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Trial record 1 of 1 for:    TPX-0022
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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 : April 8, 2022
Sponsor:
Information provided by (Responsible Party):
Turning Point Therapeutics, Inc.

Brief Summary:
A phase 1/2, first-in-human, open-label study to determine the safety, tolerability, PK, and preliminary efficacy of the novel MET/CSF1R/SRC inhibitor TPX-0022 in adult subjects with advanced NSCLC, Gastric Cancer, or solid tumors harboring genetic alterations in MET. The study will proceed in two parts: a dose-escalation and dose-expansion.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Metastatic Solid Tumors MET Gene Alterations Drug: TPX-0022 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 330 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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 : August 20, 2019
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : November 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Stomach Cancer

Arm Intervention/treatment
Experimental: Phase 1 TPX-0022

The dose-escalation part of the study will determine the safety, tolerability, MTD, and RP2D of TPX-0022.

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), Cohort II (NSCLC with METΔex14, 1 or 2 lines prior systemic therapy, no prior MET TKI), Cohort III (NSCLC with METΔex14, MET TKI-pretreated, up to 2 additional lines of prior systemic therapy Cohort IV (MET amplified NSCLC, received 1 or 2 lines of prior systemic therapy, no prior MET TKI) Cohort V (MET amplified Gastric or GEJ Cancer, received 1 line of prior systemic therapy, no prior MET TKI Cohort VI (MET amplified Gastric or GEJ Cancer, received 2 lines prior systemic therapy, no prior MET TKI Exploratory Cohort VII (MET amplified NSCLC or Gastric/GEJ Cancer with gene copy number (GCN ≥ 5 and < 10), received 1 or 2 lines of prior systemic therapy, no prior MET TKI

Drug: TPX-0022
Oral TPX-0022 tablets or capsules




Primary Outcome Measures :
  1. Incidence of first cycle dose-limiting toxicities (DLTs) of TPX-0022 [ Time Frame: Within 28 days of the first TPX-0022 dose for each patient ]
    Evaluate the safety and tolerability of TPX-0022

  2. 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 TPX-0022


Secondary Outcome Measures :
  1. Adverse events (AEs) [ Time Frame: Approximately 48 months ]
    Evaluate the overall safety profile of TPX-0022

  2. Cmax (maximum plasma concentration) of TPX-0022 [ Time Frame: Up to 72 hours post-dose ]
    Evaluate the maximum plasma concentration of TPX-0022

  3. AUC (area under plasma concentration time curve) of TPX-0022 [ Time Frame: Up to 72 hours post-dose ]
    Evaluate the AUC of TPX-0022

  4. 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 TPX-0022 at the RP2D

  5. AUC (area under plasma concentration time curve) 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 (AUC) of TPX-0022 at the RP2D

  6. Preliminary Objective Response Rate (ORR) [ Time Frame: Approximately 48 months ]
    Determine the preliminary objective response rate (ORR) by Blinded Independent Central Review (BICR) of TPX-0022

  7. Clinical benefit rate (CBR) [ Time Frame: Approximately 48 months ]
    Determine the CBR of TPX-0022

  8. Time to response (TTR) [ Time Frame: Approximately 48 months ]
    Determine the TTR of TPX-0022

  9. Duration of Response (DOR) [ Time Frame: Approximately 48 months ]
    Determine the DOR of TPX-0022

  10. Progression free survival (PFS) [ Time Frame: Approximately 48 months ]
    Determine the PFS of TPX-0022

  11. Intracranial tumor response [ Time Frame: Approximately 48 months ]
    Determine the intracranial tumor response in subjects with measurable brain metastases, as determined by BICR

  12. Overall survival (OS) [ Time Frame: Approximately 48 months ]
    Determine efficacy and safety of TPX-0022



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  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 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 drivers (ALK, ROS1, or EGFR) conferring sensitivity to targeted 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.

Information from the National Library of Medicine

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


Contacts
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Contact: Turning Point Therapeutics Medical Information +1 855-427-5878 medinfo@tptherapeutics.com

Locations
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Sponsors and Collaborators
Turning Point Therapeutics, Inc.
Investigators
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Study Director: Turning Point Therapeutics Medical Information Turning Point Therapeutics, Inc.
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Responsible Party: Turning Point Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03993873    
Other Study ID Numbers: TPX-0022-01
First Posted: June 21, 2019    Key Record Dates
Last Update Posted: April 8, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Turning Point Therapeutics, Inc.:
TPX-0022
Non Small Cell Lung
Non Small Cell Lung Cancer
Non-small cell lung cancer
NSCLC
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
Additional relevant MeSH terms:
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Neoplasms
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases