Study of TPX-0046, A RET/SRC Inhibitor in Adult Subjects With Advanced Solid Tumors Harboring RET Fusions or Mutations

May 21, 2024 updated by: Turning Point Therapeutics, Inc.

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
41

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of, 120-752
        • Local Institution - 6320
  • United States
    • California
      • La Jolla, California, United States, 92093
        • 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
        • Local Institution - 2137
    • 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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Dose Limiting Toxicities (DLTs) of TPX-0046
Time Frame: 28 days following the first highest dose of the dose regimen administered in Cycle 1

Participants are eligible for DLT evaluation if they experience a DLT after at least one dose of TPX-0046, or do not experience a DLT after taking at least 75% of the doses expected during the DLT evaluation period. Some adverse events, graded using Common Terminology for Adverse Events (CTCAE) v. 5.0, for defining DLTs include:

  • Toxicities resulting in an excessive number of missed doses;
  • Hematologic: CTCAE grade ≥ 4 neutropenia, CTCAE grade ≥ 4 platelet count decrease, CTCAE grade ≥ 4 anemia, CTCAE grade ≥ 3 febrile neutropenia;
  • Renal: CTCAE grade ≥ 3 creatinine increase;
  • Hepatic: CTCAE grade ≥ 3 total bilirubin elevation;
  • Pancreatic: CTCAE grade 3 serum amylase or lipase increased with clinical symptoms or any grade ≥ serum amylase;
  • Cardiac: CTCAE grade ≥ 3;
  • Other AEs: CTCAE grade 3 vomiting or nausea that does not resolve to grade ≤ 1 within 4 days despite optimal anti-emetic therapy or any grade ≥ 4 vomiting
28 days following the first highest dose of the dose regimen administered in Cycle 1
Maximum Tolerated Dose (MTD) of TPX-0046
Time Frame: 28 days following the first highest dose of the dose regimen administered in Cycle 1
The MTD is defined as the highest dose level of TPX-0046 observed to cause a dose limiting toxicity (DLT) in fewer than 33% of the treated participants in the first treatment cycle (ie, Cycle 1, 28 days).
28 days following the first highest dose of the dose regimen administered in Cycle 1

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Turning Point Therapeutics, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 6, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 22, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 22, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 11, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 11, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 13, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 13, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 21, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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.

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