FDA Delays Quizartinib PDUFA Date for Newly Diagnosed FLT3-ITD+ AML


The FDA has pushed back the PDUFA date for quizartinib for select patients with acute myeloid leukemia.

The review period for quizartinib has been extended. The new drug application (NDA) is being considered in combination with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, and as continuation monotherapy following consolidation, for the treatment of newly diagnosed adult patients with FLT3-ITD–positive acute myeloid leukemia (AML).1

The target action date under the Prescription Drug User Fee Act (PDUFA) was extended by 3 months to July 24, 2023, to allow for additional time to review requested updates to the proposed risk evaluation and mitigation strategies included in the NDA. The regulatory agency has not requested any additional efficacy or safety data, according to an announcement from Daiichi Sankyo.

After the FDA granted priority review to the NDA for quizartinib in October 2022, the original PDUFA date was April 24, 2023.2

“We are continuing to work with the FDA to facilitate completion of their review of the quizartinib NDA in order to bring this important medicine to patients as soon as possible,” Mark Rutstein, MD, global head of Oncology Clinical Development at Daiichi Sankyo, stated in a news release. “Quizartinib was shown to improve overall survival [OS] when added to standard chemotherapy and continued as monotherapy and has potential to change the standard of care for patients with newly diagnosed FLT3-ITD–positive AML.”

The NDA was supported by data from the phase 3 QuANTUM-First trial (NCT02668653), which showed that quizartinib plus standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, and continued as monotherapy following consolidation, generated a statistically significant and clinically meaningful improvement in OS vs chemotherapy plus placebo.

Findings presented at the 2022 European Hematology Association Congress demonstrated that at a median follow-up of 39.2 months, patients treated in the quizartinib arm experienced a median OS of 31.9 months (95% CI, 21.0–not estimable [NE]) vs 15.1 months (95% CI, 13.2-26.2) for those given chemotherapy plus placebo, which equated to a 22.4% reduction in the risk of death (HR, 0.776; 95% CI, 0.615-0.979; 2-sided P = .0324).3,4

In the randomized, double-blind, placebo-controlled, global trial, investigators enrolled patients 18 to 75 years of age with newly diagnosed FLT3-ITD–positive AML who had a FLT3-ITD allelic frequency of at least 3%.5 Patients were also required to have an ECOG performance status of 0 to 2, as well as adequate renal and hepatic function.

Key exclusion criteria included a diagnosis of acute promyelocytic leukemia, a diagnosis of AML secondary to prior chemotherapy or radiotherapy for other neoplasms, prior treatment with quizartinib or other FLT3-ITD inhibitors, a history of known central nervous system (CNS) leukemia, or uncontrolled or significant cardiovascular disease. Prior treatment for AML was not allowed, except for leukapheresis, treatment for hyperleukocytosis with hydroxyurea, cranial radiotherapy for CNS leukostasis, prophylactic intrathecal chemotherapy, or growth factor/cytokine support.

Patients began 7+3 chemotherapy during screening, then were randomly assigned 1:1 to receive induction therapy with 40 mg of quizartinib or placebo on days 8 through 21 plus cytarabine on days 1 to 7 and daunorubicin or idarubicin on days 1 to 3 for up to 2 cycles.4 Consolidation consisted of high-dose cytarabine plus quizartinib or placebo and/or allogeneic stem cell transplant, per institutional policies. Quizartinib at 60 mg or placebo monotherapy was given once daily for up to 36 cycles thereafter.

The primary end point was OS. Secondary end points consisted of event-free survival (EFS), complete remission (CR), composite CR (CRc), and safety. Relapse-free survival (RFS) and duration of CR were exploratory end points.

Additional data showed the primary EFS analysis did not produce a statistically significant difference between the 2 study arms (HR, 0.916; 95% CI, 0.754-1.114; P = .2371).

The quizartinib regimen elicited a CRc rate of 71.6% (95% CI, 65.8%-77.0%) vs 64.9% (95% CI, 58.9%-70.6%) for the placebo regimen. The CR rates were 54.9% (95% CI, 48.7%-60.9%) and 55.4% (95% CI, 49.2%-61.4%) for the quizartinib and placebo arms, respectively. CR with incomplete neutrophil or platelet recovery was experienced by 16.8% (95% CI, 12.5%-21.8%) of patients in the quizartinib group compared with 9.6% (95% CI, 6.4%-13.7%) of patients in the placebo group. The median duration of CR in the quizartinib arm was 38.6 months (95% CI, 21.9-NE) vs 12.4 months (95% CI, 8.8-22.7) for the placebo arm.

The median RFS for patients who achieved CR was 39.3 months for quizartinib and 13.6 months for placebo (HR, 0.613; 95% CI, 0.444-0.845).

No new safety signals observed for the quizartinib/chemotherapy regimen. Any-grade treatment-emergent adverse effects (TEAEs) occurred in 99.6% and 98.9% of patients in the quizartinib and placebo arms, respectively. Grade 3 or higher TEAEs were reported in 92.1% and 89.6% of patients, respectively.

The most common grade 3 or higher TEAEs occurring in at least 10% of patients were febrile neutropenia (43.4% and 41.0% in the quizartinib and placebo arms, respectively), neutropenia (18% and 8.6%), hypokalemia (18.9% and 16.4%), and pneumonia (11.7% and 12.7%). Rates of TEAEs associated with fatal outcomes were 11.3% for quizartinib vs 9.7% for chemotherapy alone.


  1. Quizartinib NDA review for patients with newly diagnosed FLT3- ITD positive AML extended by FDA. News release. Daiichi Sankyo. April 20, 2023. Accessed April 21, 2023. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202304/
  2. Quizartinib granted priority review in the U.S. for patients with newly diagnosed FLT3-ITD positive acute myeloid leukemia. News release. Daiichi Sankyo. October 24, 2022. Accessed October 24, 2022. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202210/
  3. Erba H, Montesinos P, Vrhovac R, et al. Quizartinib prolongs survival vs placebo plus intensive induction and consolidation therapy followed by single-agent continuation in patients aged 18-75 years with newly diagnosed FLT3-ITD+ AML. Presented at: 2022 EHA Congress; June 9-12, 2022; Vienna, Austria. Abstract S100.
  4. Quizartinib plus chemotherapy significantly improved overall survival compared to chemotherapy in patients with newly diagnosed FLT3-ITD positive acute myeloid leukemia. News release. Daiichi Sankyo. June 11, 2022. Accessed April 21, 2023. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202206/
  5. Quizartinib with standard of care chemotherapy and as continuation therapy in patients with newly diagnosed FLT3-ITD (+) acute myeloid leukemia (AML) (QuANTUM-First). ClinicalTrials.gov. Updated December 29, 2022. Accessed April 21, 2023. https://clinicaltrials.gov/ct2/show/NCT02668653
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