ZE46-0134-0002-US

Adults (>=18) with relapsed/refractory AML after multiple therapies, molecularly confirmed FLT3 or specified spliceosome mutations (SF3B1/SRSF2/U2AF1/ZRSR2), ECOG <=2, adequate hepatic/renal function

1. Written informed consent before any study-related procedures. 2. Age >=18 years at informed consent. 3. Refractory to or relapsed after multiple AML therapies (with/without HSCT) and exhausted reasonable benefit-expected therapies, unless declined/ineligible. 4. Molecular eligibility: - Group 1: confirmed FLT3-ITD or FLT3-TKD mutation by central laboratory. - Group 2: documented pathogenic SF3B1, SRSF2, U2AF1, or ZRSR2 mutation by local sequencing. 5. Group 1 only: prior gilteritinib exposure with inadequate disease control, or not meeting criteria/declining gilteritinib per investigator judgment. 6. Life expectancy >=3 months (investigator assessment). 7. ECOG performance status <=2. 8. Laboratory eligibility: - AST and ALT <=2.5 x ULN, - Total bilirubin <=1.5 x ULN (or up to 4.0 mg/dL with Gilbert syndrome), - eGFR >40 mL/min (MDRD). 9. Female requirements: - Non-childbearing potential (surgically sterile/postmenopausal) OR - If childbearing potential: negative serum pregnancy test at screening and negative urine pregnancy test on Day 1 pre-dose; no pregnancy attempt/ova donation; protocol contraception through 105 days post-last dose. 10. Male requirements: - Highly effective contraception (2 methods, >=1 barrier) with partner if applicable from screening through 105 days after last dose, - No sperm donation through 105 days after last dose.

Isolated myeloid sarcoma, APL, active CNS AML, leukostasis needing urgent therapy, active uncontrolled HIV/HBV/HCV infection, recent investigational/systemic anti-cancer treatment washout violations, pregnancy/lactation, major uncontrolled cardiac/QTc/comorbidity risks, or inability to comply safely.

1. Isolated myeloid sarcoma without blood/marrow AML involvement. 2. Acute promyelocytic leukemia (FAB M3). 3. Active CNS involvement by AML. 4. Clinical leukostasis requiring urgent therapy. 5. Known active HIV, hepatitis B, or hepatitis C infection (history of HBV/HCV allowed only with negative PCR before treatment). 6. Disseminated intravascular coagulopathy with active unmanageable bleeding or thrombosis signs. 7. Recent investigational agent use within 5 half-lives (or 1 week if half-life unknown). 8. Systemic chemotherapy or radiation within 1 week before protocol treatment start (hydroxyurea allowed for WBC control). 9. Pregnancy or lactation. 10. QTcF >470 msec not correctable with electrolyte/hydration/medication optimization. 11. Psychological/familial/social/geographic/medical/lab factors that preclude informed consent, protocol adherence, safety, or result interpretation. 12. Uncontrolled intercurrent illness, including significant cardiac disease (eg, symptomatic CHF, unstable angina, serious arrhythmia, recent MI with residual abnormalities, NYHA III/IV heart failure, severe ventricular arrhythmias, active ischemia/conduction abnormalities). 13. Uncontrolled infection (controlled infection may be enrolled at investigator discretion).