Plasmacytoid variant of urothelial carcinoma
Plasmacytoid carcinoma of the urinary bladder or plasmacytoid urothelial carcinoma (PUC) is rare and only recently described a histological variant of transitional cell carcinoma. The morphological resemblance of PUC to other malignancies is a source of diagnostic dilemmas and often misdiagnosis. Immunohistochemistry plays a pivotal role in narrowing the differential diagnosis and reaching to a conclusive diagnosis. A diagnosis of PUC usually carries a dismal prognosis.

Development-stage biopharma company Loxo Oncology has begun a collaboration with Ventana Medical Systems to develop and commercialize a pan-TRK immunohistochemistry (IHC) test as a companion diagnostic to identify patients across tumor types suitable for treatment with larotrectinib.

Loxo Oncology and Ventana, a member of the Roche Group of companies, will focus their work on an investigational assay developed by Loxo with the intention of further developing the technology on Roche’s OptiView DAB detection technology. First steps will be to optimize and validate the assay to ensure that it performs at a level that could stand up to clinical and regulatory approval.

“We are excited to partner with Roche, the global leader in developing and commercializing IHC assays for cancer diagnostics,” said Josh Bilenker, M.D., CEO of Loxo Oncology. “Our initial technology assessment suggests that an IHC pan-TRK assay is feasible, which is exciting since Roche has thousands of Ventana BenchMark instruments installed worldwide. Diagnostics are a crucial part of our commercial strategy, and we believe IHC will be an important tool, alongside next-generation sequencing, that pathologists can employ in screening for patients who may benefit from larotrectinib.”

Larotectinib (LOXO-101) is Loxo’s lead candidate, an oral IND targeting patients with cancers that that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). According to the company, there is a growing body of research indicating that NTRK genes, which encode for TRKs can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. The drug is currently in numerous clinical trials for both adult and pediatric indications including Phase II studies as part of the NCI-MATCH trial and the NAVIGATE global Phase II multicenter basket trial in patients with solid tumors that harbor TRK gene fusions, and the SCOUT Phase I/II trial in pediatric patients, including patients with advanced cancer, TRK gene fusions, and infantile fibrosarcoma.

For the pan-TRK CDx development, Loxo and Ventana plan to first commercialize it globally as an analytical assay, followed by development as a Class III assay for premarket approval by the FDA. Approval from the FDA will be based on the analyses of patient samples from its ongoing LOXO-101 clinical trials to support the clinical claims of the drug. Roche will be responsible for obtaining and maintaining the regulatory approval of the CDx in the U.S., selected countries in the EU, and other countries that accept the CE in vitro diagnostic registration process.

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