Clinical Trials /

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

NCT03993873

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Carcinoma
  • Hepatocellular Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: TPX-0022-01
  • NCT ID: NCT03993873

Conditions

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

Interventions

DrugSynonymsArms
TPX-0022Phase 1 TPX-0022

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1 TPX-0022ExperimentalThe 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)
  • TPX-0022

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Evaluate the safety and tolerability of TPX-0022

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Turning Point Therapeutics, Inc.

Trial Keywords

  • 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
  • cancer
  • first in human

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