Phase 1/2 Study Tests Quizartinib/Venetoclax/Decitabine in FLT3-ITD AML

Musa Yilmaz, MD, Department of Leukemia, The University of Texas MD Anderson Cancer Center, discusses the most recent update of the phase 1/2 study (NCT03661307) of quizartinib (Vanflyta), venetoclax (Venclexta), and decitabine in FLT3-internal tandem duplication (ITD) mutated acute myeloid leukemia (AML) and the background behind this research.

The study includes 2 cohorts, including 1 with newly diagnosed patients with AML and 1 with relapsed/refractory patients with AML. Quizartinib was given to patients at varying dose levels. Investigators found the recommended phase 2 dose to be 30 mg of quizartinib as it is well-tolerated and effective.

Updated findings were presented at the 2023 American Society of Hematology Annual Meeting.

Transcription:

0:09 | We presented a phase 1/2 clinical trial of decitabine, venetoclax, and quizartinib. This is not the first presentation, this is the update. Most importantly, we have now treated 14 patients with newly diagnosed FLT3-ITD mutated AML. Out of these 14 patients, all of them, 14, had a response. About 80% of these responses are complete remissions, and the remaining 20% are complete remissions with incomplete count recoveries.

0:43 | The standard-of-care treatment for the older patients who are not fit for intensive chemotherapy is either azacitidine or a hypomethylating agent in combination with venetoclax. We know that outcomes with this combo, in particular in patients with FLT3-ITD mutated AML, is about 10 months, the median overall survival. This is obviously poor and needs to be improved. Some of the preclinical studies have shown that combining a FLT3 inhibitor, such as crizotinib, with BCL2 inhibitor, such as venetoclax, has shown synergism and causes the death of the FLT3-positive cell lines. Also, preclinical models have shown that. Based on this rationale, we developed this phase 1/2 clinical study.

REFERENCE:

Yilmaz M, Muftuoglu M, DiNardo CD, et al. Phase I/II study of quizartinib, venetoclax, and decitabine triple combination in FLT3-ITD mutated AML. Blood. 2023;142(Suppl 1):158. doi 10.1182/blood-2023-186699