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Trial record 1 of 1 for:    TPX-0046 | Medullary Thyroid Cancer
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Study of TPX-0046, A RET/SRC Inhibitor in Adult Subjects With Advanced Solid Tumors Harboring RET Fusions or Mutations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04161391
Recruitment Status : Active, not recruiting
First Posted : November 13, 2019
Last Update Posted : February 13, 2023
Information provided by (Responsible Party):
Turning Point Therapeutics, Inc.

Brief Summary:
A phase 1/2, first-in-human, open-label study to determine the safety, tolerability, PK, and preliminary efficacy of the novel RET/SRC inhibitor TPX-0046 in adult subjects with advanced or metastatic solid tumors harboring RET mutations or alterations. The study consists of three portions: 1) Phase 1 Dose Escalation and Food Effect Sub-study, and 2) Phase 1 dose expansion and 3) Phase 2 efficacy evaluation.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Medullary Thyroid Cancer RET Gene Mutation Metastatic Solid Tumor Advanced Solid Tumor Drug: TPX-0046 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 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-0046, A Novel Oral RET/SRC Inhibitor in Adult Subjects With Advanced/Metastatic Solid Tumors Harboring Oncogenic RET Fusions or Mutations
Actual Study Start Date : December 16, 2019
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : November 2023

Resource links provided by the National Library of Medicine

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:

  • Cohort I (NSCLC + RET fusion, RET TKI Therapy Naive)
  • Cohort II (NSCLC + RET fusion, RET TKI Therapy Pre-treated)
  • Cohort III (MTC + RET mutation, RET TKI Therapy Naive)
  • Cohort IV (MTC + RET mutation, RET TKI Therapy Pre-treated)
  • Cohort V (advanced/metastatic tumor with RET fusion or mutation, RET TKI Therapy Naive)
  • Cohort VI (advanced/metastatic tumor with RET fusion or mutation, RET TKI Therapy Pre-Treated)
Drug: TPX-0046
Oral TPX-0046 capsules

Primary Outcome Measures :
  1. 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

  2. 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

Secondary Outcome Measures :
  1. Adverse events (AEs) [ Time Frame: Approximately 48 months ]
    Evaluate the overall safety profile of TPX-0046

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Age ≥ 18 (or age ≥ 20 as required by local regulation).
  2. 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.
  3. ECOG performance status ≤ 1.
  4. Existence of measurable or evaluable disease (according to Response evaluation criteria in solid tumors [RECIST v1.1] criteria).
  5. Subjects with asymptomatic primary CNS tumors or brain metastases are eligible for the study if they meet protocol specified criteria.
  6. Adequate organ function.
  7. Life expectancy ≥ 12 weeks.

Exclusion Criteria:

  1. Locally advanced solid tumor that is a candidate for curative treatment through radical surgery and/or radiotherapy, or chemotherapy.
  2. 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.
  3. Major surgery within four weeks of the start of therapy.
  4. 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.
  5. 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
  6. Known clinically significant active infections not controlled with systemic treatment (bacterial, fungal, viral including HIV positivity).
  7. Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
  8. Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
  9. Subjects with current or anticipated need for drugs that are sensitive CYP2C9 substrates with narrow therapeutic indices.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04161391

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United States, California
UCI Health - Chao Family Comprehensive Cancer Center
Irvine, California, United States, 92868
UC San Diego Moores Cancer Center
San Diego, California, United States, 92093
United States, Colorado
University of Colorado, Denver
Aurora, Colorado, United States, 80045
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, United States, 80218
United States, District of Columbia
Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Winship Cancer Institute, Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10021
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Virginia
Virginia Cancer Specialists
Fairfax, Virginia, United States, 22031
United States, Washington
The University of Washington, Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Korea, Republic of
Severance Hospital, Yonsei University Health System
Seoul, Korea, Republic of, 03722
Sponsors and Collaborators
Turning Point Therapeutics, Inc.
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Study Director: Turning Point Therapeutics, MD Turning Point Therapeutics
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Responsible Party: Turning Point Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04161391    
Other Study ID Numbers: TPX-0046-01
First Posted: November 13, 2019    Key Record Dates
Last Update Posted: February 13, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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.:
Non small cell lung cancer
Non-small cell lung cancer
Medullary Thyroid Cancer
Advanced non small cell lung cancer
lung cancer
Metastatic solid tumor
Advanced Solid Tumors
Thyroid cancer
RET gene mutation
RET gene alteration
Advanced/metastatic disease
lung adenocarcinoma
RET gene fusion
RET inhibitor
Additional relevant MeSH terms:
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Lung Neoplasms
Thyroid Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Bronchial Neoplasms
Thyroid Diseases
Endocrine Gland Neoplasms
Head and Neck Neoplasms
Carcinoma, Non-Small-Cell Lung
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Endocrine System Diseases