KEY TAKEAWAYS
- The OMNIVERSE phase I trial aimed to assess the safety, tolerability, and preliminary efficacy of Oral-AZA + VEN and determine the MTD in R/R AML pts.
- The primary endpoints were safety and tolerability to establish MTD of Oral-AZA + VEN.
- The study found that the drug combination was well-tolerated and exhibited a safety profile consistent with the individual agents.
The combination of venetoclax (VEN) and injectable azacitidine is an effective treatment of acute myeloid leukemia(AML) patients(pts) who are not eligible for intensive chemotherapy. Oral-azacitidine (AZA) offers the potential for extended dosing schedules and improved convenience compared to injectable aza.
Researchers aimed to assess the safety, tolerability, and preliminary efficacy of Oral-AZA + VEN and determine the maximum tolerated dose(MTD) in relapsed/refractory(R/R) AML pts.
The study included IC-ineligible adults with R/R AML (ECOG performance status ≤2). The intervention included an initial Oral-AZA dose of 300 mg QD for 14 days per 28-day cycle and VEN at 400 mg QD for 28 days. Dose adjustments based on dose-limiting toxicities (DLTs) may lead to de-escalation to Oral-AZA 200 mg QD for 14 days + VEN 400 mg QD for 28 days or Oral-AZA 200 mg QD for 14 days + VEN 400 mg QD for 21 days.
The primary endpoints were safety and tolerability to establish the MTD of Oral-AZA + VEN. Secondary endpoints included preliminary response rates based on European LeukemiaNet 2017 criteria for complete remission (CR), CR with partial hematologic recovery, CR with incomplete blood count recovery (CRi), and overall response(OR).
About 6 pts (aged 21–80 years; 3 female) underwent 1–14 cycles of Oral-AZA + VEN. Four patients experienced ≥1 any-grade drug-related adverse events, including grade 1–3 diarrhea (n=2) and grade 1–2 nausea (n=2). About 4 pts reported grade 3 febrile neutropenia unrelated to the drug. One patient had Oral-AZA reduced to 200 mg QD×14d from Cycle 4 due to grade 2 diarrhea and nausea.
VEN was reduced to 70 mg QD×28d from Cycle 2 due to co-treatment with a strong CYP3A inhibitor (per protocol, n=4). Three patients died post-treatment discontinuation. No dose-limiting toxicities (DLTs) were observed, establishing the MTD as Oral-AZA 300 mg QD×14d + VEN 400 mg QD×28d. The best responses included CR (n=1), CRi (n=1), and stable disease (n=4). As of May 2023, 2 patients remain on treatment.
The study found that the drug combination was well-tolerated and exhibited a safety profile consistent with the individual agents.
Source: https://clml-soho2023.elsevierdigitaledition.com/292/index.html
Clinical Trial: https://clinicaltrials.gov/study/NCT04887857
Fleming S, Roboz GJ, Fathi AT, Zhang TY, Wei A, Carraway HE, Holes L, Petrlik E, Prebet T, Menezes DL, Bluemmert I, Sun H, Ravandi F. Phase IB OMNIVERSE Trial: Safety and Tolerability of Oral Azacitidine (Oral‑AZA) in Combination With Venetoclax (VEN) for Treatment of Acute Myeloid Leukemia (AML). Presented at: SOHO 2023
