Summary

for people ages 18 years and up (full criteria)
at San Diego, California and other locations
study started
estimated completion

Description

Summary

A phase 1, first-in-human, open-label study to determine the safety, tolerability, PK, and preliminary efficacy of the novel MET/CSF1R/SRC inhibitor TPX-0022 in adult subjects with advanced solid tumors harboring genetic alterations in MET. The study will proceed in three parts: a dose-escalation, a food effect, and dose-expansion.

Official Title

A Phase 1, Open-Label, Multi-Center, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of TPX-0022, a Novel MET/CSF1R/SRC Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in MET

Details

Dose Escalation: To evaluate the overall safety profile of TPX-0022, single and multiple dose PK profiles and preliminary efficacy in adults subjects with advanced solid tumors harboring genetic alterations in MET.

Food Effect: To determine the effect of food on PK of TPX-0022 in adult subjects with advanced solid tumors harboring genetic alterations in MET.

Dose Expansion: To evaluate the preliminary efficacy and overall safety profile of TPX-0022 at the RP2D in defined cohorts of adult subjects in advanced solid tumors harboring genetic alterations in MET.

Keywords

Advanced Solid Tumor Metastatic Solid Tumors MET Gene Alterations Non Small Cell Lung Non Small Cell Lung Cancer Non-small cell lung cancer NSCLC TPX-0022 EGFR wild-type (wt) advanced non-small cell lung cancer advanced/metastatic disease Non-small cell lung carcinoma (NSCLC) treatment of lung cancer after first metastasis treatment of gastric cancer after first metastasis treatment of hepatocellular cancer after first metastasis lung cancer lung adenocarcinoma Non small cell lung carcinoma MET exon 14 deletion MET exon 14 skipping MET exon 14 mutation MET mutation MET amplification MET inhibitor MET dysregulation MET activation MET signaling MET pathway MET fusion gastric cancer hepatocellular cancer SRC CSF1R cancer first in human Neoplasms

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Age ≥ 18 (or age ≥ 20 as required by local regulation).
  2. Histological or cytological confirmation of advanced/metastatic solid tumors harboring the genetic MET alteration(s) including exon 14 deletion (METΔex14), amplification, fusion or activating kinase mutation, who are resistant or intolerant to standard therapy or for whom curative therapy is not available. Subjects must have a genetic MET alteration as determined by fluorescence in situ hybridization (FISH), quantitative polymerase chain reaction (qPCR), or next-generation sequencing (NGS).Local tissue-based or liquid biopsy diagnostic testing will be permitted.
  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.

You CAN'T join if...

  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 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. Additional exclusion criteria for subjects with NSCLC with MET alterations: known oncogene drivers (ALK, ROS1, or EGFR) conferring sensitivity to targeted therapies.
  5. Additional exclusion criteria for subjects with HCC with MET alterations: liver dysfunction greater than Child-Pugh Class A.
  6. 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.
  7. Any of the following cardiac criteria:
  8. 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
  9. 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)
  10. 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
  11. Known clinically significant active infections not controlled with systemic treatment (bacterial, fungal, viral including HIV positivity).
  12. Peripheral neuropathy ≥ Grade 2.

Locations

  • University California San Diego Moores Cancer Center accepting new patients
    San Diego California 92093 United States
  • Sarah Cannon Research Institute at HealthONE accepting new patients
    Denver Colorado 80218 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Turning Point Therapeutics, Inc.
ID
NCT03993873
Phase
Phase 1
Study Type
Interventional
Last Updated