Clinical trial NCT04849273: A Study of TPX-0131, a Novel Oral ALK Tyrosine Kinase Inhibitor, in Patients With ALK+ Advanced or Metastatic NSCLC
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non Small Cell Lung Cancer
Non-Small Cell Lung Cancer
NSCLC
Advanced Solid Tumor
Metastatic Solid Tumor
ALK Gene Mutation
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
Lead sponsor: Turning Point Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2021-04-19
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of first cycle dose-limiting toxicities (DLTs) of TPX-0131
timeFrame: Within 28 days of the first TPX-0131 dose for each patient
measure: Define the Recommended Phase 2 Dose
timeFrame: Approximately 24 months
Secondary outcomes:
measure: Adverse events (AEs)
timeFrame: Approximately 34 months
Other outcomes:
Locations:
city: Orange
country: United States
facility: Local Institution - 2104
state: California
city: Aurora
country: United States
facility: Local Institution - 2105
state: Colorado
city: Boston
country: United States
facility: Local Institution - 2106
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 2108
state: Massachusetts
city: Hackensack
country: United States
facility: Local Institution - 2103
state: New Jersey
city: Nashville
country: United States
facility: Local Institution - 2107
state: Tennessee
city: Fairfax
country: United States
facility: Local Institution - 2102
state: Virginia
city: Blacktown
country: Australia
facility: Local Institution - 6102
state: New South Wales
city: Heidelberg
country: Australia
facility: Local Institution - 6103
state: Victoria
city: Melbourne
country: Australia
facility: Local Institution - 6104
state: Victoria
city: Nedlands
country: Australia
facility: Local Institution - 6101
state: Western Australia
city: Seoul
country: Korea, Republic of
facility: Local Institution - 6303
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Local Institution - 6301
city: Seoul
country: Korea, Republic of
facility: Local Institution - 6302
city: Seoul
country: Korea, Republic of
facility: Local Institution - 6304
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: