A phase 1/2, first-in-human, open-label study of the safety, tolerability, PK, and efficacy of the novel MET/CSF1R/SRC inhibitor TPX-0022 in adult subjects with advanced or metastatic NSCLC, Gastric Cancer, or solid tumors harboring genetic alterations in MET. (SHIELD-I)
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
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.
Primary outcome measure(s)
Incidence of first cycle dose-limiting toxicities (DLTs) of elzovantinib — Within 28 days of the first elzovantinib dose for each patient Evaluate the safety and tolerability of elzovantinib
Define the Recommended Phase 2 Dose — Approximately 48 months Determine the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of elzovantinib
Trial sites (24)
Facility
City
Region
Status
Local Institution - 2102
La Jolla
California
Local Institution - 2108
Orange
California
Local Institution - 2105
Denver
Colorado
Local Institution - 2111
Chicago
Illinois
Local Institution - 2107
Boston
Massachusetts
Local Institution - 2109
Boston
Massachusetts
Local Institution - 2106
Ann Arbor
Michigan
Local Institution - 2113
Detroit
Michigan
Local Institution - 2103
St Louis
Missouri
Local Institution - 2104
Toledo
Ohio
Local Institution - 2101
Houston
Texas
Local Institution - 2112
Fairfax
Virginia
Local Institution - 4202
La Tronche
Auvergne-Rhône-Alpes
Local Institution - 4203
Saint-Mandé
Val-de-Marne
Local Institution - 4204
Villejuif
Val-de-Marne
Local Institution - 4201
Lyon
France
Local Institution - 6304
Seoul
North Korea
Local Institution - 6301
Seoul
Seoul-teukbyeolsi [Seoul]
Local Institution - 6303
Seoul
South Korea
Local Institution - 6302
Seoul
South Korea
Local Institution - 4104
Madrid
Spain
Local Institution - 4103
Madrid
Spain
Local Institution - 4101
Madrid
Spain
Local Institution - 4102
Pamplona
Spain
More Turning Point Therapeutics, Inc. trials in the USA
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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