Study of TPX-0022 in Patients With Advanced NSCLC, Gastric Cancer or Solid Tumors Harboring Genetic Alterations in MET (SHIELD-1)

A Phase 1/2 of Study of the Safety, Tolerability, Pharmacokinetics, and Efficacy of TPX-0022 in Adult Subjects With Locally Advanced or Metastatic NSCLC, Gastric Cancer, or Solid Tumors Harboring Genetic Alterations in MET

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)

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Solid Tumor; Metastatic Solid Tumors; MET Gene Alterations
• Intervention / Treatment: Drug: elzovantinib (TPX-0022)

Detailed Description

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.

Dose Expansion: To evaluate the preliminary efficacy and overall safety profile of TPX-0022 at the RP2D in defined cohorts of adult subjects in NSCLC, Gastric Cancer and advanced solid tumors harboring genetic alterations in MET.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: BMS Study Connect Contact Center www.BMSStudyConnect.com; Phone Number: 855-907-3286; Email: Clinical.Trials@bms.com
• Study Contact Backup: Name: First line of the email MUST contain the NCT# and Site #.

Study Locations

• France
  • Rhone-Alpes
    • La Tronche, Rhone-Alpes, France, 38700
      • Local Institution - 4202
    • Lyon, Rhone-Alpes, France, 69008
      • Local Institution - 4201
  • Val-de-Marne
    • Saint-Mandé, Val-de-Marne, France, 94160
      • Local Institution - 4203
    • Villejuif, Val-de-Marne, France, 94805
      • Local Institution - 4204
• Korea, Democratic People's Republic of
  • Seoul, Korea, Democratic People's Republic of, 05505
    • Local Institution - 6304
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Local Institution - 6303
  • Seoul, Korea, Republic of, 120-752
    • Local Institution - 6302
  • Seoul-teukbyeolsi [Seoul]
    • Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of, 06351
      • Local Institution - 6301
• Spain
  • Madrid, Spain, 28036
    • Local Institution - 4104
  • Madrid, Spain, 28040
    • Local Institution - 4103
  • Madrid, Spain, 28050
    • Local Institution - 4101
  • Pamplona, Spain, 31008
    • Local Institution - 4102
• United States
  • California
    • La Jolla, California, United States, 92093
      • Local Institution - 2102
    • Orange, California, United States, 92868
      • Local Institution - 2108
  • Colorado
    • Denver, Colorado, United States, 80218
      • Local Institution - 2105
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Local Institution - 2111
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Local Institution - 2107
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 2109
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Local Institution - 2106
    • Detroit, Michigan, United States, 48202
      • Local Institution - 2113
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Local Institution - 2103
  • Ohio
    • Toledo, Ohio, United States, 43614
      • Local Institution - 2104
  • Texas
    • Houston, Texas, United States, 77030-4009
      • Local Institution - 2101
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Local Institution - 2112

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Phase 1 elzovantinib; 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); Oral elzovantinib (TPX-0022) capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial tumor response	Determine the intracranial tumor response in subjects with measurable brain metastases, as determined by BICR	Approximately 48 months
Adverse events (AEs)	Evaluate the overall safety profile of elzovantinib	Approximately 48 months
Cmax (maximum plasma concentration) of elzovantinib	Evaluate the maximum plasma concentration of elzovantinib	Up to 72 hours post-dose
AUC (area under plasma concentration time curve) of elzovantinib	Evaluate the AUC of elzovantinib	Up to 72 hours post-dose
Cmax (maximum plasma concentration) of TPX-0022 under different food intake conditions	Determine the effect of food (specifically, a high-fat, high-calorie meal) on the single-dose PK (Cmax) of elzovantinib at the RP2D	Up to 72 hours post-dose
AUC (area under plasma concentration time curve) of elzovantinib under different food intake conditions	Determine the effect of food (specifically, a high-fat, high-calorie meal) on the single-dose PK (AUC) of elzovantinib at the RP2D	Up to 72 hours post-dose
Preliminary Objective Response Rate (ORR)	Determine the preliminary objective response rate (ORR) by Blinded Independent Central Review (BICR) of elzovantinib	Approximately 48 months
Clinical benefit rate (CBR)	Determine the CBR of elzovantinib	Approximately 48 months
Time to response (TTR)	Determine the TTR of elzovantinib	Approximately 48 months
Duration of Response (DOR)	Determine the DOR of elzovantinib	Approximately 48 months
Progression free survival (PFS)	Determine the PFS of elzovantinib	Approximately 48 months
Overall survival (OS)	Determine efficacy and safety of elzovantinib	Approximately 48 months

Collaborators and Investigators

• Sponsor: Turning Point Therapeutics, Inc.
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2019
• Primary Completion (Estimated): March 2, 2025
• Study Completion (Estimated): March 2, 2025

Study Registration Dates

• First Submitted: June 13, 2019
• First Submitted That Met QC Criteria: June 19, 2019
• First Posted (Actual): June 21, 2019

Study Record Updates

• Last Update Posted (Estimated): November 20, 2023
• Last Update Submitted That Met QC Criteria: November 16, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC; lung cancer; cancer; Non Small Cell Lung Cancer; Non-small cell lung cancer; gastric cancer; CSF1R; MET amplification; MET mutation; lung adenocarcinoma; Non Small Cell Lung; 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; Non small cell lung carcinoma; MET exon 14 deletion; MET exon 14 skipping; MET exon 14 mutation; MET inhibitor; MET dysregulation; MET activation; MET signaling; MET pathway; SRC; first in human; TPX-0022; treatment of gastric cancer after first metastasis; treatment of hepatocellular cancer after first metastasis; MET fusion; hepatocellular cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Neoplasms; Stomach Neoplasms
• Other Study ID Numbers: CA177-1036 (Other Identifier: Bristol-Myers Squibb Protocol ID); TPX-0022-01 (Other Identifier: Turning Point Therapeutics Protocol ID)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No