Study of TPX-0022 in Patients With Advanced NSCLC, Gastric Cancer or Solid Tumors Harboring Genetic Alterations in MET

NCT03993873 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: CA177-1036TPX-0022-01
• Study Type: interventional
• Target: 95
• Locations: 5 countries
• Sites: 24

Brief Summary

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)

Conditions

Advanced Solid Tumor; Metastatic Solid Tumors; MET Gene Alterations

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Incidence of first cycle dose-limiting toxicities (DLTs) of elzovantinib

  Evaluate the safety and tolerability of elzovantinib

  Within 28 days of the first elzovantinib dose for each patient

• Define the Recommended Phase 2 Dose

  Determine the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of elzovantinib

  Approximately 48 months

Secondary Outcomes (12)

• Adverse events (AEs)

  Approximately 48 months

• Cmax (maximum plasma concentration) of elzovantinib

  Up to 72 hours post-dose

• AUC (area under plasma concentration time curve) of elzovantinib

  Up to 72 hours post-dose

• Cmax (maximum plasma concentration) of TPX-0022 under different food intake conditions

  Up to 72 hours post-dose

• AUC (area under plasma concentration time curve) of elzovantinib under different food intake conditions

  Up to 72 hours post-dose

Study Arms (1)

Phase 1 elzovantinib

EXPERIMENTAL

The dose-escalation part of the study will determine the safety, tolerability, MTD, and RP2D of elzovantinib. The dose-expansion part of the study will determine the safety, tolerability, PK, and preliminary efficacy in specific cohorts. Dose expansion cohorts: Cohort I (NSCLC, METΔex14, treatment Naive) Enrollment Closed; Cohort II (NSCLC with METΔex14, MET therapy pre-treated) Enrollment closed; Cohort III (MET amplified NSCLC, GCN≥10); Cohort IV (MET amplified GI cancer GC/GEJ, CRC/HCC, GCN≥10); Cohort V (NSCLC or GI MET amplified, GCN≥5 and \< 10); Cohort VI (Solid tumors with MET fusions, or oncogenic MET mutations or MET amplified other than GI/NSCLC

Drug: elzovantinib (TPX-0022)

Interventions

elzovantinib (TPX-0022) DRUG

Oral elzovantinib (TPX-0022) capsules

Phase 1 elzovantinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 (or age ≥ 20 as required by local regulation).
• 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.
• ECOG performance status ≤ 1.
• Existence of measurable or evaluable disease (according to Response evaluation criteria in solid tumors \[RECIST v1.1\] criteria).
• Subjects with asymptomatic primary CNS tumors or brain metastases are eligible for the study if they meet protocol specified criteria.
• Adequate organ function.
• Life expectancy ≥ 12 weeks.

You may not qualify if:

• Locally advanced solid tumor that is a candidate for curative treatment through radical surgery and/or radiotherapy, or chemotherapy.
• 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.
• Major surgery within four weeks of the start of therapy.
• 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.
• 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
• Known clinically significant active infections not controlled with systemic treatment (bacterial, fungal, viral including HIV positivity).
• Peripheral neuropathy ≥ Grade 2.

Sponsors & Collaborators

• Turning Point Therapeutics, Inc.: lead

Study Sites (24)

Local Institution - 2102

La Jolla, California, 92093, United States

Location

Local Institution - 2108

Orange, California, 92868, United States

Location

Local Institution - 2105

Denver, Colorado, 80218, United States

Location

Local Institution - 2111

Chicago, Illinois, 60637, United States

Location

Local Institution - 2107

Boston, Massachusetts, 02114, United States

Location

Local Institution - 2109

Boston, Massachusetts, 02215, United States

Location

Local Institution - 2106

Ann Arbor, Michigan, 48109, United States

Location

Local Institution - 2113

Detroit, Michigan, 48202, United States

Location

Local Institution - 2103

St Louis, Missouri, 63110, United States

Location

Local Institution - 2104

Toledo, Ohio, 43614, United States

Location

Local Institution - 2101

Houston, Texas, 77030-4009, United States

Location

Local Institution - 2112

Fairfax, Virginia, 22031, United States

Location

Local Institution - 4202

La Tronche, Auvergne-Rhône-Alpes, 38700, France

Location

Local Institution - 4203

Saint-Mandé, Val-de-Marne, 94160, France

Location

Local Institution - 4204

Villejuif, Val-de-Marne, 94805, France

Location

Local Institution - 4201

Lyon, 69008, France

Location

Local Institution - 6304

Seoul, 05505, North Korea

Location

Local Institution - 6301

Seoul, Seoul-teukbyeolsi [Seoul], 06351, South Korea

Location

Local Institution - 6303

Seoul, 03080, South Korea

Location

Local Institution - 6302

Seoul, 120-752, South Korea

Location

Local Institution - 4104

Madrid, 28036, Spain

Location

Local Institution - 4103

Madrid, 28040, Spain

Location

Local Institution - 4101

Madrid, 28050, Spain

Location

Local Institution - 4102

Pamplona, 31008, Spain

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Lung Neoplasms; Adenocarcinoma of Lung; Stomach Neoplasms; Liver Neoplasms; Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Liver Diseases

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2019
• First Posted: June 21, 2019
• Study Start: September 5, 2019
• Primary Completion: January 8, 2024
• Study Completion (Estimated): March 3, 2027
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

KR (3); FR (4); US (12); NO (1); ES (4)