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

Sponsor
Turning Point Therapeutics, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04849273
Collaborator
(none)
210
15
1
60
14
0.2

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.

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

Study Type:
Interventional
Anticipated Enrollment :
210 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2 Study of TPX-0131, A Novel Oral ALK Tyrosine Kinase Inhibitor in Subjects With ALK+ Advanced or Metastatic NSCLC
Actual Study Start Date :
Aug 2, 2021
Anticipated Primary Completion Date :
Apr 1, 2025
Anticipated Study Completion Date :
Aug 1, 2026

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

  1. 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

  2. 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

  3. 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

  1. Duration of Response (DOR) [Approximately 44 months]

    Determine the DOR of TPX-0131

  2. Time to response (TTR) [Approximately 44 months]

    Determine the TTR of TPX-0131

  3. Clinical benefit rate (CBR) [Approximately 44 months]

    Determine the CBR of TPX-0131

  4. Intracranial tumor response [Approximately 44 months]

    Determine the intracranial tumor response in subjects with measurable brain metastases, as determined by BICR.

  5. Progression free survival (PFS) [Approximately 44 months]

    Determine the PFS of TPX-0131

  6. Overall survival (OS) [Approximately 44 months]

    Determine the efficacy and safety of TPX-0131

  7. Adverse events (AEs) [Approximately 44 months]

    Evaluate the overall safety profile of TPX-0131

  8. CNS Progression-Free Survival (CNS-PFS) [Approximately 44 months]

    Determine the CNS-PFS in patients with measurable brain metastases using Modified RECIST v1.1

  9. Cmax (maximum plasma concentration) of TPX-0131 [Up to 120 hours post-dose]

    Evaluate the maximum plasma concentration of TPX-0131

  10. AUC (area under plasma concentration time curve) of TPX-0131 [Up to 120 hours post-dose]

    Determine the AUC of TPX-0131

  11. 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.

  12. 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

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts 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.

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.
Responsible Party:
Turning Point Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT04849273
Other Study ID Numbers:
  • TPX-0131-01
First Posted:
Apr 19, 2021
Last Update Posted:
May 4, 2022
Last Verified:
May 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Turning Point Therapeutics, Inc.
Additional relevant MeSH terms:

Study Results

No Results Posted as of May 4, 2022