Lung Cancer Compact Panel® Dx
Multi-Companion Diagnostic System
on the approved use of the Lung Cancer Compact Panel® Dx
Multi-companion Diagnostic System in Japan
Multi-Companion Diagnostic System
(NGS) to detect multiple driver gene alterations in specimens from patients with NSCLC (non-small cell lung cancer)
correspond to alterations in eight driver genes and are approved by the Japanese
regulatory authorities under the Pharmaceuticals and Medical Devices Act.
and three other driver genes for research use only.
5% or greater.
drugs and their corresponding genetic alterations. CDx, the target drug, and the relevant
genetic alteration are therefore linked within the regulatory approval framework.
Approved Product Information in Japan
| Product Name | Lung Cancer Compact Panel® Dx Multi-companion Diagnostic System |
| Generic Name |
Somatic Gene Mutation Analysis Program
(for Antineoplastic Drug Eligibility Assessment) |
| JMDN＊ Code | 70159013 |
| Classification of Medical Device | Class Ⅲ |
| Approval Number | 30400BZX00263000 |
| Approval Date | November 16, 2022 |
| Partial Change Approval Date | Partial Change Approval Date |
| Marketing Start Date | Marketing Start Date |
Feature
Feature 1:Comprehensive detection of key lung cancer genes
covered by the approval
detection of epidermal growth factor receptor(
EGFR
)mutations (including exon 20
insertion),
ALK
fusion,
ROS1
fusion,
MET
exon 14 skipping mutations,
KRAS
G12C,
BRAF
V600E,
RET
fusion,and
HER2
/
ERBB2
mutation
Target driver gene alterations and associated therapies:
Approved companion diagnostic (CDx) targets in Japan
| CDx | Target | Associated Drugs | |||||
|---|---|---|---|---|---|---|---|
| CDx |
EGFR
mutations
(except exon20 insertion) |
Molecularly targeted drugs for
EGFR
|
|||||
| CDx | EGFR exon20 insertion | Amivantamab | |||||
| CDx | ALK fusions | Alectinib | |||||
| Crizotinib | |||||||
| Brigatinib | |||||||
| Lorlatinib | |||||||
| CDx | ROS1 fusions | Crizotinib | |||||
| CDx | MET exon14 skipping | Tepotinib | |||||
| CDx | KRAS G12C | Sotorasib | |||||
| CDx | BRAF V600E |
Dabrafenib
Trametinib |
|||||
| CDx | RET fusions | Selpercatinib | |||||
| CDx | HER2 ( ERBB2 ) mutations | Trastuzumab Deruxtecan |
Research-use reportable genes (non-CDx targets in Japan)
| Measurement Target | |
|---|---|
| HER2/ERBB2 mutations non-CDx variants | NTRK1 fusions |
| NRG1 mutations | NTRK2 fusions |
| LTK mutations | NTRK3 fusions |
| ALK mutations non-CDx variants | BRAF mutations non-CDx variants |
| KRAS mutations non-CDx variants | EGFR mutations (DNA variants) |
| MET fusions non-CDx variants | RET fusions non-CDx variants |
| ROS1 fusions non-CDx variants | ー |
diagnostics (CDx) by the Japanese regulatory authorities under the Pharmaceuticals and
Medical Devices Act
Feature 2: High Detection Sensitivity (1%)
A detection sensitivity of 1% was achieved by limiting the number of target genes,
partitioning them into smaller modules, and conducting high-depth sequencing.
By prioritizing the sequencing of clinically-relevant genetic alterations, the assay can detect
mutations even when only a small proportion of mutant DNA is present in the sample.
Analytical performance studies have demonstrated the ability to reliably discriminate
between samples with variant allele frequencies of 0% and 1% as negative and positive,
respectively, indicating a low incidence of false-positives and false-negatives.
Note:
Variant Allele Fraction (VAF) = Number of mutant DNA molecules ÷ (number of normal cell-derived DNA molecules +
number of tumor-derived DNA molecules)
Feature 3: Compatibility with cytology samples
Applicability to formalin-fixed paraffin-embedded slides and cytology specimens from
transbronchial biopsy and transbronchial needle aspiration: The validation showed a 100%
success rate and a 98.7% positive concordance.
Feature 4: Expandable modular design
As new driver mutations are discovered, the range of detectable genetic alterations may
need to be expanded.
To address this, the assay uses a modular design that enables the
addition of new modules (reaction units) independently of existing validated modules.This
approach facilitates the incorporation of new targets without compromising the analytical
performance of the variants already covered by the assay.
Feature 5: The first lung cancer gene panel developed in Japan
Developed from research conducted at the Nara Institute of Science and Technology and
Osaka International Cancer Institute
Eligible Specimens and Required Nucleic Acid Amount
Eligible Specimens
| Specimen | Amount | Tumor Fraction | Storage |
|---|---|---|---|
|
FFPE unstained
slides |
Surgical: 4–5 μm × 2–5 slides,
approx. 8 mm² |
≥5%
recommended |
Room temperature |
|
Biopsy: 4–5 μm × 5–10 slides,
≥4 mm² |
|||
|
Small biopsy: 4–5 μm × 15–20 slides,
≤4 mm² |
|||
| Cytology | 1 mg (1 mm cube) |
Recommended
refrigerated (Gene Metrics tube) * |
Recommended
frozen as cytology pellet |
| Unfixed tissue | 1 mg (1 mm cube) |
Recommended
frozen |
preservation container designed for long-term storage of nucleic acids at room temperature
or refrigerated conditions
* GM Tube (Genemetrics nucleic acid preservation solution container; Genemetrics LLC,
Osaka, Japan): A specimen preservation tube developed for the long-term stable storage of
nucleic acids in tissue samples at room temperature or under refrigerated conditions.
Required Nucleic Acid Amount
| Nucleic acids | Required Amount |
|---|---|
| DNA | ＞ 10ng | RNA | ＞ 10ng |
Important Requirements for Testing
- ◆Recommended tumor fraction: 5% or greater
- ◆Recommended tumor fraction: 5% or greater
- ◆Insufficient specimen volume may result in test failure
-
◆Based on the limit of detection of 1% variant allele frequency, a tumor fraction of at least
2% is required. Lower tumor fractions may increase the risk of false-negative results.
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“Compact Panel®” is available within Japan.
