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Phase 1 Study of TPX-0022, a MET/CSF1R/SRC Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in MET

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ClinicalTrials.gov Identifier: NCT03993873
Recruitment Status : Recruiting
First Posted : June 21, 2019
Last Update Posted : August 19, 2019
Sponsor:
Information provided by (Responsible Party):
Turning Point Therapeutics, Inc.

Brief Summary:
A phase 1, 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 solid tumors harboring genetic alterations in MET. The study will proceed in three parts: a dose-escalation, a food effect, and dose-expansion.

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

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.

Food Effect: To determine the effect of food on PK of TPX-0022 in adult 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 advanced solid tumors harboring genetic alterations in MET.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Multi-Center, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of TPX-0022, a Novel MET/CSF1R/SRC Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in MET
Estimated Study Start Date : December 2019
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : November 2023

Resource links provided by the National Library of Medicine


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.

A food-effect sub-study will be conducted once the RP2D has been determined.

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, MET Target Therapy Naive), Cohort II (NSCLC, METΔex14, MET Target Therapy Pre-treated), Cohort III (MET-amplified NSCLC, Hepatocellular Carcinoma (HCC), Gastric Cancer, or GEJ, Cohort IV (MET KD Mutations or MET Fusions)

Drug: TPX-0022
Oral TPX-0022 tablets




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 solid tumors harboring the genetic MET alteration(s) including exon 14 deletion (METΔex14), amplification, fusion or activating kinase mutation, who are resistant or intolerant to standard therapy or for whom curative therapy is not available. Subjects must have a genetic MET alteration as determined by fluorescence in situ hybridization (FISH), quantitative polymerase chain reaction (qPCR), or next-generation sequencing (NGS).Local tissue-based or liquid biopsy diagnostic testing will be permitted.
  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: Zach Zimmerman, MD, PhD 858-926-5251 clinical@tptherapeutics.com

Locations
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United States, California
University California San Diego Moores Cancer Center Not yet recruiting
San Diego, California, United States, 92093
Contact: Lyudmila Bazhenova, MD         
United States, Colorado
Sarah Cannon Research Institute at HealthONE Recruiting
Denver, Colorado, United States, 80218
Contact: Shiraj Sen, MD, PhD         
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Rebecca Heist, MD, MPH         
United States, Michigan
University of Michigan Rogel Cancer Center Not yet recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Shirish Gadgeel, MD         
United States, Missouri
Washington University School of Medicine in St. Louis Not yet recruiting
Saint Louis, Missouri, United States, 63110
Contact: Haeseong Park, MD, MPH         
United States, Ohio
University of Toledo Medical Center Recruiting
Toledo, Ohio, United States, 43614
Contact: John Nemunaitis, MD         
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: David S Hong, MD         
Sponsors and Collaborators
Turning Point Therapeutics, Inc.
Investigators
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Study Director: Zach Zimmerman, MD, PhD Turning Point Therapeutics, Inc.

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Responsible Party: Turning Point Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03993873     History of Changes
Other Study ID Numbers: TPX-0022-01
First Posted: June 21, 2019    Key Record Dates
Last Update Posted: August 19, 2019
Last Verified: August 2019
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.:
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

Additional relevant MeSH terms:
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Neoplasms