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
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)
- Treatment choice (including a clinical trial)
- Prediction of the effect of biomarker-based treatment
- Prediction of the effect of immune checkpoint inhibitor
- Diagnosis of cancer type
- Prediction of prognosis
- Specification of origin of cancer of unknown primary
- Diagnosis of recurrence
- Diagnosis of multiple cancer
- Treatment choice for drug resistance
Designated as the “sakigake” scheme item in Feb 2017
TOP GEAR: NCCOncopanelver4.0
TOP GEAR PROJECTNCC in-house clinical sequencing program
- 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)
Actionable alterations &matched treatment
TOP GEAR: Cancer types (n=207)
Clinical trial to obtain national health insurance reimbursement for NCC Oncopanel
MASTER KEY Project Overview
MASTER KEY Project
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
Rare Cancer Center in NCC (since 2014)
NCC Rare Cancer Hotline
MASTER KEY Project
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
- Comprehensive database for rare cancer
- Collaboration with industries
- Joint project with 12 industries
- Funding, study drugs
- Industry-sponsored sub-study
- Joint project with 12 industries
- Accrual target
- >= 200 patients/year
Registry part: Eligibility Criteria
Main inclusion criteria
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
Sub-study (Clinical trial part)
- 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
Collaboration between industries and academia
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
Collaboration with 12 industries
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
