AML Trial Halted Due to COVID-19 Pandemic
March 30, 2020 09:08pm
By Lisa Astor
Venetoclax in combination with azacytidine demonstrated a statistically significant improvement in overall survival and achieved a satisfactory composite complete remission rate in previously untreated patients with acute myeloid leukemia, meeting the co-primary end points of the phase III VIALE-A study. Genentech, the developer of venetoclax, announced the positive news in a press release, also noting that safety profiles of both drugs were consistent with prior reports.
Venetoclax (Venclexta) in combination with azacytidine demonstrated a statistically significant improvement in overall survival (OS) and achieved a satisfactory composite complete remission rate in previously untreated patients with acute myeloid leukemia (AML), meeting the co-primary end points of the phase III VIALE-A study (NCT02993523). Genentech, the developer of venetoclax, announced the positive news in a press release, also noting that safety profiles of both drugs were consistent with prior reports.1
“Acute myeloid leukemia remains a challenging blood cancer, with particularly low median survival rates in patients who cannot tolerate intensive chemotherapy given their age or underlying health,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, Roche, in a statement. “These data validate the benefit that this Venclexta-based combination can bring to patients and we look forward to discussing the results with health authorities.”
The data will be submitted to global health authorities and presented at an upcoming medical meeting.
If these data are anything like prior data around venetoclax combinations in AML, it will likely show both efficacy and tolerability in the patient population.
In a phase Ib study presented at an American Society of Hematology (ASH) Annual Meeting and subsequently published inBlood, venetoclax plus either azacytidine or decitabine demonstrated a favorable overall response rate (ORR) of 68%, which included complete responses (CRs), complete responses with incomplete count recovery (CRi), and partial responses (PRs). The study also showed an overall leukemia response rate (ORR + morphologic leukemia-free state) of 83%, with most patients tolerating treatment with either combination.2
The most common adverse events (AEs) of any grade observed with the venetoclax combinations in the phase Ib study were febrile neutropenia, nausea, constipation, diarrhea, fatigue, decreased appetite, and decreased white blood cell count.
The randomized, double-blind, placebo-controlled VIALE-A study also looked into the ORR (CR + CRi) with venetoclax and azacytidine as a co-primary end point, as well as OS. The secondary end points of the study were event-free survival, global health status/quality of life (QoL), the percentage of patients achieving a composite CR, CR or CR with partial hematologic recovery rate, the post-baseline transfusion independence rate, CR rate, and fatigue/QoL.1
In the study, patients in the active comparator arm received venetoclax 400 mg orally daily (QD) on days 1 through 28 plus subcutaneous or intravenous azacytidine 75 mg/m2QD on days 1 through 7 of a 28-day cycle. Patients in the placebo arm received a matching dose of venetoclax with a placebo dosage equivalent to azacytidine.
A total of 431 patients were enrolled who were aged 18 years or older and ineligible for induction therapy. Patients were required to have an ECOG performance status of 0 to 2 if they were aged 75 years or older and an ECOG performance status of 0 to 3 if they were aged 18 to 74 years of age. Adequate renal and liver function were also required in all participants.
Individuals were ineligible for the VIALE-A study if they had prior treatment with a hypomethylating agent, venetoclax, or another chemotherapeutic agent for myelodysplastic syndrome (MDS), chimeric antigen receptor T-cell therapy, experimental therapies for MDS or AML. Other factors that may have excluded patients from the study included current participation in another research or observational study, active infection, known central nervous system involvement, history of myeloproliferative neoplasms, acute promyelocytic leukemia, and history of prior malignancies within 2 years of beginning treatment in the study.
Venetoclax is a first-in-class drug that selectively binds and inhibits the B-cell lymphoma-2 protein. Development of the drug is a joint effort between Roche and AbbVie.
Venetoclax has been granted FDA Breakthrough Therapy Designations for indications in previously untreated chronic lymphocytic leukemia (CLL), 2 for relapsed or refractory CLL, and 2 for previously untreated AML. In addition to the treatment of patients with AML and CLL, the drug is also indicated for the treatment of patients with small lymphocytic lymphoma.