STAMFORD, Conn. & SAN DIEGO—In April, Loxo Oncology and Illumina Inc. announced a global strategic partnership to develop and commercialize a multigene panel for broad tumor profiling, resulting in a distributable, next-generation sequencing (NGS) based companion diagnostic (CDx) with a pan-cancer indication. The co-development partnership will seek approval for a version of the Illumina TruSight Tumor 170 as a CDx for Loxo Oncology’s larotrectinib (LOXO-101), which targets NTRK gene fusions, and LOXO-292, which targets RET gene alterations, across tumor types.
“We are very excited to announce this collaboration with Illumina, the world’s leader in NGS technology,” says Jacob Van Naarden, chief business officer of Loxo Oncology. “Loxo Oncology is developing targeted therapies for cancers driven by underlying genetic alterations, so diagnostics are critical to identifying appropriate patients. We have piloted numerous NGS assays, and the Illumina TruSight Tumor 170 assay has consistently demonstrated robust performance with its assessment of both DNA and RNA, including highly sensitive gene fusion detection.
“The broad 170-gene assay content has the potential to deliver meaningful insights from a single tumor specimen, identifying patients with NTRK fusions, RET fusions, RET mutations and many other actionable tumor alterations. Furthermore, we believe that this collaboration will improve patient access to high-quality NGS testing because pathologists will be able to run TruSight Tumor 170 locally and receive reimbursement.”
TruSight Tumor 170 is a comprehensive, state-of-the-art, next-generation sequencing test that interrogates point mutations, fusions, amplifications and splice variants in 170 genes associated with common solid tumors. The CDx version of TruSight Tumor 170 will allow local laboratories to provide referring physicians with comprehensive genomic information, so that patients can be matched to the most appropriate therapeutic options. This version of TruSight Tumor 170 will run on Illumina’s NextSeq 550Dx platform.
“We are leveraging our leadership in next-generation sequencing to deliver in-vitro diagnostic solutions to improve the management of cancer patients in the clinic,” said Dr. Garret Hampton, executive vice president of clinical genomics at Illumina. “To this end, we are partnering with leading biotechnology companies, such as Loxo Oncology, to develop companion diagnostics for best-in-class therapeutics. Distributable diagnostic solutions, such as a CDx version of TruSight Tumor 170, in combination with the NextSeq 550Dx platform, will enable labs to perform precision medicine testing in-house.”
Under the partnership, the companies will collaborate to validate a CDx version of TruSight Tumor 170 for NTRK fusions and RET fusions/mutations as a Class III FDA-approved diagnostic in conjunction with larotrectinib and LOXO-292, respectively.
“This co-development partnership will seek FDA approval for a version of the Illumina TruSight Tumor 170 as a companion diagnostic for Loxo Oncology’s larotrectinib and LOXO-292. Loxo Oncology and Illumina will be utilizing the TruSight Tumor 170 assay in its existing form. Loxo Oncology and Illumina are working together diligently to establish a timeline for FDA CDx approval, but can’t provide any other specifics at this time,” Van Naarden notes.
LOXO-292 is an investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase. Both RET fusion and select RET mutated cancers are primarily dependent on this single activated kinase for their proliferation and survival. This dependency, often referred to as “oncogene addiction,” renders such tumors highly susceptible to small-molecule inhibitors targeting RET. LOXO-292 was designed to inhibit native RET signaling as well as anticipated acquired resistance mechanisms that could otherwise limit the activity of this therapeutic approach. LOXO-292 is currently being studied in a Phase 1 trial.
The companies are also planning to broaden the clinical utility of the full panel by obtaining regulatory approval for the other assay content, to be marketed as a tumor profiling test. Illumina will lead regulatory activities related to the Class III plans for NTRK and RET, the Class II plans for the tumor profiling content and CE marking.
“We are focused on doing the work necessary to submit a version of the Illumina TruSight Tumor 170 as a companion diagnostic for Loxo Oncology’s larotrectinib and LOXO-292 to the FDA, as well as for the rest of the panel to be available as a Class II cancer genomic profiling test. We believe that a test with broad applicability across cancers with many interrogated genetic variants has the best chance of being utilized routinely by physicians,” says Van Naarden.
“This collaboration is important because there isn’t a currently available NGS solution that incorporates highly sensitive detection of TRK fusions and RET fusions/mutations, that has the ability to detect many other actionable targets, that is run locally and that can fall under the CMS national coverage determination. We believe that if labs have the ability to run the test locally and receive reimbursement it will increase patient access to high-quality NGS testing,” he concludes.