- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04161391
Study of TPX-0046, A RET/SRC Inhibitor in Adult Subjects With Advanced Solid Tumors Harboring RET Fusions or Mutations
A Phase 1/2 Study of TPX-0046, A Novel Oral RET/SRC Inhibitor in Adult Subjects With Advanced/Metastatic Solid Tumors Harboring Oncogenic RET Fusions or Mutations
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Phase 1 Dose Escalation and Dose Expansion: To evaluate the overall safety profile, characterize the PK profiles and assess the preliminary efficacy of TPX-0046 in adults subjects with advanced solid tumors harboring oncogenic RET fusions or mutations.
Food Effect Sub-Study: To determine the effect of food on PK of TPX-0046 in adult subjects with advanced or metastatic solid tumors harboring oncogenic RET fusions or mutations.
Phase 2 Efficacy Evaluation: To determine the overall safety and anti-tumor efficacy of TPX-0046 in defined cohorts of subjects with advanced/metastatic solid tumors harboring oncogenic RET fusions or mutations.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Seoul, Korea, Republic of, 120-752
- Local Institution - 6320
-
-
-
-
California
-
La Jolla, California, United States, 92093-0698
- Local Institution - 2129
-
Orange, California, United States, 92868
- Local Institution - 2128
-
-
Colorado
-
Aurora, Colorado, United States, 80045
- Local Institution - 2122
-
Denver, Colorado, United States, 80218
- SCRI - HealthOne Denver
-
-
District of Columbia
-
Washington, District of Columbia, United States, 20007
- Local Institution - 2126
-
-
Florida
-
Jacksonville, Florida, United States, 32224
- Mayo Clinic - Jacksonville
-
Tampa, Florida, United States, 33612-9416
- Local Institution - 2130
-
-
Georgia
-
Atlanta, Georgia, United States, 30322
- Local Institution - 2127
-
-
Illinois
-
Chicago, Illinois, United States, 60637
- University of Chicago Medicine
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital
-
-
Michigan
-
Ann Arbor, Michigan, United States, 48109-5000
- Local Institution - 2124
-
Detroit, Michigan, United States, 48201
- Local Institution - 2131
-
-
Minnesota
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic - Rochester
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic - Arizona
-
-
New York
-
New York, New York, United States, 10021
- Memorial Sloan Kettering Cancer Center
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19111
- Fox Chase Cancer Center
-
-
Texas
-
Houston, Texas, United States, 77030
- Baylor College of Medicine - Baylor Heart Clinic
-
Houston, Texas, United States, 77030-3721
- Local Institution - 2120
-
-
Virginia
-
Fairfax, Virginia, United States, 22031
- Local Institution - 2135
-
-
Washington
-
Seattle, Washington, United States, 98195
- Local Institution - 2132
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age ≥ 18 (or age ≥ 20 as required by local regulation).
- Histological or cytological confirmation of advanced/metastatic solid tumors harboring oncogenic RET fusions or mutations, who either have disease progression on, or are intolerant to standard therapy; OR are ineligible for standard therapy or for whom no standard therapy exists; OR are unlikely to tolerate or derive clinical benefit from standard therapy in the opinion of the Investigator OR have declined standard therapy.
- 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 primary CNS tumors or brain metastases are eligible for the study if they meet protocol specified criteria.
- Adequate organ function.
- Life expectancy ≥ 12 weeks.
Exclusion Criteria:
- Locally advanced solid tumor that is a candidate for curative treatment through radical surgery and/or radiotherapy, or chemotherapy.
- Presence or history of any other primary malignancy within 3 years other than a history of adequately treated basal or squamous cell carcinoma of the skin, or any adequately treated in situ carcinoma.
- Major surgery within four weeks of the start of therapy.
- Clinically significant cardiovascular disease (either active or within six months before enrollment): myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Classification Class ≥ II), cerebrovascular accident or transient ischemic attack, symptomatic bradycardia, requirement for anti-arrhythmic medication. Ongoing cardiac dysrhythmias of CTCAE version 5.0 grade ≥ 2.
Any of the following cardiac criteria:
- Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) > 470 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value
- Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250 msec)
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
- Known clinically significant active infections not controlled with systemic treatment (bacterial, fungal, viral including HIV positivity).
- Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) 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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: TPX-0046
The Phase 1 part of the study will determine the safety, tolerability, PK, MTD, and RP2D of TPX-0046. The food-effect sub-study determines the effect of food on a dose of TPX-0046 at the RP2D dose level. The Phase 2 part of the study will determine the safety, tolerability, PK, and preliminary efficacy in specific cohorts. Phase 2 Cohorts:
|
Oral TPX-0046 capsules
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of first cycle dose-limiting toxicities (DLTs) of TPX-0046
Time Frame: Within 28 days of the first TPX-0046 dose for each patient
|
Evaluate the safety and tolerability of TPX-0046
|
Within 28 days of the first TPX-0046 dose for each patient
|
Define the Recommended Phase 2 Dose
Time Frame: Approximately 24 months
|
Determine the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of TPX-0046
|
Approximately 24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse events (AEs)
Time Frame: Approximately 48 months
|
Evaluate the overall safety profile of TPX-0046
|
Approximately 48 months
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- NSCLC
- lung cancer
- Non-small cell lung cancer
- Advanced Solid Tumors
- lung adenocarcinoma
- Metastatic solid tumor
- Non small cell lung cancer
- Medullary Thyroid Cancer
- Thyroid cancer
- MTC
- RET gene mutation
- RET gene alteration
- Advanced non small cell lung cancer
- Advanced/metastatic disease
- RET gene fusion
- RET inhibitor
- SRC
- TPX-0046
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Lung Diseases
- Neoplasms by Site
- Endocrine System Diseases
- Endocrine Gland Neoplasms
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Thyroid Diseases
- Head and Neck Neoplasms
- Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Thyroid Neoplasms
Other Study ID Numbers
- CA129-1036 (Other Identifier: Bristol-Myers Squibb Protocol ID)
- TPX-0046-01 (Other Identifier: Turning Point Therapeutics Protocol ID)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Non Small Cell Lung Cancer
-
WindMIL TherapeuticsBristol-Myers SquibbTerminatedNSCLC | Lung Cancer | Lung Cancer Metastatic | Lung Cancer, Non-small Cell | Non Small Cell Lung Cancer | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Metastatic | Non Small Cell Lung Cancer MetastaticUnited States
-
University of California, San FranciscoAstraZenecaActive, not recruitingStage IIIA Non-Small Cell Lung Cancer | Stage I Non-Small Cell Lung Cancer | Stage IA Non-Small Cell Lung Cancer | Stage IB Non-Small Cell Lung Cancer | Stage II Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Cancer | Stage IIB Non-Small Cell Lung CancerUnited States
-
University of Wisconsin, MadisonNational Cancer Institute (NCI)CompletedStage IIIA Non-small Cell Lung Cancer | Stage IIIB Non-small Cell Lung Cancer | Extensive Stage Small Cell Lung Cancer | Recurrent Small Cell Lung Cancer | Recurrent Non-small Cell Lung Cancer | Stage IV Non-small Cell Lung Cancer | Healthy, no Evidence of Disease | Limited Stage Small Cell Lung... and other conditionsUnited States
-
AIO-Studien-gGmbHBristol-Myers Squibb; Eli Lilly and Company; Merck Sharp & Dohme LLC; Pfizer; Gilead... and other collaboratorsRecruitingSmall-cell Lung Cancer | Non-small Cell Lung Cancer Metastatic | Non-small Cell Lung Cancer Stage I | Metastatic Non-small Cell Lung Cancer (NSCLC) | Non Small Cell Lung Cancer Stage III | Non-small Cell Lung Cancer Stage IIGermany
-
Alexander ChiNot yet recruitingNon-small Cell Lung Cancer Stage III | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Stage I | Non-small Cell Carcinoma | Non-small Cell Lung Cancer Stage IIChina
-
National Cancer Institute (NCI)TerminatedStage IIIA Non-small Cell Lung Cancer | Stage IA Non-small Cell Lung Cancer | Stage IB Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB Non-small Cell Lung CancerUnited States
-
National Cancer Institute (NCI)Not yet recruitingStage IIIA Non-small Cell Lung Cancer | Stage IA Non-small Cell Lung Cancer | Stage IB Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB Non-small Cell Lung CancerCanada
-
Karen KellyBristol-Myers Squibb; National Cancer Institute (NCI); TransgeneCompletedStage IIIA Non-Small Cell Lung Cancer | Stage IIIB Non-Small Cell Lung Cancer | Recurrent Non-Small Cell Lung Carcinoma | Stage IV Non-Small Cell Lung Cancer | Stage I Non-Small Cell Lung Cancer | Stage II Non-Small Cell Lung CancerUnited States
-
Memorial Sloan Kettering Cancer CenterAstraZenecaRecruitingNSCLC | Lung Cancer | Non-small Cell Lung Cancer Stage III | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Stage I | PD-L1 Gene Mutation | Non-small Cell Lung Cancer Stage IIIA | Non-small Cell Lung Cancer Stage IIUnited States
-
Virginia Commonwealth UniversityNational Cancer Institute (NCI)WithdrawnStage IIIA Non-small Cell Lung Cancer | Stage IIIB Non-small Cell Lung Cancer | Recurrent Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB Non-small Cell Lung CancerUnited States
Clinical Trials on TPX-0046
-
OrthoTrophix, IncCompleted
-
Turning Point Therapeutics, Inc.WithdrawnMetastatic Solid Tumor | Locally Advanced Solid TumorUnited States, Spain
-
Turning Point Therapeutics, Inc.RecruitingLymphoma | Locally Advanced Solid Tumors | Metastatic Solid Tumors | Primary CNS TumorsUnited States, Korea, Republic of, Spain, Singapore, Taiwan, Australia, Italy, Canada, France, Denmark, United Kingdom
-
Tego Science, Inc.CompletedRotator Cuff InjuriesKorea, Republic of
-
Turning Point Therapeutics, Inc.Active, not recruitingAdvanced Solid Tumor | Metastatic Solid Tumors | MET Gene AlterationsUnited States, France, Korea, Democratic People's Republic of, Korea, Republic of, Spain
-
Tego Science, Inc.CompletedRotator Cuff InjuriesKorea, Republic of
-
OrthoTrophix, IncCompleted
-
Tego Science, Inc.CompletedTear Trough Eyelid DeformityKorea, Republic of
-
MedSIRMedical University of ViennaNot yet recruitingNSCLC | Brain Metastases | ROS1 Gene Rearrangement
-
OrthoTrophix, IncCompleted