Guardant Health, the market leader in liquid biopsies, and Mirati Therapeutics, Inc. (Mirati), a targeted oncology company focusing on genetic and epigenetic drivers of cancer, have entered into a collaboration for the development of a circulating tumour DNA (ctDNA) assay for Mirati's kinase inhibitor, glesatinib.

Guardant360 is a blood test that identifies multiple tumour mutations across all four types of genomic alterations: single nucleotide variations, copy number amplifications, indels, and fusions. As part of the collaboration with Mirati, Guardant360 will be used to screen NSCLC patients for certain genetic alterations to the MET pathway in order to identify the patients most likely to respond to glesatinib. Specifically, the assay will sequence for patients with certain MET mutations and MET gene amplification. This plasma-based assay offers a less invasive, and potentially safer, approach to assess tumour genetics by avoiding the risks associated with tumour biopsies. This is an important factor for lung cancer patients for whom repeated tumour biopsies are often not possible. The ability to perform multiple ctDNA blood assays will also facilitate the identification of key resistance mechanisms.

The collaboration will use Guardant360 in Mirati's phase 2 clinical trial of glesatinib in patients with NSCLC. In a separate press release, Mirati announced the initiation of the phase 2 trial. If successful, the collaboration could result in a regulatory submission and approval of the Guardant360 platform as a companion diagnostic for glesatinib.

"Guardant360 is particularly useful for cancers driven by evolved mutations like MET amplifications. The non-invasive assay allows oncologists to quickly and easily monitor patients and their response to targeted therapies," said Guardant Health co-founder and CEO, Helmy Eltoukhy. "Mirati is a pioneer in the field of targeted therapeutics and the company is known for being an innovator. Today's collaboration will allow us to leverage our unique technology to provide more patients access to targeted trials, and potentially accelerate clinical studies, making cancer a more manageable disease."

"Identifying patients with MET mutations or MET gene amplification is the key to our patient selection strategy. Clinical data has shown that these are the patients most likely to respond to glesatinib," said Charles M. Baum, M.D., Ph.D., president and CEO, Mirati.

"Collaborating with Guardant on a ctDNA assay means that we expect to be able to detect these mutations in a blood sample. This will enable the more than 30 per cent of non-small cell lung cancer patients, who have insufficient tumour tissue for biopsy, to be screened for genetic alterations that may be driving their cancer and to seek treatment that could lead to improved outcomes."

Glesatinib (MGCD265) is a tyrosine kinase inhibitor that is expected to potently and selectively target tumors in patients with driver alterations in MET (mutations and gene amplification) and Axl (rearrangements) that occur in approximately 8 per cent of patients with non-small cell lung cancer (NSCLC). Glesatinib is being evaluated in a phase 1b study in patients with solid tumours that have genetic alterations in MET or AXL genes. The phase 2 trial in NSCLC patients with MET genetic alterations is underway to confirm and extend the data that supports the clinical benefit of glesatinib in patients with driver mutations in MET. Genetic alterations in these targets have been implicated as drivers of tumor growth and disease progression in NSCLC, gastroesophageal cancer and other solid tumours. MET and Axl are also implicated as drivers of tumor progression in patients whose tumors have become resistant to EGFR inhibitors. Therefore, Mirati believes that the combination of glesatinib with an EGFR inhibitor could potentially treat patients who have become resistant to agents targeting EGFR. Mirati retains worldwide rights to glesatinib.

Guardant360 is the first CLIA/CAP-certified comprehensive next generation sequencing-based liquid biopsy test indicated for cancer genomics. The 70-gene blood test is used in advanced cancer patients with visceral solid tumor cancers or metastases, and interrogates all four types of genomic alterations. The test is used to prevent repeat invasive biopsies when cancer has progressed or recurred despite treatment, or when an initial biopsy is unobtainable or has insufficient tissue. It is the only ctDNA test that includes all NCCN somatic genomic targets in a single test. Unlike hotspot tests, Guardant360 sequences complete exons so as not to miss uncommon or rare mutations. Based on the tumor genomic profile, clinicians receive a report of actionable genomic alterations and a list of FDA -approved treatments and clinical trials for which the patient could be eligible. Guardant360 has undergone extensive analytical and clinical validation and is supported by publications with leading cancer centers globally.