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.
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.
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.
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
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.