secondary Outcome Measures
- Duration of Response (DOR) [Approximately 44 months]
Determine the DOR of TPX-0131
- Time to response (TTR) [Approximately 44 months]
Determine the TTR of TPX-0131
- Clinical benefit rate (CBR) [Approximately 44 months]
Determine the CBR of TPX-0131
- Intracranial tumor response [Approximately 44 months]
Determine the intracranial tumor response in subjects with measurable brain metastases, as determined by BICR.
- Progression free survival (PFS) [Approximately 44 months]
Determine the PFS of TPX-0131
- Overall survival (OS) [Approximately 44 months]
Determine the efficacy and safety of TPX-0131
- Adverse events (AEs) [Approximately 44 months]
Evaluate the overall safety profile of TPX-0131
- CNS Progression-Free Survival (CNS-PFS) [Approximately 44 months]
Determine the CNS-PFS in patients with measurable brain metastases using Modified RECIST v1.1
- Cmax (maximum plasma concentration) of TPX-0131 [Up to 120 hours post-dose]
Evaluate the maximum plasma concentration of TPX-0131
- AUC (area under plasma concentration time curve) of TPX-0131 [Up to 120 hours post-dose]
Determine the AUC of TPX-0131
- Patient-reported quality of life - Core Quality of Life Questionnaire [Approximately 44 months]
Estimate the effect of TPX-0131 on patient-reported outcomes using the European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire to assess subject's ability to complete 30 daily activities. The scale, from 1 to 4 (1 = not difficult to 4 = very difficult), indicates the level of difficulty to complete a task.
- Patient-reported quality of life - Lung Cancer Quality of Life Questionnaire [Approximately 44 months]
Estimate the effect of TPX-0131 on patient-reported outcomes, using the Lung Cancer Quality of Life Questionnaire asks questions related to 13 specific lung cancer symptoms. The scale, from 1 to 4 (1 = not often to 4 = very often), indicates the frequency of symptoms experienced in a given week.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥ 18 (or as required by local regulation).
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Histological or cytological confirmation of advanced/metastatic ALK+ NSCLC.
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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.
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ECOG performance status ≤ 1.
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Existence of measurable or evaluable disease (according to Response evaluation criteria in solid tumors [RECIST v1.1] criteria).
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Subjects with asymptomatic CNS metastases and/or asymptomatic leptomeningeal carcinomatosis are eligible.
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Adequate organ function.
Exclusion Criteria:
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Major surgery within four weeks of the start of TPX-0131 treatment.
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Clinically significant cardiovascular disease
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Any of the following cardiac criteria:
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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
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Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG
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Known clinically significant active infections not controlled with systemic treatment (bacterial, fungal, viral including HIV positivity).
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Gastrointestinal disease or other malabsorption syndromes that would impact drug absorption.
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Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
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Subjects with current or anticipated need for drugs that are sensitive CYP2C9 substrates with narrow therapeutic indices.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | UC Irvine Health - Chao Family Comprehensive Cancer Center | Orange | California | United States | 92868 |
2 | University of Colorado, Anschutz Medical Campus | Aurora | Colorado | United States | 80045 |
3 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
4 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
5 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
6 | Sarah Cannon Research Institute at Tennessee Oncology | Nashville | Tennessee | United States | 37203 |
7 | Virginia Cancer Specialists | Fairfax | Virginia | United States | 22031 |
8 | Blacktown Cancer and Hematology Centre | Blacktown | New South Wales | Australia | 2148 |
9 | Austin Health | Heidelberg | Victoria | Australia | 3084 |
10 | Peter MacCallum Cancer Centre | Melbourne | Victoria | Australia | 3000 |
11 | Linear Clinical Research | Nedlands | Western Australia | Australia | 6009 |
12 | Seoul National University Hospital | Seoul | Korea, Republic of | 03080 | |
13 | Yonsei Cancer Center, Severance Hospital | Seoul | Korea, Republic of | 03722 | |
14 | Asan Medical Center | Seoul | Korea, Republic of | 05505 | |
15 | Samsung Medical Center | Seoul | Korea, Republic of | 06351 |
Sponsors and Collaborators
- Turning Point Therapeutics, Inc.
Investigators
- Study Director: Turning Point Therapeutics, MD, Turning Point Therapeutics
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TPX-0131-01