^
Association details:
| Biomarker: | IDH1 mutation |
|---|---|
| Cancer: | Acute Myelogenous Leukemia |
| Drug: | Venclexta (venetoclax) (Bcl2 inhibitor) + Tibsovo (ivosidenib) (IDH1 inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
AMLM26/T2 INTERCEPT: A multi-arm trial for patients with acute myeloid leukaemia investigating new treatments which target early relapse and changes in disease characteristics - Ivosidenib + Venetoclax
Excerpt:
...Presence of an IDH1 mutation in a bone marrow or peripheral blood sample taken no more than 28 days prior to cycle 1 day 1 of treatment on this treatment arm...
Trial ID:
Source:
Title:
A phase Ib/II study of ivosidenib with venetoclax +/- azacitidine in IDH1-mutated myeloid malignancies
Published date:
04/27/2023
Excerpt:
The safety and efficacy of combining the IDH1 inhibitor ivosidenib (IVO) with the BCL2 inhibitor venetoclax (VEN; IVO+VEN) +/- azacitidine (AZA; IVO+VEN+AZA) was evaluated in four cohorts of patients with IDH1-mutated myeloid malignancies…Composite complete remission with IVO+VEN+AZA vs. IVO+VEN was 90% vs. 83%....No IDH isoform switching or second-site IDH1 mutations were observed, indicating combination therapy may overcome established resistance pathways to single-agent IVO.
Secondary therapy:
azacitidine
DOI:
10.1158/2643-3230.BCD-22-0205
Source:
Title:
2746 Phase Ib/2 Study of Oral Decitabine/Cedazuridine (ASTX727) and Venetoclax in Combination with the Targeted Mutant IDH1 Inhibitor Ivosidenib or the Targeted Mutant IDH2 Inhibitor Enasidenib in IDH Mutated Acute Myeloid Leukemia
Published date:
11/03/2022
Excerpt:
Patients received a median of 4 treatment cycles (ND: 5, R/R: 3). The CRc rate in the overall population was 72% (ND: 100%, R/R: 53%). Measurable residual disease (MRD) negative CRc by flow cytometry was achieved in 64% (ND: 83%, R/R: 42%)...The combination of ASTX727 + VEN with IDH1 or IDH2 inhibition appears to be an effective regimen for the treatment of IDH mutated AML with high response rates including MRD-negative CRc, most notably in de novo patients and R/R pts without prior VEN exposure.
Secondary therapy:
decitabine/cedazuridine
DOI:
https://doi.org/10.1182/blood-2022-164986
Source:
Title:
A phase Ib/II study of ivosidenib with venetoclax +/- azacitidine in IDH1-mutated myeloid malignancies.
Published date:
05/19/2021
Excerpt:
Eligible patients age ≥18 with IDH1+ MDS, newly diagnosed AML (ND: treatment naïve [TN] or secondary/treated secondary AML [sAML]), or relapsed/refractory (R/R) AML enrolled into three dose levels (DL): DL1 (IVO+VEN 400 mg), DL2 (IVO+VEN 800 mg), DL3 (IVO+VEN 400 mg+AZA)...The ORR was 92% (DL1: 67%, DL2: 100%, DL3: 100%)...IVO+VEN +/- AZA is an effective treatment regimen in patients with IDH1+myeloid malignancies.
Secondary therapy:
azacitidine
DOI:
10.1200/JCO.2021.39.15_suppl.7012
Trial ID:
Source:
Title:
A phase Ib/II study of ivosidenib with venetoclax +/- azacitidine in IDH1-mutated myeloid malignancies.
Published date:
05/19/2021
Excerpt:
Eligible patients age ≥18 with IDH1+ MDS, newly diagnosed AML (ND: treatment naïve [TN] or secondary/treated secondary AML [sAML]), or relapsed/refractory (R/R) AML enrolled into three dose levels (DL): DL1 (IVO+VEN 400 mg), DL2 (IVO+VEN 800 mg), DL3 (IVO+VEN 400 mg+AZA)...The ORR was 92% (DL1: 67%, DL2: 100%, DL3: 100%)...IVO+VEN +/- AZA is an effective treatment regimen in patients with IDH1+myeloid malignancies.
DOI:
10.1200/JCO.2021.39.15_suppl.7012
Trial ID:
Source:
Title:
A PHASE IB/II STUDY OF IVOSIDENIB WITH VENETOCLAX +/- AZACITIDINE IN IDH1-MUTATED MYELOID MALIGNANCIES
Published date:
05/12/2021
Excerpt:
Eligible patients age ≥18 with IDH1+ MDS, newly diagnosed (ND: treatment naïve [TN], secondary/treated secondary AML [sAML]), or relapsed/refractory (R/R) AML were enrolled into three dose levels (DL): DL1 (IVO+VEN 400 mg), DL2 (IVO+VEN 800 mg), DL3 (IVO+VEN 400 mg+AZA)… IVO+VEN +/- AZA is an effective treatment regimen in patients with IDH1+ myeloid malignancies.
Secondary therapy:
azacitidine
Source:
Title:
A PHASE IB/II STUDY OF IVOSIDENIB WITH VENETOCLAX +/- AZACITIDINE IN IDH1-MUTATED MYELOID MALIGNANCIES
Published date:
05/12/2021
Excerpt:
Eligible patients age ≥18 with IDH1+ MDS, newly diagnosed (ND: treatment naïve [TN], secondary/treated secondary AML [sAML]), or relapsed/refractory (R/R) AML were enrolled into three dose levels (DL): DL1 (IVO+VEN 400 mg), DL2 (IVO+VEN 800 mg), DL3 (IVO+VEN 400 mg+AZA)… IVO+VEN +/- AZA is an effective treatment regimen in patients with IDH1+ myeloid malignancies.
Source:
Title:
1339 - Investigations into rational combination approaches with ivosidenib in a mutant IDH1 acute myeloid leukemia patient-derived xenograft model
Published date:
03/10/2021
Excerpt:
...studies were undertaken to explore the IVO + AZA combination in a mIDH1 AML patient-derived xenograft (PDX) model in vivo....The IVO + AZA combination led to a > 99% reduction in hCD45+ cells within the bone marrow and undetectable disease in the peripheral blood of 7/10 mice by Week 10....Similar results were observed with IVO + VEN treated animal bone marrow (99% reduction in hCD45+ cells) and undetectable disease was observed in 8/10 mice by week 10.
Secondary therapy:
azacitidine
