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MASTER KEY プロジェクト

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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)

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Actionable alterations &matched treatment

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TOP GEAR: Cancer types (n=207)

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Clinical trial to obtain national health insurance reimbursement for NCC Oncopanel

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 MASTER KEY Project Overview

MASTER KEY PROJECT

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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

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Rare Cancer Center in NCC (since 2014)

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NCC Rare Cancer Hotline

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MASTER KEY PROJECT

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Registry part

  • Aim
    • Comprehensive database for rare cancer
      • Establish reliable historical control data
    • Assignment to mutation-based basket trials
      • Some trials target marker-negative patients
  • Collaboration with industries
    • Joint project with 11 industries
      • Funding, study drugs
      • Industry-sponsored sub-study
  • Accrual target
    • >= 200 patients/year

Registry part: Eligibility Criteria

Main inclusion criteria

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Registry Part: Progress

Opened in May 2017

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

Progress as of October 2018

  • Accrual: more than 300 patients
  • Pediatric cancers: since April 2018z
  • Hematologic malignancies: since Oct 2018
  • Interim study reports: every six months

Preparation for new collaborating institutions

  • Kyoto University Hospital (Joined April 2018)
  • Other institutions (from Hokkaido area and Kyushu area) in negotiation

MASTER KEY PROJECT

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Sub-study

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  • 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: Progress

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MASTER KEY: Collaboration between industries and academia

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MASTER KEY: Collaboration with 11 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

TOP-GEAR/NCC Oncopanel

  • NCC has developed quality-assured clinical sequence program
  • Clinical trial aiming at pharmaceutical approval/reimbursement for NCC Oncopanelis ongoing
  • Clinical sequence will be incorporated into clinical practice since next year

MASTER KEY Registry

  • Collaboration with 11 industries
  • Started since May 2017
  • More than 200 patients/year

MASTER KEY Sub-study

  • 12 trials are being conducted or prepared
Collaboration with industries