Clinical Trials /

A Study of Tepotinib Plus Osimertinib in Epidermal Growth Factor Receptor (EGFR ) Tyrosine Kinase Inhibitor (TKI) Relapsed Mesenchymal-epithelial Transition Factor (MET) Amplified Non-small Cell Lung Cancer (NSCLC)

NCT03940703

Description:

This study will assess the antitumor activity, safety, tolerability, and pharmacokinetics (PK) of the MET inhibitor tepotinib combined with the 3rd generation EGFR inhibitor osimertinib in participants with advanced or metastatic NSCLC.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Tepotinib Plus Osimertinib in Epidermal Growth Factor Receptor (EGFR ) Tyrosine Kinase Inhibitor (TKI) Relapsed Mesenchymal-epithelial Transition Factor (MET) Amplified Non-small Cell Lung Cancer (NSCLC)
  • Official Title: A Phase II Single-arm Study to Investigate Tepotinib Combined With Osimertinib in MET Amplified, Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) Harboring Activating EGFR Mutations and Having Acquired Resistance to Prior 1st to 3rd Generation EGFR-tyrosine Kinase Inhibitor Therapy

Clinical Trial IDs

  • ORG STUDY ID: MS200095_0031
  • SECONDARY ID: 2019-001538-33
  • NCT ID: NCT03940703

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
TepotinibTepotinib and Osimertinib
OsimertinibTagrisso®Tepotinib and Osimertinib

Purpose

This study will assess the antitumor activity, safety, tolerability, and pharmacokinetics (PK) of the MET inhibitor tepotinib combined with the 3rd generation EGFR inhibitor osimertinib in participants with advanced or metastatic NSCLC.

Trial Arms

NameTypeDescriptionInterventions
Tepotinib and OsimertinibExperimentalParticipants will receive a combination of tepotinib and osimertinib. The combination will be applied in cycles of 21 days until disease progression, death and adverse event leading to discontinuation, study withdrawal or consent withdrawal.
  • Tepotinib
  • Osimertinib

Eligibility Criteria

        Inclusion Criteria:

          -  Locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) histology (confirmed
             by either histology or cytology) with documented activating mutation of the Epidermal
             Growth Factor Receptor (EGFR) receptor including T790 mutation status

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a minimum
             life expectancy of 12 weeks

          -  Acquired resistance on previous EGFR-Tyrosine Kinase Inhibitors (EGFR-TKI) therapy.

          -  MET amplification

          -  Other protocol defined inclusion criteria could apply

        Exclusion Criteria:

          -  Spinal cord compression or brain metastasis unless asymptomatic, stable or not
             requiring steroids for at least 2 weeks prior to start of study intervention

          -  Any unresolved toxicity Grade 2 or more according to National cancer institute common
             terminology criteria for adverse events( NCI-CTCAE) version 5, from previous
             anticancer therapy with the exception of alopecia

          -  Inadequate hematological, liver and renal function

          -  Impaired cardiac function

          -  History of interstitial lung disease(ILD) or interstitial pneumonitis including
             radiation pneumonitis that required steroid treatment

          -  Hypertension uncontrolled by standard therapies (not stabilized to < 150/90 millimeter
             of mercury (mmHg)

          -  Contraindication to the administration of osimertinib

          -  Other protocol defined exclusion criteria could apply
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety run-in: Number of Participants Experiencing Dose Limiting Toxicities (DLT) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version (NCI-CTCAE v 5.0)
Time Frame:Up to Day 21 of Cycle 1 (each Cycle is of 21 days)
Safety Issue:
Description:Participants are identified as having an objective response if they achieve either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progression disease (PD) according to determined according to RECIST 1.1 as adjudicated by the IRC. CR: Complete Response defined as disappearance of all target and non target lesions and any pathological lymph nodes (whether target or non target) must have reduction in short axis to less than (<) 10 mm. Partial response defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.

Secondary Outcome Measures

Measure:Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment-Related Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0, and Deaths
Time Frame:Baseline up to 30 days after the last dose of study treatment (approximately 10.5 months)
Safety Issue:
Description:
Measure:Percentage of Participants With Abnormal greater Than or Equal to (>=) Grade 3 Laboratory Findings
Time Frame:Baseline up to 30 days after the last dose of study treatment (approximately 10.5 months)
Safety Issue:
Description:
Measure:Percentage of Participants With Abnormal Vital Signs, Electrocardiograms (ECGs) and Eastern Cooperative Oncology Group (ECOG) Performance Status
Time Frame:Baseline up to 30 days after the last dose of study treatment (approximately 10.5 months)
Safety Issue:
Description:Percentage of participants with abnormalities in Systolic blood pressure, diastolic blood pressure, pulse rate, respiratory rate, body temperature as a part of vital signs; electrocardiogram (ECG) wave and Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) will be assessed.
Measure:Objective Response According to RECIST 1.1 assessed by Investigator
Time Frame:Every 6 weeks following the Cycle 1 Day 1 visit until 9 months; every 12 weeks thereafter until disease progression, death, study withdrawal, or withdrawal of consent (each Cycle is of 21 days) (approximately 21.7 months)
Safety Issue:
Description:Participants are identified as having an objective response if they achieve either a confirmed CR or PR from first administration of study treatment to first observation of PD according to RECIST 1.1 as adjudicated by the Investigator. CR: CR defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started.
Measure:Confirmed Complete Response assessed by Independent Review Committee and by Investigator
Time Frame:Every 6 weeks following the Cycle 1 Day 1 visit until 9 months; every 12 weeks thereafter until disease progression, death, study withdrawal, or withdrawal of consent (each Cycle is of 21 days) (approximately 21.7 months)
Safety Issue:
Description:Complete Response (CR) defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non target) must have reduction in short axis to < 10 mm. Participants will be assessed who have confirmed CR if they achieve a confirmed CR from first administration of study treatment to first observation of PD. Participants are identified as having a confirmed CR if they achieve a confirmed CR from first administration of study treatment to first observation of PD.
Measure:Duration of Response assessed by Independent Review Committee and by Investigator
Time Frame:Approximately 21.7 months
Safety Issue:
Description:Duration of response is the time from when the CR/PR (whichever is first) criteria are first met until PD or death due to any cause of the last tumor assessment, whichever occurs first.
Measure:Percentage of Participants With Disease Control as assessed by Independent Review Committee and by Investigator
Time Frame:Approximately 21.7 months
Safety Issue:
Description:Participants are identified as having objective disease control if they achieve either a confirmed CR or PR (confirmation needs to take place after the tumor assessments initially indicating CR or PR), or stable disease (SD).
Measure:Progression-Free Survival Based on Tumor Assessment by the Independent Review Committee and Investigator According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria
Time Frame:Approximately 21.7 months
Safety Issue:
Description:Progression free survival is defined as the time (in months) from first administration of study treatment to the date of the first documentation of PD or death due to any cause of the last tumor assessment, whichever occurs first.
Measure:Overall Survival
Time Frame:Approximately 21.7 months
Safety Issue:
Description:Overall survival is defined as the time (in months) from first administration of study treatment to the date of death.
Measure:Health-Related Quality of Life as Assessed by EuroQol Five Dimension Five Level (EQ-5D-5L) Scale Score
Time Frame:Approximately 21.7 months
Safety Issue:
Description:
Measure:Health-Related Quality of Life as assessed by European Organisation For Research And Treatment of Cancer Quality of Life Questionnaire Core 3D (EORTC-QLQ-C30)
Time Frame:Every 6 weeks following the Cycle 1 Day 1 visit until 9 months; every 12 weeks thereafter until disease progression, death, study withdrawal, or withdrawal of consent (each Cycle is of 21 days) (approximately 21.7 months)
Safety Issue:
Description:
Measure:Health-Related Quality of Life as assessed by Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ)
Time Frame:Every 6 weeks following the Cycle 1 Day 1 visit until 9 months; every 12 weeks thereafter until disease progression, death, study withdrawal, or withdrawal of consent (each Cycle is of 21 days) (approximately 21.7 months)
Safety Issue:
Description:
Measure:Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Tepotinib and Osimertinib
Time Frame:Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after tepotinib and Osimertinib administration at Day 1 of Cycle 1 and Day 15 of Cycle 1 (each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Maximum Observed Plasma Concentration (Cmax) of Tepotinib and Osimertinib
Time Frame:Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after tepotinib and Osimertinib administration at Day 1 of Cycle 1 and Day 15 of Cycle 1 (each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Time to Reach Maximum Observed Plasma Concentration (tmax) of Tepotinib and Osimertinib
Time Frame:Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after tepotinib and Osimertinib administration at Day 1 of Cycle 1 and Day 15 of Cycle 1 (each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Apparent Total Body Clearance (CL/f) of Tepotinib and Osimertinib
Time Frame:Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after tepotinib and Osimertinib administration at Day 1 of Cycle 1 and Day 15 of Cycle 1 (each Cycle is of 21 days)
Safety Issue:
Description:The apparent total body clearance of study intervention following extravascular administration, taking into account the fraction of dose absorbed. CL/f = Dose p.o. /AUC0-infinity (AUC0-inf).
Measure:Apparent Volume Of Distribution (Vz/F) of Tepotinib and Osimertinib
Time Frame:Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after tepotinib and Osimertinib administration at Day 1 of Cycle 1 and Day 15 of Cycle 1 (each Cycle is of 21 days)
Safety Issue:
Description:The apparent volume of distribution during the terminal phase following extravascular administration, based on the fraction of dose absorbed. The Vz/f was calculated by dividing the dose with area under the concentration time curve from time zero to infinity multiplied with terminal elimination rate constant Lambda(z). Vz/f=Dose/AUC(0-inf)* Lambda(z).
Measure:Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Mutation
Time Frame:From Day 1 of Cycle 3 up to end of treatment (14 days after last dose) (each Cycle is for 21 days) (approximately 7.5 months)
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:EMD Serono Research & Development Institute, Inc.

Trial Keywords

  • Tepotinib
  • Osimertinib
  • Non-Small Cell Lung Cancer
  • INSIGHT 2

Last Updated