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

Stopped early · Phase 1/Phase 2

Conditions studied: Non Small Cell Lung Cancer, Medullary Thyroid Cancer, RET Gene Mutation, Metastatic Solid Tumor, Advanced Solid Tumor

In brief

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.

Key facts

Study ID

NCT04161391

Run by

Turning Point Therapeutics, Inc.

People needed

41

Starts

2019-12-06

Expected to finish

2023-05-22

Last updated by the study team

2024-06-13

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• 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.

Where it is running

• Local Institution - 2129 — La Jolla, California, United States
• Local Institution - 2128 — Orange, California, United States
• Local Institution - 2122 — Aurora, Colorado, United States
• SCRI - HealthOne Denver — Denver, Colorado, United States
• Local Institution - 2126 — Washington D.C., District of Columbia, United States
• Mayo Clinic - Jacksonville — Jacksonville, Florida, United States
• Local Institution - 2130 — Tampa, Florida, United States
• Local Institution - 2127 — Atlanta, Georgia, United States
• University of Chicago Medicine — Chicago, Illinois, United States
• Massachusetts General Hospital — Boston, Massachusetts, United States
• Local Institution - 2124 — Ann Arbor, Michigan, United States
• Local Institution - 2131 — Detroit, Michigan, United States
• Mayo Clinic - Arizona — Rochester, Minnesota, United States
• Mayo Clinic - Rochester — Rochester, Minnesota, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• Local Institution - 2137 — Philadelphia, Pennsylvania, United States
• Local Institution - 2120 — Houston, Texas, United States
• Baylor College of Medicine - Baylor Heart Clinic — Houston, Texas, United States
• Local Institution - 2135 — Fairfax, Virginia, United States
• Local Institution - 2132 — Seattle, Washington, United States
• Local Institution - 6320 — Seoul, South Korea

Full record on ClinicalTrials.gov

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