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| Profile Name | BTK T474I BTK C481S |
| Gene Variant Detail | |
| Relevant Treatment Approaches |
| 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 |