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

Phase 1

Terminated

• Conditions: Non Small Cell Lung Cancer; Non-Small Cell Lung Cancer; NSCLC; Advanced Solid Tumor; Metastatic Solid Tumor; ALK Gene Mutation
• Interventions: Drug: TPX-0131

• Registration Number: NCT04849273
• Lead Sponsor: Turning Point Therapeutics, Inc.

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.

Study Timeline

• Study First Submitted: 2021-04-12
• Study First Submitted QC: 2021-04-16
• Study First Posted: 2021-04-19
• Study Start: 2021-07-28
• Primary Completion: 2023-04-18
• Study Completion: 2023-04-18
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-24
• Last Update Posted: 2023-05-26

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 11

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TPX-0131	TPX-0131	The Phase 1 part of the study will determine the safety, tolerability, PK, MTD, and RP2D of TPX-0131.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Adverse events (AEs)	Approximately 34 months	Evaluate the overall safety profile of TPX-0131

Trial Locations

Locations (15)

Local Institution - 2103; 🇺🇸 Hackensack, New Jersey, United States

Local Institution - 2102; 🇺🇸 Fairfax, Virginia, United States

Local Institution - 6304; 🇰🇷 Seoul, Korea, Republic of

Local Institution - 6101; 🇦🇺 Nedlands, Western Australia, Australia

Local Institution - 6302; 🇰🇷 Seoul, Korea, Republic of

Local Institution - 6301; 🇰🇷 Seoul, Korea, Republic of

Local Institution - 2104; 🇺🇸 Orange, California, United States

Local Institution - 6102; 🇦🇺 Blacktown, New South Wales, Australia

Local Institution - 6103; 🇦🇺 Heidelberg, Victoria, Australia

Local Institution - 6104; 🇦🇺 Melbourne, Victoria, Australia

Local Institution - 6303; 🇰🇷 Seoul, Seoul-teukbyeolsi, Korea, Republic of

Local Institution - 2105; 🇺🇸 Aurora, Colorado, United States

Local Institution - 2108; 🇺🇸 Boston, Massachusetts, United States

Local Institution - 2106; 🇺🇸 Boston, Massachusetts, United States

Local Institution - 2107; 🇺🇸 Nashville, Tennessee, United States