Insight Genetics, Inc. | Date: 2017-02-22
Disclosed are methods and compositions for detecting the presence of an anaplastic lymphoma kinase (ALK) related cancer in a subject and assessing the efficacy of treatments for the same. The disclosed method use reverse transcription polymerase chain reaction (RT-PCR) and multiplex polymerase chain reaction techniques as well as Template Exchange Extension Reaction (TEER) to detect the presence of point mutations, truncations, or fusions of anaplastic lymphoma kinase (ALK).
Insight Genetics, Inc. | Date: 2013-09-26
Disclosed are methods, assays, and compositions for detecting the presence of a kinase inhibitor resistance. The disclosed method and primer panels work with any method for detecting nucleic acid variation in a sample including, but not limited to next generation sequencing.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.50M | Year: 2012
Constitutively activated forms of ALK caused by genetic aberrations have been shown to cause an expanding variety of human cancers. The FDA recently approved the Pfizer drug Xalkori (crizotinib) to treat patients with non-small cell lung cancers (NSCLC) that express ALK. Numerous other pharmaceutical companies (ARIAD, Novartis, Synta, Xcovery, others) have ongoing ALK small-molecule inhibitor programs. The current diagnostic standard an ALK break-apart FISH assay has low sensitivity and is difficult tointerpret, creating a precarious situation for clinicians attempting to select the proper patients for ALK inhibitor treatment. Insight Genetics has therefore designed a qPCR platform, Insight ALK Screen , to provide highly sensitive and unambiguous identification of the complete spectrum of oncogenic ALK. During Phase I development, Insight ALK Screen was shown to be agnostic with regard to the 5 fusion partner of ALK, highly sensitive in cell line dilution studies, and highly specific in FFPE NSCLC patient specimens. Phase II will demonstrate clinical utility of the assay by testing a large cohort of clinical specimens to unequivocally demonstrate statistical significance in sound patient selection for ALK inhibitor therapy. The product will then enter co-development with IVD partner, QIAGEN, for commercialization of the assay as a FDA-approved companion diagnostic.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 199.58K | Year: 2012
Lung cancer is the main cause of cancer mortality worldwide with 80% non-small cell lung cancer (NSCLC) in type and mainly driven by three mutually exclusive oncogenes, EGFR, KRAS and ALK (collectively between 30-60% of all NSCLC cases). Oncogenic driverssuch as ROS1 and RET fusions and DEPDC1 over-expression have been identified as clearly recurrent, collectively constituting up to ~12% of all NSCLC cases. Preclinical studies have demonstrated ROS1-driven cancers to be exquisitely sensitive to small-molecule tyrosine kinase inhibitors (TKIs) as well as Hsp90 inhibitors that are now under development by several pharma and biotech firms. Similarly, ambiguous TKI treatments have also been used against non-NSCLC RET and DEPDC1 driven cancers in ongoing Phase Iand Phase II clinical trials with good efficacy. These trials should encourage numerous pharmaceutical companies to follow suit and conduct similar clinical trials using therapeutics specifically targeting RET and DEPDC1-driven NSCLC. Unfortunately, no regulatory-approved, high-throughput commercial diagnostic tests are readily available to reliably and efficiently diagnose ROS1 or RET fusions nor DEPDC1 over expression in NSCLC patients. We propose to complete the development and validation of both a comprehensive panel of quantitative polymerase chain reaction (qPCR)-based assays and a fluorescence in situ hybridization (FISH) assay to collectively be used as a broad-based NSCLC detection panel to classify a previously unidentified, yet significant, cohort of NSCLC patients readily treatable with available therapeutics. All validations will establish clinical utility by ultimately testing a large cohort of clinical specimens to unequivocally demonstrate statistical significance for sound patient selectionof inhibitor therapy. All potential companion diagnostics will then enter co-development with an IVD partner for full commercialization of each assay as a FDA-approved companion diagnostic.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.50M | Year: 2013
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 193.64K | Year: 2011
Kinase inhibitors have revolutionized cancer treatment but their use has led to drug resistance, prompting development of follow-on inhibitors for resistant tumors. Anaplastic lymphoma kinase (ALK) was discovered by Dr. Stephan Morris (Insight Genetics collaborator on these studies). ALK fusion genes and activating point mutations cause several cancers, and multiple pharmaceutical firms are developing ALK inhibitors. One inhibitor PF-02341066 (crizotinib, Pfizer) has entered Phase III trials and will likely receive FDA approval in 2011. The Morris group has identified a large number of ALK kinase domain mutations that confer high-level PF-02341066 resistance, which has already been reported in patients. A clinical genetic test to identify inhibitor-resistance mutations is needed to guide the development and use of next-generation ALK inhibitors for patients resistant to 1st-generation therapy. The work proposed herein will develop a clinical diagnostic assay for ALK inhibitor-resistance mutations to address this unmet need. Objective 1. Development and application of a genetic diagnostic assay to detect all known ALK inhibitor-resistance mutations using an allele-specific PCR platform. Objective 2: Demonstration and validation of the ability of the test to identify ALK mutations from both cell lines with ALK inhibitor resistance and re-biopsied lung cancer specimens from patients who developed PF-02341066 resistance.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 200.00K | Year: 2010
Kinase inhibitors such as Gleevec and Tarceva have markedly improved cancer therapy. Essential to the use of such inhibitors are companion diagnostics enabling determination of the mutational status of th eir kinase targets in tumors. Anaplastic lymphoma kinase (ALK) fusion oncogenes have emerged as an important cause of lung cancer, and ALK inhibitor programs (by Pfizer, Lil ly, Ariad, Astell as, Zenobia, and others) are in progress, ALK inhibition causes marked anti-tumor responses, but only in patients whose tumors conta in mutant ALK. Both immunohistochemistry (IHe) and fluorescence in situ hybridization (FISH) can identify ALK mutations, but each has multiple limitations Herein, we propose development of a microarray¿based test to ident ify ALK fus ions (EML4¿ALK. NPM¿ALK, CL TC-ALK, and others) from FFPE tissues as a rapid, highly specific and sensit ive companion diagnostic. Insight Genetics has established collaborations with experts in the genetics of ALK and lung cancer, as well as collaborations with pharmaceutical companies developing ALK inhibitors. In the studies proposed, we wi ll establish and validate our ALK mutation detection platform using lung cancer specimens. many also characte rized by ALK FISH and/or IHC to benchmark our assay against these methodolog ies. The Insight Genetics ALK microarray will enable personalized therapy by caregive rs, tra ns lating to improved patient outcomes.
Insight Genetics, Inc. | Date: 2013-03-08
Disclosed are methods and compositions for detecting the presence of a cancer in a subject and assessing the efficacy of treatments for the same. The disclosed method use reverse transcription polymerase chain reaction (RT-PCR), real time polymerase chain reaction, and multiplex polymerase chain reaction techniques to detect fusions, over-expression, truncation, and nucleic acid variation of RET and DEPDC1 in cancers.
Insight Genetics, Inc. | Date: 2014-06-13
Disclosed are methods and kits for detecting the presence of a cancer in a subject and assessing the efficacy of treatments for the same. The disclosed method use reverse transcription polymerase chain reaction (RT-PCR) techniques to detect the presence of point mutations, truncations, or fusions of anaplastic lymphoma kinase.