Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
Inclusion Criteria:
1. Age ≥ 18 (or age ≥ 20 as required by local regulation).
2. Histological or cytological confirmation of advanced/metastatic MET exon 14 skipping
mutation (METΔex14) NSCLC, MET amplified NSCLC, or MET amplified gastric cancers as
determined by FISH, qPCR or NGS by local liquid biopsy or tissue, solid tumors with
MET fusions or oncogenic MET mutations or MET amplified other than GI/NSCLC.
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 within the past 3 years 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 mutations (eg, ALK, ROS1, KRAS, EGFR, etc.) for which there are approved
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.
