A Study Evaluating Venetoclax Alone and in Combination With Azacitidine in Participants With Relapsed/Refractory Myelodysplastic Syndromes (MDS)

A Phase 1b Study Evaluating the Safety and Pharmacokinetics of Venetoclax as a Single-Agent and in Combination With Azacitidine in Subjects With Relapsed/Refractory Myelodysplastic Syndromes

This is a Phase 1b, open-label, multicenter study designed to evaluate the safety and pharmacokinetics of venetoclax as a single-agent and in combination with azacitidine in participants with relapsed/refractory Myelodysplastic Syndromes (MDS).

Inclusion Criteria:

• Subjects who have relapsed or refractory MDS.

• Subject enrolled in venetoclax monotherapy must have documented failure of prior therapy with a hypomethylating agent (HMA). HMA-failure is defined as:

  1. Relapse after initial complete or partial response or hematological improvement after at least 4 cycles of azacitidine or at least 4 cycles of decitabine within the last 5 years, OR
  2. Failure to achieve complete or partial response or hematological improvement after at least 4 cycles of azacitidine or at least 4 cycles of decitabine within the last 5 years

• Subjects must have presence of < 20% bone marrow blasts per bone marrow biopsy/aspirate at screening.

• Subject is not a candidate to undergo allogenic hematopoietic stem cell transplantation (HSCT).

• Subject must have an Eastern Cooperative Oncology Group (ECOG) performance score of ≤2.

• Subject must have adequate hematologic, renal, and hepatic function.

Exclusion Criteria:

• Subject has received prior therapy with a BH3 mimetic.
• Subject has MDS evolving from a pre-existing myeloproliferative neoplasm (MPN).
• Subject has MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (CML), juvenile myelomonocytic leukemia (JMML) and unclassifiable MDS/MPN.
• Subject has received allogeneic HSCT or solid organ transplantation.
• Subject has received a live attenuated vaccine within 4 weeks prior to the first dose of study drug.
• Subject is pregnant or breastfeeding.