Phase 1 Study of TPX-0022, a MET/CSF1R/SRC Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in MET

• Status: Recruiting
• Trial end date: 2023-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Turning Point Therapeutics, Inc.

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 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.

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 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:

• 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

8. Known clinically significant active infections not controlled with systemic treatment (bacterial, fungal, viral including HIV positivity).

9. Peripheral neuropathy ≥ Grade 2.