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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)

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ClinicalTrials.gov Identifier: NCT03940703
Recruitment Status : Not yet recruiting
First Posted : May 7, 2019
Last Update Posted : July 8, 2019
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Tracking Information
First Submitted Date  ICMJE May 6, 2019
First Posted Date  ICMJE May 7, 2019
Last Update Posted Date July 8, 2019
Estimated Study Start Date  ICMJE July 18, 2019
Estimated Primary Completion Date March 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 6, 2019)
  • 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) ]
  • Objective response determined according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as per Independent Review Committee (IRC) [ 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) ]
    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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03940703 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2019)
  • 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) ]
  • 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) ]
  • 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) ]
    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.
  • 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) ]
    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.
  • 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) ]
    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.
  • Duration of Response assessed by Independent Review Committee and by Investigator [ Time Frame: Approximately 21.7 months ]
    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.
  • Percentage of Participants With Disease Control as assessed by Independent Review Committee and by Investigator [ Time Frame: Approximately 21.7 months ]
    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).
  • 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 ]
    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.
  • Overall Survival [ Time Frame: Approximately 21.7 months ]
    Overall survival is defined as the time (in months) from first administration of study treatment to the date of death.
  • Health-Related Quality of Life as Assessed by EuroQol Five Dimension Five Level (EQ-5D-5L) Scale Score [ Time Frame: Approximately 21.7 months ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
    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).
  • 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) ]
    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).
  • 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) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Tepotinib
    Participants will be administered Tepotinib at an initial dose of 500 milligram (mg). A safety monitoring committee (SMC) may decide to confirm or adapt the dose.
  • Drug: Osimertinib
    Participants will receive Osimertinib at a dose of 80 mg orally once daily.
    Other Name: Tagrisso®
Study Arms  ICMJE Experimental: Tepotinib and Osimertinib
Participants 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.
Interventions:
  • Drug: Tepotinib
  • Drug: Osimertinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: May 6, 2019)
90
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 30, 2022
Estimated Primary Completion Date March 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: US Medical Information 888-275-7376 service@emdgroup.com
Contact: Communication Center +49 6151 72 5200 service@emdgroup.com
Listed Location Countries  ICMJE Germany,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03940703
Other Study ID Numbers  ICMJE MS200095_0031
2019-001538-33 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, EMD Serono will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be is found on our website https://www.emdgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html
Responsible Party EMD Serono ( EMD Serono Research & Development Institute, Inc. )
Study Sponsor  ICMJE EMD Serono Research & Development Institute, Inc.
Collaborators  ICMJE Merck KGaA, Darmstadt, Germany
Investigators  ICMJE
Study Director: Medical Responsible Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany
PRS Account EMD Serono
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP