Study of TPX-0046, A RET/SRC Inhibitor in Adult Subjects With Advanced Solid Tumors Harboring RET Fusions or Mutations
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|ClinicalTrials.gov Identifier: NCT04161391|
Recruitment Status : Active, not recruiting
First Posted : November 13, 2019
Last Update Posted : May 3, 2023
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|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|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||41 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
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
- 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
- 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
- Adverse events (AEs) [ Time Frame: Approximately 48 months ]Evaluate the overall safety profile of TPX-0046
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
- 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.
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
|Study Director:||Bristol-Myers Squibb||Bristol-Myers Squibb|
|Responsible Party:||Turning Point Therapeutics, Inc.|
|Other Study ID Numbers:||
CA129-1036 ( Other Identifier: Bristol-Myers Squibb Protocol ID )
TPX-0046-01 ( Other Identifier: Turning Point Therapeutics Protocol ID )
|First Posted:||November 13, 2019 Key Record Dates|
|Last Update Posted:||May 3, 2023|
|Last Verified:||May 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Non small cell lung cancer
Non-small cell lung cancer
Medullary Thyroid Cancer
RET gene mutation
RET gene alteration
Advanced non small cell lung cancer
Metastatic solid tumor
Advanced Solid Tumors
RET gene fusion
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Endocrine System Diseases
Endocrine Gland Neoplasms
Head and Neck Neoplasms