Clinical Design and Progress

VICTORY-MDS/MPN, a Phase 2 randomized clinical trial led by the National Cancer Institute (NCI), enrolled 132 patients with chronic myelomonocytic leukemia (CMML) with a blast count of 5% or greater, and other myelodysplastic/myeloproliferative neoplasms (MDS/MPN). Patients were assigned to either an INQOVI (decitabine/cedazuridine) monotherapy arm or an INQOVI and VENCLEXTA (venetoclax) combination arm, with the possibility of crossover to the combination arm for non-responders in the monotherapy arm. According to ClinicalTrials.gov, the study is currently active and not recruiting, with enrollment completed and follow-up ongoing. The actual start date was June 27, 2023, and the primary completion date is expected to be August 31, 2026.

Mechanism of Action and Evaluation Parameters

INQOVI is an oral fixed-dose combination of decitabine 35mg, which inhibits DNA methyltransferase (DNMT), and cedazuridine 100mg, which blocks cytidine deaminase (CDA) in the gut and liver. VENCLEXTA is a selective inhibitor of the anti-apoptotic protein BCL-2, inducing mitochondrial apoptosis. The combination therapy aims to combine epigenetic reprogramming with the blockade of survival signals. Both arms administer INQOVI on days 1-5 of a 28-day cycle, with the combination arm adding venetoclax on days 1-14. The primary endpoint is the complete remission (CR) rate. Secondary endpoints include overall response rate, overall survival, progression-free survival, rate of hematopoietic stem cell transplantation, and clearance of malignant clones, as well as transfusion burden, to comprehensively assess clinical depth and durability.

Regulatory Status and Commercial Basis

INQOVI is developed by Astex Pharmaceuticals and marketed by Taiho Oncology in the United States, and was approved by the FDA on July 7, 2020, for intermediate- and high-risk MDS and CMML. VENCLEXTA is a BCL-2 inhibitor co-developed by AbbVie and Roche's Genentech, and received accelerated approval from the FDA on November 21, 2018, for relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), followed by full approval on October 16, 2020, for newly diagnosed acute myeloid leukemia (AML) in combination with a hypomethylating agent in elderly or unfit patients. However, the INQOVI and venetoclax combination is not currently approved for CMML or MDS/MPN indications, making this Phase 2 trial a key comparative study for potential indication expansion.

Market and Competitive Landscape

CMML is a rare blood cancer diagnosed in approximately 1,000 people annually in the United States, but including adjacent MDS, the total number of new patients in the United States is approximately 10,000 to 15,000 per year. The current standard of care for CMML is azacitidine and intravenous or oral decitabine-based hypomethylating agents, with allogeneic hematopoietic stem cell transplantation being the only potentially curative treatment option for eligible patients. Competing development efforts include JAK1/2 inhibitors such as ruxolitinib, the GM-CSF antibody lenzilumab, and the CD123-targeted tagraxofusp in combination with hypomethylating agents. AbbVie's VENCLEXTA achieved global sales of USD 2.792 billion in 2025, and the success of this study could add to this figure by providing additional indication momentum, as well as demonstrating the potential for expanding the oral BCL-2 combination platform across MDS/MPN.

Why It Matters

The Phase 2 randomized trial of 132 patients directly compares the addition of VENCLEXTA to INQOVI monotherapy, assessing complete remission rate, survival, and stem cell transplant conversion rate, providing higher decision-making value than non-randomized early studies. In the short term, the efficacy and safety data, including myelosuppression and infection, expected after primary completion in August 2026, could add to AbbVie's 2025 VENCLEXTA sales of USD 2.792 billion by providing an additional indication. In the medium to long term, positive results will raise the bar for the development of azacitidine/decitabine-based CMML standard treatments and competing pipelines such as ruxolitinib and lenzilumab. For researchers and the industry, this study provides a key dataset to determine whether a fully oral DNMT/CDA/BCL-2 multi-mechanism approach can be extended from rare CMML to the broader MDS/MPN market.