BEUDAMED
    FDA Adverse Event Malfunction Summary report: N

    ONCOMINE DX TARGET TEST ASSAY DEFINITION FILE

    MDR report key: 16161190 · Received January 13, 2023

    Report

    Report Number
    3003335080-2023-00001
    Event Type
    Malfunction
    Date Received
    January 13, 2023
    Date of Event
    December 13, 2022
    Report Date
    January 13, 2023
    Manufacturer
    LIFE TECHNOLOGIES CORPORATION
    Product Code
    PQP
    PMA / PMN Number
    P160045
    Product Problem
    Yes
    Report Source
    Manufacturer report
    Reporter Location
    CA, US
    Reporter Occupation
    003

    Narratives

    Additional Manufacturer Narrative · 0

    THE RAW DATA FROM REM-01-068 WAS REVIEWED THROUGH ALTERNATIVE ANALYSIS METHODS AND R&D DISCOVERED A COSM12553 SEQUENCE WAS PRESENT BUT THERE WAS ALSO AN ADJACENT SNV IN THE EVALUATION WINDOW WHICH MAKES THIS A RARE COMPLEX VARIANT THAT WAS NOT ENCOUNTERED DURING OUR ORIGINAL CLINICAL STUDY FOR DAICHI'S ENHERTU US APPROVAL. THE ANALYSIS SHOWED THE FOLLOWING: TG---GTGTGGG REF , TGTGTGTGTGGG COSM12553 DISCOVERED [THIS IS WITHIN OUR HOTSPOT FILE], AGTGTGTGTGGG COMPLEX (T>A SYNONYMOUS SNV+ COSM12553). THE ODXT TEST ADF ONLY PERFORMS HOTSPOT CALLING. THE COSM12553+SNV COMPLEX ALLELE DISCOVERED IS NOT IN THE HOTSPOT BED FILE OF THE VARIANT CALLER AND THEREFORE DOES NOT CALL THIS COMPLEX ALLELE. THE FOLLOW LIMITATION IS PRESENT IN USER GUIDE ((B)(4), REV B) AND APPROVED UNDER (B)(4). THIS REVISION WILL BE COMMERCIALIZED IN JAN 2023. FOR NSCLC, THE ONCOMINE¿ DX TARGET TEST ASSAY DEFINITION FILE INCLUDES PREVALENT BUT NOT ALL RARE OR NEWLY IDENTIFIED RET ISOFORMS, ROS1 ISOFORMS, EGFR EXON 20 INSERTIONS, AND ERBB2/HER2 ACTIVATING MUTATIONS. THE ONCOMINE¿ DX TARGET TEST MAY MISS RARE OR NEWLY IDENTIFIED: RET ISOFORMS CARRIED BY A SUBSET OF PATIENTS WHO MAY DERIVE BENEFIT FROM PRALSETINIB, ROS1 ISOFORMS CARRIED BY A SUBSET OF PATIENTS WHO MAY DERIVE BENEFIT FROM CRIZOTINIB, EGFR EXON 20 INSERTIONS CARRIED BY A SUBSET OF PATIENTS WHO MAY DERIVE BENEFIT FROM MOBOCERTINIB OR AMIVANTAMAB-VMJW, ERBB2/HER2 ACTIVATING MUTATIONS CARRIED BY A SUBSET OF PATIENTS WHO MAY DERIVE BENEFIT FROM FAM-TRASTUZUMAB DERUXTECAN-NXKI. ONLY PATIENTS THAT HAVE BOTH COSM12553 AND AN ADDITIONAL ADJACENT SNV WILL BE IMPACTED BY THIS LIMITATION. THIS IS A RARE OCCURRENCE. EXACT PREVALENCE IS UNKNOWN BUT 0 RESULTS WERE FOUND IN A SEARCH OF DBSNP AND GNOMAD FOR THE SYNONYMOUS SNP DETECTED IN THIS CASE.

    Description of Event or Problem · 0

    THE ONCOMINE¿ DX TARGET TEST IS A QUALITATIVE IN VITRO DIAGNOSTIC TEST THAT USES TARGETED HIGH-THROUGHPUT, PARALLEL-SEQUENCING TECHNOLOGY TO DETECT SINGLE NUCLEOTIDE VARIANTS (SNVS), INSERTIONS, AND DELETIONS IN 23 GENES FROM DNA AND FUSIONS IN ROS1 AND RET FROM RNA ISOLATED FROM FORMALIN-FIX ED, PARAFFIN-EMBEDDED (FFPE) TUMOR TISSUE SAMPLES FROM PATIENTS WITH NON-SMALL CELL LUNG CANCER (NSCLC), AND IDH1 SNVS FROM FFPE TUMOR TISSUE SAMPLES FROM PATIENTS WITH CHOLANGIOCARCINOMA (CC) USING THE ION PGM¿ DX SYSTEM. THIS TEST ALSO INCLUDES CDX CLAIMS FOR THE FOLLOWING: THE TEST IS INDICATED AS A COMPANION DIAGNOSTIC TO AID IN SELECTING NSCLC AND CC PATIENTS FOR TREATMENT WITH THE TARGETED THERAPIES LISTED IN TABLE 1 IN ACCORDANCE WITH THE APPROVED THERAPEUTIC PRODUCT LABELING. TABLE 1: LIST OF VARIANTS FOR THERAPEUTIC USE TISSUE TYPE GENE VARIANT TARGETED THERAPY NSCLC BRAF BRAF V600E MUTATIONS TAFINLAR® (DABRAFENIB) IN COMBINATION WITH MEKINIST® (TRAMETINIB) EGFR EGFR L858R MUTATION, EGFR EXON 19 DELETIONS IRESSA® (GEFITINIB) EGFR EGFR EXON 20 INSERTIONS EXKIVITY¿ (MOBOCERTINIB) RYBREVANT¿ (AMIVANTAMAB-VMJW) ROS1 ROS1 FUSIONS XALKORI® (CRIZOTINIB) ERBB2/HER2 ERBB2/HER2 ACTIVATING MUTATIONS*(SNVS AND EXON 20 INSERTIONS) ENHERTU® (FAM-TRASTUZUMAB DERUXTECAN-NXKI) RET FUSIONS GAVRETO¿ (PRALSETINIB) ROS1 ROS1 FUSIONS XALKORI® (CRIZOTINIB) CC IDH1 R132C, IDH1 R132G, IDH1 R132H, IDH1 R132L, AND IDH1 R132S TIBSOVO® (IVOSIDENIB) SAFE AND EFFECTIVE USE HAS NOT BEEN ESTABLISHED FOR SELECTING THERAPIES USING THIS DEVICE FOR THE VARIANTS OTHER THAN THOSE LISTED IN TABLE 1. RESULTS OTHER THAN THOSE LISTED IN TABLE 1 ARE INDICATED FOR USE ONLY IN PATIENTS WHO HAVE ALREADY BEEN CONSIDERED FOR ALL APPROPRIATE THERAPIES (INCLUDING THOSE LISTED IN TABLE 1). ANALYTICAL PERFORMANCE USING NSCLC SPECIMENS HAS BEEN ESTABLISHED FOR THE VARIANTS LISTED IN TABLE 2. TABLE 2. LIST OF VARIANTS WITH ESTABLISHED ANALYTICAL PERFORMANCE ONLY GENE VARIANT ID AMINO ACID CHANGE NUCLEOTIDE CHANGE KRAS COSM512 P.GLY12PHE C.34_35DELGGINSTT KRAS COSM516 P.GLY12CYS C.34G>T MET COSM707 P.THR1010ILE C.3029C>T PIK3CA COSM754 P.ASN345LYS C.1035T>A THE TEST IS NOT INDICATED TO BE USED FOR STANDALONE DIAGNOSTIC PURPOSES, SCREENING, MONITORING, RISK ASSESSMENT, OR PROGNOSIS. RECENTLY, THE ODXT TEST WAS USED RETROSPECTIVELY AS PART OF AN EX-US VALIDATION STUDY FOR USE AS A CDX. A BANKED SAMPLE FROM A CDX STUDY WAS CALLED NEGATIVE FOR A RARE ERBB2 COMPLEX MUTATION WHEN ORTHOGONAL TESTING CALLED THE SAMPLE POSITIVE FOR COSM12553. THIS SCENARIO WAS NOT DISCOVERED BY A CUSTOMER. ODXT TEST RESULTS WERE NOT USED FOR PATIENT ENROLLMENT AND RESULTS WERE NOT REPORTED TO ANY PHYSICIAN OR PATIENT. IN THE WRITTEN FEEDBACK TO Q SUB (B)(6) , FDA REQUESTED ANY DE NOVO VARIANTS THAT WE OR OUR CUSTOMERS FIND SHOULD BE REPORTED VIA A MEDICAL DEVICE REPORT (MDR) AND VIA EMAIL TO FDA.

    Devices

    Seq Brand Generic Product Code Manufacturer Model Lot UDI-DI
    1529411 ONCOMINE DX TARGET TEST ASSAY DEFINITION FILE NEXT GENERATION SEQUENCING ONCOLOGY PANEL, SOMATIC OR GERMLINE VARIANT DETECTION PQP LIFE TECHNOLOGIES CORPORATION

    Patients

    Seq Age Sex Outcome Treatment
    1 Unknown