Angsana Molecular & Diagnostics said today its RNA-based fusions cancer panel will be used for screening TRK, ROS1 and ALK fusions in Ignyta’s Phase II registration clinical trial for its anti-tumor candidate entrectinib.
Angsana will be a partner molecular test laboratory for Ignyta’s STARTRK-2 trial, working with the drug developer to conduct diagnostic screening at trial sites in Asia.
The open-label, multicenter, global, Phase II basket study is designed to assess entrectinib in patients with TRK, ROS1, or ALK gene rearrangements. Enrolled patients will have solid tumors testing positive for those fusions.
Angsana has developed the Solid Tumour Test, designed to identify clinically actionable mutation hotspots, gene rearrangement, and copy number changes. The test is intended to cover the most commonly used gene targets, including:
- EGFR mutation analysis (Exon 18-21 kinase domain) as a predictive indicator for therapeutic response to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) and colorectal cancer.
- KRAS mutation analysis as a predictive indicator for therapeutic response to EGFR targeted treatment in metastatic colorectal cancer and NSCLC.
- BRAF mutation analysis for thyroid papillary carcinoma, melanoma, colorectal cancer and low grade gliomas.
- C-KIT and PDGFRA mutation analysis as predictive indicators for therapeutic response in Gastrointestinal Stromal Tumor (GIST).
- EML4-ALK rearrangement and response to ALK inhibitors in NSCLC.
The test also includes approximately 2,000 mutational hotspots in four categories:
- Actionable driver mutations guiding FDA-approved drugs, such as EGFR mutations in NSCLC for erlotinib, gefitinib and afatinib
- Driver mutations guiding effective drugs used in clinical trials and/or previously approved for use in other tumor types, such as PIK3CA mutations for PI3K pathway inhibitors in clinical trials
- Known drug resistance mutations in genes or in combination with sensitive mutations of genes in the same pathway to guide therapies (e.g. T790M mutation of EGFR for EGFR inhibitors, ESR1 mutations for anti-estrogen and estrogen deprivation therapies, kinase domain mutations in ALK gene for ALK TKIs).
- Mutations that give insightful diagnostic or prognostic information, such as FOXL2 mutations in granulosa cell tumor of the ovary.
Molecular oncology is one of four medical areas for which Angsana develops molecular diagnostic assays; the other three are allergy and molecular allergology, fetal maternal health, and pharmacogenetics.
Established in 2014, Angsana has multi-laboratory CAP accredited operations in Singapore, where the company is headquartered, and in Hong Kong. The company has offices in Hong Kong and Malaysia.
Entrectinib (RXDX-101) is an oral selective inhibitor for all three TRK receptor tyrosine kinases encoded by the three NTRK genes (1, 2, and 3), as well as the ROS1 and ALK receptor tyrosine kinases. Entrectinib is designed to be a once-daily treatment and is being studied in patients whose tumors have tested positive for rearrangements of those genes.
In Phase I data published online in Cancer Discovery, entrectinib generated responses in NSCLC, colorectal cancer, mammary analog secretory carcinoma, melanoma and renal cell carcinoma as early as four weeks after first treatment. Those responses lasted as long as 2.5 years and are still ongoing, according to Ignyta.
Ignyta also found a 79% response rate in 24 patients with TRK, ROS1, or ALK-driven extracranial solid tumors, with entrectinib responses that were both rapid and durable in patients with advanced solid tumors across multiple histologies and each of the molecular targets of interest, including in multiple patients with metastatic CNS disease.