List of Cleared or Approved Companion Diagnostic Devices (In Vitro and Imaging Tools)

For in vitro diagnostic use.

The FoundationFocus™ CDxBRCA is a next generation sequencing based in vitro diagnostic device for qualitative detection of BRCA1 and BRCA2 alterations in formalin-fixed paraffin-embedded (FFPE) ovarian tumor tissue. The FoundationFocus CDxBRCA assay detects sequence alterations in BRCA1 and BRCA2 (BRCA1/2) genes. Results of the assay are used as an aid in identifying ovarian cancer patients for whom treatment with Rubraca™ (rucaparib) is being considered. If a patient is positive for any of the deleterious alterations specified in the BRCA1/2 classification, the patient may be eligible for treatment with Rubraca. This assay is to be performed at Foundation Medicine, Inc., a single laboratory site located at 150 Second Street, Cambridge, MA 02141.

For in vitro diagnostic use.

PD-L1 IHC 22C3 pharmDx is a qualitative immunohistochemical assay using Monoclonal Mouse Anti-PD-L1, Clone 22C3 intended for use in the detection of PD-L1 protein in formalin-fixed, paraffin-embedded (FFPE) non-small cell lung cancer (NSCLC) tissue using EnVision FLEX visualization system on Autostainer Link 48. PD-L1 protein expression is determined by using Tumor Proportion Score (TPS), which is the percentage of viable tumor cells showing partial or complete membrane staining at any intensity. The specimen should be considered to have PD-L1 expression if TPS ≥ 1% and high PD-L1 expression if TPS ≥ 50%.

PD-L1 IHC 22C3 pharmDx is indicated as an aid in identifying NSCLC patients for treatment with KEYTRUDA® (pembrolizumab). See the KEYTRUDA® product label for expression cutoff values guiding therapy in specific clinical circumstances.

The cobas® EGFR Mutation Test v2 is a real-time PCR test for the qualitative detection of defined mutations of the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC) patients. Defined EGFR mutations are detected using DNA isolated from formalin-fixed paraffin-embedded tumor tissue (FFPET) or circulating-free tumor DNA (cfDNA) from plasma derived from EDTA anti-coagulated peripheral whole blood.

The test is indicated as a companion diagnostic to aid in selecting NSCLC patients for treatment with the targeted therapies listed in Table 1 below in accordance with the approved therapeutic product labeling.

Patients with positive cobas® EGFR Mutation Test v2 test results using plasma specimens for the presence of the EGFR mutations listed above are eligible for treatment with the corresponding drug as indicated in Table 1 (see Note* for T790M). Patients who are negative for these mutations by this test should be reflexed to routine biopsy and testing for EGFR mutations with the FFPET sample type.

*The efficacy of TAGRISSO™ (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for T790M plasma-positive patients are limited; therefore testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy cannot be obtained.

Drug safety and efficacy have not been established for the EGFR mutations listed in Table 2 below that are also detected by the cobas® EGFR Mutation Test v2.

For manual sample preparation, FFPET specimens are processed using the cobas® DNA Sample Preparation Kit and plasma specimens are processed using the cobas® cfDNA Sample Preparation Kit. The cobas z 480 analyzer is used for automated amplification and detection.

The cobas® EGFR Mutation Test v2 is a real-time PCR test for the qualitative detection of defined mutations of the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC) patients. Defined EGFR mutations are detected using DNA isolated from formalin-fixed paraffin-embedded tumor tissue (FFPET) or circulating-free tumor DNA (cfDNA) from plasma derived from EDTA anti-coagulated peripheral whole blood.

The test is indicated as a companion diagnostic to aid in selecting NSCLC patients for treatment with the targeted therapies listed in Table 1 below in accordance with the approved therapeutic product labeling.

Patients with positive cobas® EGFR Mutation Test v2 test results using plasma specimens for the presence of EGFR exon 19 deletions or L858R mutations are eligible for treatment with TARCEVA® (erlotinib). Patients who are negative for these mutations by this test should be reflexed to routine biopsy and testing for EGFR mutations with the FFPET sample type.

Drug safety and efficacy have not been established for the EGFR mutations listed in Table 2 below that are also detected by the cobas® EGFR Mutation Test v2.

For manual sample preparation, FFPET specimens are processed using the cobas® DNA Sample Preparation Kit and plasma specimens are processed using the cobas® cfDNA Sample Preparation Kit. The cobas z 480 analyzer is used for automated amplification and detection.

The Vysis CLL FISH Probe Kit is a test to detect deletion of the LSI TP53 probe target via fluorescence in situ hybridization (FISH) in peripheral blood specimens from patients with B-cell chronic lymphocytic leukemia (CLL).

The test is indicated for detecting deletion of the LSI TP53 probe target (17p-) as an aid in identifying those patients with CLL for whom treatment with VENCLEXTA® (venetoclax) is indicated. Vysis CLL FISH Probe Kit is not intended for monitoring of residual disease.

KIT D816V Mutation Detection by PCR for Gleevec Eligibility in Aggressive Systemic Mastocytosis (ASM) (referred to as the "KIT D816V assay") is an in vitro diagnostic test intended for qualitative polymerase chain reaction (PCR) detection of KIT D816V mutational status from fresh bone marrow samples of patients with aggressive systemic mastocytosis. The KIT D816V mutational assay is indicated as an aid in the selection of ASM patients for whom Gleevec® (imatinib mesylate) treatment is being considered. This assay is for professional use only and is to be performed at a single laboratory site.

The indication for use statement has been modified from that granted for the HUD designation. The HUD designation was for use in skin or bone marrow biopsies. It was modified for the HDE approval to limit the assay use to fresh bone marrow biopsies.

The PDGFRB FISH for Gleevec Eligibility in Myelodysplastic Syndrome/ Myeloproliferative Disease (MDS/MPD) is an in vitro diagnostic test intended for the qualitative detection of PDGFRB gene rearrangement from fresh bone marrow samples of patients with MDS/MPD with a high index of suspicion based on karyotyping showing a 5q31~33 anomaly. The PDGFRB FISH assay is indicated as an aid in the selection of MDS/MPD patients for whom Gleevec®(imatinib mesylate) treatment is being considered. This assay is for professional use only and is to be performed at a single laboratory site.

The indication for use statement has been modified from that granted for the HUD designation. The HUD designation was for use in both peripheral blood and bone marrow specimens. It was modified for the HDE approval to indicate that only fresh bone marrow samples may be used.

The cobas® EGFR Mutation Test v2 is a real-time PCR test for the qualitative detection of defined mutations of the epidermal growth factor receptor (EGFR) gene in DNA derived from formalin-fixed paraffin-embedded tumor tissue (FFPET) from non-small cell lung cancer (NSCLC) patients. The test is intended to aid in identifying patients with NSCLC whose tumors have defined EGFR mutations and for whom safety and efficacy of a drug have been established as follows:

• Tarceva® (erlotinib) - Exon 19 deletions and L858R
• Tagrisso® (osimertinib) - T790M

Drug safety and efficacy have not been established for the following EGFR mutations also detected by the cobas® EGFR Mutation Test v2:

• Tarceva® (erlotinib) - G719X, exon 20 insertions, T790M, S768I and L861Q
• Tagrisso® (osimertinib) - G719X, exon 19 deletions, L858R, exon 20 insertions, S768I, and L861Q

For manual sample preparation, FFPET specimens are processed using the cobas® DNA Sample Preparation Kit and the cobas z 480 analyzer is used for automated amplification and detection.

PD-L1 IHC 22C3 pharmDx is a qualitative immunohistochemical assay using Monoclonal Mouse Anti-PD-L1, Clone 22C3 intended for use in the detection of PD-L1 protein in formalin-fixed, paraffin-embedded (FFPE) non-small cell lung cancer (NSCLC) tissue using EnVision FLEX visualization system on Autostainer Link 48. PD-L1 protein expression is determined by using Tumor Proportion Score (TPS), which is the percentage of viable tumor cells showing partial or complete membrane staining. The specimen should be considered PD-L1 positive if TPS ≥ 50% of the viable tumor cells exhibit membrane staining at any intensity.

PD-L1 IHC 22C3 pharmDx is indicated as an aid in identifying NSCLC patients for treatment with KEYTRUDA® (pembrolizumab).

The therascreen® EGFR RGQ PCR Kit is a real-time PCR test for the qualitative detection of exon 19 deletions and exon 21 (L858R) substitution mutations of the epidermal growth factor receptor (EGFR) gene in DNA derived from formalin-fixed paraffin-embedded (FFPE) non-small cell lung cancer (NSCLC) tumor tissue. The test is intended to be used to select patients with NSCLC for whom GILOTRIF® (afatinib) or IRESSA® (gefitinib), EGFR tyrosine kinase inhibitors (TKIs), is indicated. Safety and efficacy of GILOTRIF (afatinib) and IRESSA (gefitinib) have not been established in the patients whose tumors have L861Q, G719X, S768I, exon 20 insertions, and T790M mutations, which are also detected by the therascreen EGFR RGQ PCR Kit.

Specimens are processed using the QIAamp® DSP DNA FFPE Tissue Kit for manual sample preparation and the Rotor-Gene Q MDx instrument for automated amplification and detection.