Study design
toxicities, DLTs, failure of prior therapy with an HMA
ONCOLOGY, REMISSION
This open‐label, multicenter study in patients with R/R MDS consisted of three cohorts: Cohort‐1 evaluated venetoclax monotherapy at 400 mg once daily (QD) and 800 mg QD; Cohort‐2 included escalating doses of venetoclax (100, 200, and 400 mg) in combination with azacitidine, evaluated the dose‐limiting toxicities (DLTs), and determined the maximal tolerated dose (MTD); Cohort‐3 evaluated the safety and efficacy of venetoclax (400 mg QD) with azacitidine (Figure Patients ≥18 years of age with R/R MDS were enrolled. Patients enrolled in venetoclax monotherapy had documented failure of prior therapy with an HMA (HMA failure defined as relapse after initial complete remission [CR] or partial remission [PR] or hematologic improvement [HI] or failure to achieve any of these responses after at least four cycles of either azacitidine or decitabine within the last 5 years). Eligible patients had <20% bone marrow (BM) blasts per BM biopsy/aspirate at screening, not current candidates for allogeneic hematopoietic stem cell transplantation and had an Eastern Cooperative Oncology Group (ECOG) performance score of ≤2. Patients were excluded if they had myelodysplastic/myeloproliferative neoplasms or therapy‐related MDS, prior therapy with a BH3 mimetic, or had undergone prior transplantation. The local ethics committee approval was obtained, and the patients gave written informed consent. The study was conducted in accordance with the International Conference on Harmonization, Good Clinical Practice Guidelines, and the Declaration of Helsinki.Venetoclax was administered orally, once daily, with food. Patients on venetoclax monotherapy received 400 or 800 mg once daily for a 28‐day cycle. Escalating doses of venetoclax were evaluated in combination with azacitidine for DLTs. Patients on the combination received venetoclax (100, 200, or 400 mg) during Days 1–14 of the 28‐day cycle. Azacitidine was administered at a standard dose of 75 mg/m