Study of TPX-0022 in Patients With Advanced NSCLC, Gastric Cancer or Solid Tumors Harboring Genetic Alterations in MET (SHIELD-1)
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|ClinicalTrials.gov Identifier: NCT03993873|
Recruitment Status : Recruiting
First Posted : June 21, 2019
Last Update Posted : May 3, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Advanced Solid Tumor Metastatic Solid Tumors MET Gene Alterations||Drug: elzovantinib (TPX-0022)||Phase 1 Phase 2|
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 (Clinical Trial)|
|Estimated Enrollment :||180 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||September 21, 2019|
|Estimated Primary Completion Date :||November 30, 2023|
|Estimated Study Completion Date :||November 30, 2023|
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
- Incidence of first cycle dose-limiting toxicities (DLTs) of elzovantinib [ Time Frame: Within 28 days of the first elzovantinib dose for each patient ]Evaluate the safety and tolerability of elzovantinib
- Define the Recommended Phase 2 Dose [ Time Frame: Approximately 48 months ]Determine the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of elzovantinib
- Adverse events (AEs) [ Time Frame: Approximately 48 months ]Evaluate the overall safety profile of elzovantinib
- Cmax (maximum plasma concentration) of elzovantinib [ Time Frame: Up to 72 hours post-dose ]Evaluate the maximum plasma concentration of elzovantinib
- AUC (area under plasma concentration time curve) of elzovantinib [ Time Frame: Up to 72 hours post-dose ]Evaluate the AUC of elzovantinib
- Cmax (maximum plasma concentration) of TPX-0022 under different food intake conditions [ Time Frame: Up to 72 hours post-dose ]Determine the effect of food (specifically, a high-fat, high-calorie meal) on the single-dose PK (Cmax) of elzovantinib at the RP2D
- AUC (area under plasma concentration time curve) of elzovantinib under different food intake conditions [ Time Frame: Up to 72 hours post-dose ]Determine the effect of food (specifically, a high-fat, high-calorie meal) on the single-dose PK (AUC) of elzovantinib at the RP2D
- Preliminary Objective Response Rate (ORR) [ Time Frame: Approximately 48 months ]Determine the preliminary objective response rate (ORR) by Blinded Independent Central Review (BICR) of elzovantinib
- Clinical benefit rate (CBR) [ Time Frame: Approximately 48 months ]Determine the CBR of elzovantinib
- Time to response (TTR) [ Time Frame: Approximately 48 months ]Determine the TTR of elzovantinib
- Duration of Response (DOR) [ Time Frame: Approximately 48 months ]Determine the DOR of elzovantinib
- Progression free survival (PFS) [ Time Frame: Approximately 48 months ]Determine the PFS of elzovantinib
- Intracranial tumor response [ Time Frame: Approximately 48 months ]Determine the intracranial tumor response in subjects with measurable brain metastases, as determined by BICR
- Overall survival (OS) [ Time Frame: Approximately 48 months ]Determine efficacy and safety of elzovantinib
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
- 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.
- 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.
- Additional exclusion criteria for subjects with HCC with MET alterations: liver dysfunction greater than Child-Pugh Class A.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03993873
|Contact: BMS Study Connect Contact Center www.BMSStudyConnect.com||855-907-3286||Clinical.Trials@bms.com|
|Contact: First line of the email MUST contain the NCT# and Site #.|
|Study Director:||Bristol-Myers Squibb||Bristol-Myers Squibb|
|Responsible Party:||Turning Point Therapeutics, Inc.|
|Other Study ID Numbers:||
CA177-1036 ( Other Identifier: Bristol-Myers Squibb Protocol ID )
TPX-0022-01 ( Other Identifier: Turning Point Therapeutics Protocol ID )
|First Posted:||June 21, 2019 Key Record Dates|
|Last Update Posted:||May 3, 2023|
|Last Verified:||May 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Non Small Cell Lung
Non Small Cell Lung Cancer
Non-small cell lung cancer
EGFR wild-type (wt)
advanced non-small cell lung cancer
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
Non small cell lung carcinoma
MET exon 14 deletion
MET exon 14 skipping
MET exon 14 mutation
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases