Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04161391
Recruitment Status : Recruiting
First Posted : November 13, 2019
Last Update Posted : July 14, 2020
Sponsor:
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 two portions: 1) Phase 1 Dose Escalation and Food Effect Sub-study, and 2) 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: 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 362 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 : May 2024
Estimated Study Completion Date : March 2025


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.

A food-effect sub-study will be conducted once the RP2D has been determined.

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

  3. Define the objective response rate (ORR) [ Time Frame: Approximately 48 months ]
    Determine the preliminary efficacy by the ORR in defined cohorts of subjects with advanced/metastatic solid tumors harboring oncogenic RET fusions or mutations.


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

  2. Cmax (maximum plasma concentration) of TPX-0046 [ Time Frame: Up to 96 hours post-dose ]
    Evaluate the maximum plasma concentration of TPX-0046

  3. AUC (area under plasma concentration time curve) of TPX-0046 [ Time Frame: Up to 96 hours post-dose ]
    Determine the AUC of TPX-0046

  4. Cmax (maximum plasma concentration) of TPX-0046 under different food intake conditions [ Time Frame: Up to 96 hours post-dose ]
    Determine the effect of food (specifically, a high-fat, high-calorie meal) on the single-dose PK (Cmax) of TPX-0046 at the RP2D

  5. AUC (area under plasma concentration time curve) of TPX-0046 under different food intake conditions [ Time Frame: Up to 96 hours post-dose ]
    Determine the effect of food (specifically, a high-fat, high-calorie meal) on the single-dose PK (AUC) of TPX-0046 at the RP2D

  6. Preliminary Objective Response Rate (ORR) [ Time Frame: Approximately 48 months ]
    Determine the preliminary objective response rate (ORR) by Blinded Independent Central Review (BICR) of TPX-0046

  7. Clinical benefit rate (CBR) [ Time Frame: Approximately 48 months ]
    Determine the CBR of TPX-0046

  8. Time to response (TTR) [ Time Frame: Approximately 48 months ]
    Determine the TTR of TPX-0046

  9. Duration of Response (DOR) [ Time Frame: Approximately 48 months ]
    Determine the DOR of TPX-0046

  10. Progression free survival (PFS) [ Time Frame: Approximately 48 months ]
    Determine the PFS of TPX-0046

  11. Intracranial tumor response [ Time Frame: Approximately 48 months ]
    Determine the intracranial tumor response in subjects with measurable brain metastases, as determined by BICR

  12. Overall survival (OS) [ Time Frame: Approximately 48 months ]
    Determine efficacy and safety of TPX-0046



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

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


Contacts
Layout table for location contacts
Contact: Robert Xin, MD, PhD (858) 276-0005 clinical@tptherapeutics.com

Locations
Layout table for location information
United States, California
UCI Health - Chao Family Comprehensive Cancer Center Recruiting
Irvine, California, United States, 92868
Principal Investigator: Viola Zhu, MD         
UC San Diego Moores Cancer Center Recruiting
San Diego, California, United States, 92093
Principal Investigator: Lyudmila Bazhenova, MD         
United States, Colorado
University of Colorado, Denver Recruiting
Aurora, Colorado, United States, 80045
Principal Investigator: Robert Doebele, MD, PhD         
Sarah Cannon Research Institute at HealthONE Recruiting
Denver, Colorado, United States, 80218
Principal Investigator: Gerald Falchook, MD, MS         
United States, District of Columbia
Georgetown University Medical Center Recruiting
Washington, District of Columbia, United States, 20007
Principal Investigator: Stephen Liu, MD         
United States, Georgia
Winship Cancer Institute, Emory University Recruiting
Atlanta, Georgia, United States, 30322
Principal Investigator: Taofeek Owonikoko, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: Jessica Lin, MD         
United States, Michigan
University of Michigan Rogel Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Principal Investigator: Angel Qin, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10021
Principal Investigator: Alexander Drilon, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Vivek Subbiah, MD         
Sponsors and Collaborators
Turning Point Therapeutics, Inc.
Investigators
Layout table for investigator information
Study Director: Robert Xin, MD, PhD Turning Point Therapeutics
Layout table for additonal information
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: July 14, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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
NSCLC
Medullary Thyroid Cancer
MTC
RET gene mutation
RET gene alteration
Advanced non small cell lung cancer
Advanced/metastatic disease
lung cancer
lung adenocarcinoma
Metastatic solid tumor
Advanced Solid Tumors
RET gene fusion
RET inhibitor
SRC
TPX-0046
Thyroid cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Thyroid Neoplasms
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Thyroid Diseases
Endocrine System Diseases
Endocrine Gland Neoplasms
Head and Neck Neoplasms