MD Anderson Reports Early Response in Phase 2 Trial of CPX-351 and Ivosidenib Combination
Clinical Design and Treatment Strategy
NCT04493164 is an ongoing single-center Phase 2 trial led by MD Anderson Cancer Center in collaboration with Jazz Pharmaceuticals (JAZZ). It combines Vyxeos (CPX-351; liposomal daunorubicin and cytarabine) with Tibsovo (ivosidenib; mutant IDH1 inhibitor) for patients with IDH1-mutant acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). CPX-351 eliminates leukemia cells, while ivosidenib blocks the production of the oncometabolite 2-hydroxyglutarate to restore myeloid cell differentiation. Although the mechanisms of these two approved drugs are combined, the combination therapy itself is still in development.
Interim Efficacy Signals
As of July 10, 2024, 11 evaluable patients were enrolled, including 4 newly diagnosed and 7 relapsed/refractory cases. The objective response rate (ORR) in newly diagnosed patients was 100%, with 1 complete remission (CR), 2 complete remission with incomplete blood count recovery (CRi), and 1 morphologic leukemia-free state, all of whom were MRD-negative by flow cytometry. The ORR in relapsed/refractory patients was 43%, with 1 CR and 2 CRi, and all 3 responders were MRD-negative. However, this is a single-arm interim analysis with only 11 patients and does not replace confirmatory trial data.
Survival and Safety
The median duration of response in newly diagnosed patients was 16.3 months, with median event-free survival of 17.5 months and median overall survival of 29.3 months. In relapsed/refractory patients, event-free survival was 4.2 months and overall survival was 12.0 months, with 4 responders proceeding to hematopoietic stem cell transplantation. The main treatment-related adverse events were rash (45%), thrombocytopenia (18%), QTc prolongation (9%), and bradycardia (9%). There were no treatment-related deaths or differentiation syndrome. Two grade 4 platelet count reductions were observed in patients with marrow remission, highlighting the key safety concern of delayed hematologic recovery.
Competitive, Regulatory, and Market Context
Competitive benchmarks include 7+3 intensive chemotherapy, CPX-351 monotherapy, and non-intensive regimens such as azacitidine with venetoclax or azacitidine with ivosidenib for eligible patients. For relapsed IDH1-mutant AML, Rezlidhia (olutasidenib; mutant IDH1 inhibitor) is also available. Vyxeos was approved by the FDA on August 3, 2017, and Tibsovo for IDH1-mutant relapsed/refractory AML on July 20, 2018, with EMA approvals on August 23, 2018, and May 4, 2023, respectively. Tibsovo was approved in Japan on March 27, 2025, and no FDA Advisory Committee (AdComm) vote has been held for this combination. The global AML treatment market in 2025 is estimated at USD 3.91 billion, and if MRD-negative remission and transplant linkage are reproducible in large trials, this combination could offer differentiation in the IDH1-mutant submarket.
From an investment perspective, this trial represents an early signal for Jazz Pharmaceuticals (JAZZ)'s approved asset CPX-351 and Servier's Tibsovo to expand into molecularly targeted combination therapy within the USD 3.91 billion global AML treatment market in 2025. While the 100% ORR and 100% MRD negativity in the newly diagnosed group are strong, the sample size is only 4 patients, and the total analysis includes just 11 patients in a Phase 2 trial. Therefore, further enrollment and validation of response durability take precedence over short-term valuation impacts. For researchers, the biological synergy between IDH1 inhibition and liposomal intensive chemotherapy is key, and for the industry, the design of comparative trials against 7+3, CPX-351 monotherapy, and azacitidine with venetoclax or ivosidenib is critical. Long-term competitive strength will depend on transplant conversion rates, duration of MRD negativity, management of long-term thrombocytopenia, and entry into randomized clinical trials.
Source: ClinicalTrials.gov (api_ct)