Molecular Profile Detail

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Profile Name BTK T474I BTK C481S
Gene Variant Detail

BTK C481S (no effect)

BTK T474I (no effect)

Relevant Treatment Approaches

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
BTK T474I BTK C481S Advanced Solid Tumor predicted - resistant Ibrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Imbruvica (ibrutinib) failed to inhibit Btk activity in a cell line expressing BTK variants T474I and C481S in culture (PMID: 33526860). 33526860
BTK T474I BTK C481S Advanced Solid Tumor predicted - resistant Acalabrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Calquence (acalabrutinib) failed to inhibit Btk activity in a cell line expressing BTK variants T474I and C481S in culture (PMID: 33526860). 33526860
BTK T474I BTK C481S Advanced Solid Tumor predicted - resistant Zanubrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Brukinsa (zanubrutinib) failed to inhibit Btk activity in a cell line expressing BTK variants T474I and C481S in culture (PMID: 33526860). 33526860
BTK T474I BTK C481S Advanced Solid Tumor predicted - sensitive RN486 Preclinical - Biochemical Actionable In a preclinical study, treatment with RN486 resulted in reduced Btk activity in a cell line expressing BTK variants T474I and C481S in culture (PMID: 33526860). 33526860
BTK T474I BTK C481S Advanced Solid Tumor predicted - sensitive Fenebrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Fenebrutinib (GDC-0853) resulted in reduced Btk activity in a cell line expressing BTK variants T474I and C481S in culture (PMID: 33526860). 33526860
BTK T474I BTK C481S Advanced Solid Tumor predicted - resistant CGI1746 Preclinical - Biochemical Actionable In a preclinical study, treatment with CGI1746 failed to inhibit Btk activity in a cell line expressing BTK variants T474I and C481S in culture (PMID: 33526860). 33526860
BTK T474I BTK C481S chronic lymphocytic leukemia predicted - resistant Tirabrutinib Case Reports/Case Series Actionable In Phase I trials, a patient with chronic lymphocytic leukemia progressed on treatment with Tirabrutinib (ONO-4059) and was subsequently found to have acquired BTK C481S and T474I (PMID: 37257190, NCT01659255 and NCT02457598). 37257190
BTK T474I BTK C481S chronic lymphocytic leukemia predicted - resistant Pirtobrutinib Case Reports/Case Series Actionable In a clinical case study, Jaypirca (pirtobrutinib) treatment resulted in a continued decrease of cancer cell fraction (CCF) of a clone of cells harboring BTK C481S but persistent increase of a clone harboring BTK T474I in a patient with chronic lymphocytic leukemia, as well as low-level CCF increase of BTK T474L, and BTK M477I (PMID: 36287227). 36287227