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Association details:
| Biomarker: | SF3B1 mutation |
|---|---|
| Cancer: | Myelodysplastic Syndrome |
| Drug: | emavusertib (CA-4948) (FLT3 inhibitor, IRAK-4 inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
Study of Orally Administered CA-4948(IRAK4i) as a Monotherapy in patients with Acute Myelogenous Leukemia or Myelodysplastic Syndrome and in Combination with Azacitidine or Venetoclax Estudio para evaluar CA-4948 (IRAK4i) administrado por vía oral en pacientes con leucemia mielógena aguda o síndrome mielodisplásico tanto en monoterapia como en combinación con azacitidina o venetoclax
Excerpt:
...High-risk R/R MDS (IPSS-R criteria) that are considered resistant/refractory following at least 2 to 3 cycles naïve of HMA or evidence of early progressionPhase 1b (Combination Therapy) Doublet Arm: CA-4948 + AZAPatients with:• IPSS- R High, hrMDS• Ineligible for intensive chemotherapyDoublet Arm: CA-4948 + VENPatients with:• R/R AML or hrMDS, after first line therapyPhase 2a Dose Expansion (Monotherapy)Patients with:· R/R AML with FLT3 mutations, R/R including a FLT3 inhibitor · R/R AML with spliceosome mutations of SF3B1 or U2AF1· R/R hrMDS with spliceosome mutations of SF3B1 or U2AF1; bone marrow blast count ≥8%: ineligible for intensive chemotherapy· Number of pretreatments: 1 or 25. ...
Trial ID:
Source:
Title:
Dose Escalation/ Expansion Study of CA-4948 as Monotherapy in Patients With AML or MDS
Excerpt:
...- R/R AML with spliceosome mutations of SF3B1 or U2AF1...
Trial ID:
Less C2 evidence
Source:
Title:
Phase 1/2a study of the IRAK4 inhibitor CA-4948 as monotherapy or in combination with azacitidine or venetoclax in patients with relapsed/refractory (R/R) acute myeloid leukemia or lyelodysplastic syndrome.
Published date:
05/26/2022
Excerpt:
This is an open-label, phase 1/2a dose escalation and cohort expansion trial (NCT04278768). In phase 1 Dose Escalation, patients with R/R AML or HR-MDS are treated with CA-4948 monotherapy...Of 43 patients starting before Sept 30th, 2021, 14 had SF3B1, U2AF1 or FLT3 mutations and demonstrated more promising efficacy...CA-4948 is well tolerated and effective in heavily pretreated AML and HR-MDS patients, especially in those with U2AF1/SF3B1/FLT3 mutations.
DOI:
10.1200/JCO.2022.40.16_suppl.7016
Trial ID:
Source:
Title:
TAKEAIM LEUKEMIA- A PHASE 1/2A STUDY OF THE IRAK4 INHIBITOR EMAVUSERTIB (CA-4948) AS MONOTHERAPY OR IN COMBINATION WITH AZACITIDINE OR VENETOCLAX IN RELAPSED/REFRACTORY AML OR MDS
Published date:
05/12/2022
Excerpt:
In the 7 spliceosome-mutated HR-MDS patients, 57% reached marrow CR, including 1 with RBC transfusion independence and 1 proceeding to HSCT. One of the three FLT3-mutated AML reached CR, and 2 became FLT3-negative. Among the 29 patients without SF3B1/U2AF1/FLT3 mutations, 1 reached CR and 2 PR. Phase 1b and Phase 2a are ongoing. RNA-seq on selected samples showed decrease in relative expression of IRAK4-long isoforms with response to emavusertib. Emavusertib is well tolerated and effective in heavily pretreated AML and HR-MDS patients, especially in those with U2AF1/SF3B1/FLT3 mutations.
Source:
Title:
Curis Announces Updated Data with Additional Encouraging Clinical Activity in Phase 1/2 Study of CA-4948 Monotherapy in Targeted Patients with Relapsed or Refractory AML and MDS; and Initial Clinical Data from Phase 1 Study of CI-8993 in Patients with Relapsed or Refractory Solid Tumors
Published date:
01/06/2022
Excerpt:
...57% ORR (objective response rate) observed in R/R MDS patients with U2AF1 or SF3B1 spliceosome mutation treated with CA-4948...Consistent tumor burden reduction observed, with 4 out of 7 patients achieving ≥ 50% reduction in blast counts
