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

Advanced Solid Tumor Clinical Trial

— SHIELD-1  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03993873
• Other study ID #: CA177-1036
• Secondary ID: CA177-1036TPX-00
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: September 21, 2019
• Est. completion date: March 2, 2025

Study information

• Verified date: November 2023
• Source: Turning Point Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 180
• Est. completion date: March 2, 2025
• Est. primary completion date: March 2, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (MET?ex14) 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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• MET Gene Alterations
• Metastatic Solid Tumors
• Neoplasms
• Stomach Neoplasms

Intervention

Drug:
• elzovantinib (TPX-0022)
Oral elzovantinib (TPX-0022) capsules

Locations

Country	Name	City	State
France	Local Institution - 4202	La Tronche	Rhone-Alpes
France	Local Institution - 4201	Lyon	Rhone-Alpes
France	Local Institution - 4203	Saint-Mandé	Val-de-Marne
France	Local Institution - 4204	Villejuif	Val-de-Marne
Korea, Democratic People's Republic of	Local Institution - 6304	Seoul
Korea, Republic of	Local Institution - 6301	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Local Institution - 6302	Seoul
Korea, Republic of	Local Institution - 6303	Seoul
Spain	Local Institution - 4101	Madrid
Spain	Local Institution - 4103	Madrid
Spain	Local Institution - 4104	Madrid
Spain	Local Institution - 4102	Pamplona
United States	Local Institution - 2106	Ann Arbor	Michigan
United States	Local Institution - 2107	Boston	Massachusetts
United States	Local Institution - 2109	Boston	Massachusetts
United States	Local Institution - 2111	Chicago	Illinois
United States	Local Institution - 2105	Denver	Colorado
United States	Local Institution - 2113	Detroit	Michigan
United States	Local Institution - 2112	Fairfax	Virginia
United States	Local Institution - 2101	Houston	Texas
United States	Local Institution - 2102	La Jolla	California
United States	Local Institution - 2108	Orange	California
United States	Local Institution - 2103	Saint Louis	Missouri
United States	Local Institution - 2104	Toledo	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Turning Point Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  France,  Korea, Democratic People's Republic of,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Adverse events (AEs)	Evaluate the overall safety profile of elzovantinib	Approximately 48 months
Secondary	Cmax (maximum plasma concentration) of elzovantinib	Evaluate the maximum plasma concentration of elzovantinib	Up to 72 hours post-dose
Secondary	AUC (area under plasma concentration time curve) of elzovantinib	Evaluate the AUC of elzovantinib	Up to 72 hours post-dose
Secondary	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
Secondary	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
Secondary	Preliminary Objective Response Rate (ORR)	Determine the preliminary objective response rate (ORR) by Blinded Independent Central Review (BICR) of elzovantinib	Approximately 48 months
Secondary	Clinical benefit rate (CBR)	Determine the CBR of elzovantinib	Approximately 48 months
Secondary	Time to response (TTR)	Determine the TTR of elzovantinib	Approximately 48 months
Secondary	Duration of Response (DOR)	Determine the DOR of elzovantinib	Approximately 48 months
Secondary	Progression free survival (PFS)	Determine the PFS of elzovantinib	Approximately 48 months
Secondary	Intracranial tumor response	Determine the intracranial tumor response in subjects with measurable brain metastases, as determined by BICR	Approximately 48 months
Secondary	Overall survival (OS)	Determine efficacy and safety of elzovantinib	Approximately 48 months

External Links

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