Roche launches first IVD pan-TRK immunohistochemistry assay

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27 Nov, 2018, 12:00 GMT

- The VENTANA pan-TRK (EPR17341) Assay[1] is the first assay of its type to detect tropomyosin receptor kinase (TRK) with anticipated use across multiple solid tumor types

- The assay is expected to provide improved data on the prevalence of TRK proteins in tumor tissue studies

- The significance of TRK fusion proteins is currently being investigated in various cancer indications

TUCSON, Arizona, Nov. 27, 2018 /PRNewswire/ -- Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced the global launch of the VENTANA pan-TRK (EPR17341) Assay, the first automated in vitro diagnostic (IVD) immunohistochemistry (IHC) assay to detect tropomyosin receptor kinase (TRK) proteins in cancer.

With the launch, laboratories are now able to identify wild-type and chimeric fusion proteins through detection of the TRK C-terminal region. This assay can be used to perform analytic studies, including prevalence in solid tumors.

This image opens in the lightbox — Left: Protein expression in mammary analogue secretory carcinoma with TRK fusion stained with VENTANA pan-TRK (EPR17341) Assay (20x)* (*Fusion status based upon next generation sequencing reported from external laboratory developed test using OncomineTM Focus Assay[14-17]) Right: Protein expression in head and neck squamous cell carcinoma with wild-type TRK stained with VENTANA pan-TRK (EPR17341) Assay (20x)

While wild-type protein expression is generally low in both prevalence and intensity level, it can be substantial in some neuroendocrine tumor tissues. TRK-fusion proteins have been identified in a wide range of commonly occurring tumors, including lung, thyroid and sarcoma, at a low frequency.^2-8 In some rare tumors, including infantile fibrosarcoma, secretory and juvenile breast cancer and mammary analogue secretory cancers of the salivary glands, TRK fusion proteins are likely to be the defining genetic feature.^9-13

"As the first test of its kind, the VENTANA pan-TRK (EPR17341) Assay provides an important new tool to help us better understand the role of TRK protein expression, particularly fusions in cancer," said Jill German, Head of Roche Tissue Diagnostics. "We are excited to see the new information that results from the use of this important technology, and its ultimate impact for patients."

The VENTANA pan-TRK (EPR17341) Assay is available for use on Roche's BenchMark series of IHC/ISH automated staining instruments.

About the VENTANA pan-TRK (EPR17341) Assay
The VENTANA pan-TRK (EPR17341) CE IVD/US Class I Assay is designed to detect C-terminal protein expression, which allows for the detection of TRK-fusion as well as wild-type protein expression. The epitope detected by the antibody is encoded downstream of the tyrosine kinase domain within the 3 prime coding region of the neurotrophic tyrosine receptor kinase (NTRK) 1, 2 and 3 genes and is conserved across all three TRK proteins, A, B and C.

NTRK genes are oncogenes that can be activated and drive cancer progression when chromosomal rearrangements lead to their juxtaposition with other genes, including ETV6, EML4, LMNA and TPM3. The resulting TRK-fusion proteins can drive overexpression and constitutive activation of the TRK tyrosine kinase, leading to aberrant signaling through downstream pathways. NTRK gene fusions are currently being explored in clinical trials for several targeted cancer therapies.

About Roche
Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people's lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare – a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the world's largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. Thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the tenth consecutive year, Roche has been recognised as the most sustainable company in the Pharmaceuticals Industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2017 employed about 94,000 people worldwide. In 2017, Roche invested CHF 10.4 billion in R&D and posted sales of CHF 53.3 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.

VENTANA and BenchMark are trademarks of Roche. Other product names and trademarks are the property of their respective owners.

For further information
Gabrielle Fimbres
Roche Tissue Diagnostics
Phone: +1 520.222.4573
Email: gabrielle.fimbres@roche.com
diagnostics.roche.com

References
1. This product is intended for in vitro diagnostic (IVD) use
2. Greco A, Mariani C, et al. The DNA rearrangement that generates the TRK-T3 oncogene involves a novel gene on chromosome 3 whose product has potential coiled-coil domain. Mol Cell Bio. 1995;15(11)6118-6127.
3. Brzezianska E, Karbownik M, et al. Molecular analysis of the RET and NTRK1 gene rearrangements in papillary thyroid carcinoma in the Polish population. Mutat Res.2006;599(1-2):26-35.
4. De Braud FG, Pilla L, et al. Phase 1 open label, dose escalation study of RXDX101, an oral pan-trk, ROS1, and ALK inhibitor, in patients with advanced solid tumors with relevant molecular alterations. 2014 ASCO Annual Meeting; Abstract 2502.
5. Fernandez-Cuesta L, Peifer M, et al. Cross-entity mutation analysis of lung neuroendocrine tumors sheds light into their molecular origin and identifies new therapeutic targets. 105th Annual Meeting of the American Association for Cancer Research, 2014, San Diego, California, AACR.
6. Leeman-Neill RJ, Kelly LM, et al. ETV6-NTRK3 is a common chromosomal rearrangement in radiation-associated thyroid cancer. Cancer. 2014;120(6):799-807.
7. Ross JS, Wang K, et al. New routes to targeted therapy of intrahepatic cholangiocarcinomas revealed by next-generation sequencing. Oncologist. 2014;19(3):235-242.
8. Vaishnavi A, Capelletti M, et al. Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Nature Medicine. 2013;19(11):1469-1472.
9. Argani P, Fritsch M, et al. Detection of the ETV6-NTRK3 chimeric RNA of infantile fibrosarcoma/cellular congenital mesoblastic nephroma in paraffin-embedded tissue: application to challenging pediatric renal stromal tumors. Mod Pathol. 2000;13(1):29-36.
10. Bishop JA, Yonescu R, et al. Utility of mammaglobin immunohistochemistry as a proxy marker for the ETV6-NTRK3 translocation in the diagnosis of salivary mammary analogue secretory carcinoma. Hum Pathol. 2013;44(10):1982-1988.
11. Bourgeois JM, Knezevich SR, et al. Molecular detection of the ETV6-NTRK3 gene fusion differentiates congenital fibrosarcoma from other childhood spindle cell tumors. Am J Surg Pathol. 2000;24(7):937-946.
12. Rubin BP, Chen CJ, et al. Congenital mesoblastic nephroma t(12;15) is associated with ETV6-NTRK3 gene fusion: cytogenetic and molecular relationship to congenital (infantile) fibrosarcoma. Am J Pathol. 1998;153(5):1451-1458.
13. Tognon C, Knezevich SR, et al. Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma. Cancer Cell. 2002;2(5):367-376.
14. Passinen-Sohns A, Koelzer VH, et al. Single-Center Experience with a Targeted Next Generation Sequencing Assay for Assessment of Relevant Somatic Alterations in Solid Tumors. Neoplasia. 2017;19(3):196-206.
15. Oncomine^TM Focus Assay, Part I: Library Preparation USER GUIDE. Document number: MAN0015819.B.0.
16. Oncomine^TM Focus Assay Part II: Plan a Run, Template Preparation, and Sequencing USER GUIDE. Document number. MAN0015820.A.0.
17. Velizheva NP, Rechsteiner MP, et al. Targeted next-generation-sequencing for reliable detection of targetable rearrangements in lung adenocarcinoma—a single center retrospective study. Path research and prac. 2018;214:572-578.