Methods of treating cholangiocarcinoma
Inventors
Ali, Siraj Mahamed • Hawryluk, Matthew J. • He, Jie • Lipson, Doron • Miller, Vincent A. • Ross, Jeffrey S. • Stephens, Philip James
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12274699-B2
Publication Date
2025-04-15
Expiration Date
Abstract
Methods and compositions for treating cholangiocarcinoma.
Core Innovation
The invention relates to treating cholangiocarcinoma by determining the presence or absence of a fibroblast growth factor receptor (FGFR) gene fusion or a neurotrophic tyrosine receptor kinase (NTRK) gene fusion in an FGFR or NTRK nucleic acid molecule or polypeptide in a sample obtained from a subject that has or is at risk of having a cholangiocarcinoma. The detection identifies FGFR2 or NTRK1 gene rearrangements that generate specific fusion molecules, including FGFR2-TACC3, FGFR2-KIAA1598, BICC1-FGFR2, FGFR2-BICC1, PARK2-FGFR2, FGFR2-NOL4, ZDHHC6-FGFR2, and RABGAP1L-NTRK1.
Responsive to the determination, the invention generates a report comprising one or more therapeutic options, including a therapeutic agent that antagonizes or inhibits an FGFR gene or gene product or an NTRK gene or gene product when the FGFR or NTRK gene fusion is present. The report links fusion status in patient samples to treatment selection and to identification of likely or unlikely response.
In related methods, the disclosure stratifies a subject for treatment by classifying the subject as a candidate to receive a treatment comprising an FGFR- or NTRK-antagonizing or -inhibiting therapeutic agent when the fusion is present, or a treatment other than such an agent when the fusion is absent. The disclosure also identifies a subject as likely or unlikely to respond to a treatment depending on whether the FGFR or NTRK gene fusion is present or absent.
Claims Coverage
The independent claims cover three linked functions based on detecting FGFR or NTRK gene fusions in samples from subjects with or at risk of cholangiocarcinoma: report generation, treatment stratification, and response prediction. The claims recite three inventive features that use fusion presence or absence to guide therapeutic options and to classify likely versus unlikely response to FGFR/NTRK-targeted therapy.
Detecting FGFR or NTRK gene fusion in a subject sample
Detecting an FGFR or NTRK gene fusion in an FGFR or NTRK nucleic acid molecule or polypeptide in a sample obtained from a subject that has or is at risk of having a cholangiocarcinoma, thereby determining that the FGFR or NTRK gene fusion is present in the sample.
Generating a report with FGFR or NTRK therapeutic options
Responsive to the determination of the presence of the FGFR or NTRK gene fusion in the sample, generating a report comprising one or more therapeutic options comprising a therapeutic agent that antagonizes or inhibits an FGFR gene or gene product or an NTRK gene or gene product.
Stratifying treatment and response by fusion presence or absence
Detecting presence or absence of a fibroblast growth factor receptor (FGFR) gene fusion or a neurotrophic tyrosine receptor kinase (NTRK) gene fusion in an FGFR or NTRK nucleic acid molecule or polypeptide in a sample obtained from the subject, and classifying the subject as a candidate to receive either a treatment comprising an FGFR- or NTRK-antagonizing or -inhibiting therapeutic agent or a treatment other than such an agent, and identifying the subject as likely or unlikely to respond based on fusion presence or absence.
Across the independent claims, the main claim coverage is fusion-biomarker driven decision support for cholangiocarcinoma, using detection of FGFR and/or NTRK gene fusions in nucleic acid molecules or polypeptides to generate therapeutic options, stratify subjects for targeted versus non-targeted treatment, and identify subjects as likely versus unlikely to respond to FGFR/NTRK-targeted therapy.
Stated Advantages
Provides therapeutic options comprising a therapeutic agent that antagonizes or inhibits the FGFR gene or gene product or the NTRK gene or gene product when the corresponding fusion is present.
Enables stratifying subjects with or at risk of cholangiocarcinoma into candidates for fusion-targeted therapy when an FGFR or NTRK gene fusion is present, and into candidates for other treatment when the fusion is absent.
Identifies subjects as likely to respond versus unlikely to respond to fusion-targeted treatment based on presence versus absence of an FGFR or NTRK gene fusion.
Documented Applications
Determining whether an FGFR gene fusion or an NTRK gene fusion is present in a sample from a subject that has or is at risk of having a cholangiocarcinoma, and generating a report with therapeutic options.
Stratifying a subject that has or is at risk of having a cholangiocarcinoma for treatment selection by classifying candidates based on presence or absence of an FGFR or NTRK gene fusion.
Identifying whether a subject that has or is at risk of having a cholangiocarcinoma is likely or unlikely to respond to a treatment comprising an FGFR- or NTRK-antagonizing/inhibiting therapeutic agent based on presence or absence of the relevant gene fusion.
Interested in licensing this patent?