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MASTER KEY プロジェクト > プロジェクトについて > MASTER KEY Project Overview

MASTER KEY Project Overview

NCC projects for genome-based drug discovery

 図1

TOP GEARProject(Relevant project of MASTER KEY)

TOP-GEAR Project(Trial of Onco-Panel for Gene-profiling to Estimate both Adverse events and Response by cancer treatment)

Since 2013 (Clinical trial registry: UMIN000011141)

図2

  1. Treatment choice (including a clinical trial)
  2. Prediction of the effect of biomarker-based treatment
  3. Prediction of the effect of immune checkpoint inhibitor
  4. Diagnosis of cancer type
  5. Prediction of prognosis
  6. Specification of origin of cancer of unknown primary
  7. Diagnosis of recurrence
  8. Diagnosis of multiple cancer
  9. Treatment choice for drug resistance

Designated as the “sakigake” scheme item in Feb 2017

TOP GEAR: NCCOncopanelver4.0

 図3

TOP GEAR PROJECTNCC in-house clinical sequencing program

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  • 1st period (2013-)
    • Evaluate clinical utility
    • Clinical sequencing at a research institute
    • Results fed back to doctors
    • Some patients enrolled into phase I studies
  • 2nd period (2016-)
    • Evaluate feasibility in clinical practice
    • Clinical sequencing at a quality-assured lab
    • Results fed back to patients and doctors
    • Customized multiple gene panel (NCC Oncopanel)
  • 3rd period (2018-)
    • Clinical trial aiming at national health insurance reimbursement for NCC Oncopanel

Cancer multi-gene panel program(NCC Oncopanel)

図5

Actionable alterations &matched treatment

図6

TOP GEAR: Cancer types (n=207)

 図7

Clinical trial to obtain national health insurance reimbursement for NCC Oncopanel

図8

 MASTER KEY Project Overview

MASTER KEY Project

MASTER_KEY_Project.JPG

Why rare cancer?

  • Delayed treatment development
    • Difficult to conduct a randomized trial due to limited number of patients
    • Industries are rarely interested in such a small market
    • Molecular background is not well investigated
    • Few hospitals with sufficient function for precise diagnosis and treatment
  • Rare cancer is not so rare
    • The annual incidence of all rare cancer occupies 15% of all cancer diagnosis in Japan

図10

Rare Cancer Center in NCC (since 2014)

図13

NCC Rare Cancer Hotline

図11

MASTER KEY Project

 MASTER_KEY_Project_Registry_Part.JPG

Registry part

  • Aim
    • Comprehensive database for rare cancer
         Molecular background, natural history, treatment outcomes, etc
    • Use the data for applications for regulatory approval
         Reliable historical control data
    • Assignment to clinical trials
         -Biomarker-targeted and non-biomarker-targeted clinical trials
         -If no clinical trial is available patients will receive treatment options outside of clinical trials
  • Collaboration with industries
    • Joint project with 12 industries
      • Funding, study drugs
      • Industry-sponsored sub-study
  • Accrual target
    • >= 200 patients/year

Registry part: Eligibility Criteria

Main inclusion criteria

Main_inclusion_criteria.png

Registry Part: Progress

Opened in May 2017

  • Expected accrual rate: 200 patients per year
  • Study period: 5 years and more (continuous development)

Progress as of October 2021

  • Accrual: more than 2000 patients
  • Interim study reports: every six months

MASTER KEY Project

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Sub-study (Clinical trial part)

図16
  • Several sub-studies are conducted as a basket trial
    • Marker(+): BRAF-V600, ALK, MDM2, HER2 etc.
    • Marker(-): Immune checkpoint inhibitors, etc
  • Aim
    • to expand drug indication to rare cancer Typical sub-study design
  • Single-arm phase 2
    • Primary endpoint, response rate
    • 15-25 patients with bayesiandesign

Sub-study

 Sub-study_Progress.jpg

Collaboration between industries and academia

MASTER_KEY_Collaboration_between_industries_and_academia.JPG

Collaborating institutions

  • National Cancer Center Hospital
  • Kyoto University Hospital (Joined August 2018)
  • Hokkaido University Hospital (Joined April 2019)
  • Kyushu University Hospital (Joined April 2019)
  • Tohoku University Hospital (Joined February 2020)

Collaborating industries

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Collaboration with 12 industries

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Advantages for academia

  • Obtain stable funding from industries for the registry
  • Obtain investigational drug/funding for investigator-initiated sub-studies
  • Propose industry-sponsored sub-studies for the registered patients

Advantages for industries

  • Obtain interim study reports periodically
  • Request detailed analysis of the registry data
  • Utilize the registry data as a reliable historical control for industry-sponsored trials
  • Accelerate the patient accrual for the industry-sponsored sub-studies

Summary: MASTER KEY Project

MASTER KEY Registry

  • Collaboration with 12 industries and 5 institutions
  • Started since May 2017
  • More than 200 patients/year
  • Accrual: more than 2000 patients

MASTER KEY Sub-study

  • 19 trials are being conducted
  • Collaboration with industries