A Phase 1/2, Open-Label, Dose-Escalation, Dose-Expansion Study of DSP- 5336 in Adult Acute Leukemia Patients with and without Mixed Lineage Leukemia (MLL) Rearrangement or Nucleophosmin 1 (NPM1) Mutation.

Inclusion Criteria

1. Patients in the Phase 1 dose-escalation portion must have a diagnosis of relapsed or

refractory AML, ALL or acute leukemia of ambiguous lineage, as determined by pathology

review at the treating institution, and who failed available standard therapies known

to be active for their AML, ALL, or acute leukemia of ambiguous lineage. Enrollment to

the phase 1 portion of the study may be limited to patients with certain genetic

abnormalities.

Patients in the Phase 2 dose-expansion portion must have a confirmed diagnosis of

relapsed or refractory AML, as determined by pathology review at the treating

institution, and who failed available standard therapies known to be active for their

AML. They must also have a documented KMT2A (MLL)-fusion or NPM1 mutation, which

includes those with coexisting FLT3 genomic alterations and/or IDH1/2 mutations.

2. Be > 18 years of age or 20 years if required by local regulation

3. ECOG < 2

4. WBC below 30,000/μL (hydroxyurea allowed prior to initiation of the study treatment)

5. Clearance of creatinine (CLcr) level ≥ 50 ml/min, assessed by the Cockcroft-Gault

formula

6. Total bilirubin ≤1.5 the upper limit of normal (ULN) (or ≤2.0 ULN for patients with

known Gilbert's syndrome)

7. Aspartate aminotransferase (AST) ≤3.0 times ULN

8. Alanine aminotransferase (ALT) ≤3.0 times ULN

9. Any prior treatment-related toxicities resolved to ≤Grade 1 prior to enrollment, with

the exception of ≤Grade 2 alopecia or neuropathy.

10. Be willing to attend study visits as required by the protocol

11. Have an estimated life expectancy ≥3 months, based on the investigator's assessment

12. Females of childbearing potential must have a negative serum pregnancy test. Females

of childbearing potential are defined as women who have (1) experienced menarche and

have not undergone sterilization procedures (hysterectomy, bilateral tubal ligation,

or bilateral oophorectomy), or have (2) not experienced menopause (defined as having

amenorrhea continuously for more than 12 months that is not determined to be

drug-induced, or who are taking hormone replacement therapy with serum

follicle-stimulating hormone > 35 mlU/ml).

13. Must agree to use a combination of 2 or more different contraception methods (oral

contraceptives/implantable hormonal contraceptives*, and barrier method*) or use

prevention of pregnancy measures (ie, agreement to refrain completely from

heterosexual intercourse) during the study and for 6 months (for females and males

alike) after the last dose of study drug, if male or female patient of child-producing

potential

14. Have AML/ALL material suitable for genomic analysis of AML or ALL genetic alterations

Exclusion Criteria

1. Has a left ventricular ejection fraction (LVEF) <45%, as determined by ECHO

2. Histological diagnosis of acute promyelocytic leukemia

3. Received systemic calcineurin inhibitors within 4 weeks prior to the first dose of DSP

5336

4. Has had abnormal ECGs that are clinically significant, such as QT prolongation (QTc

>450 msec for males and >470 msec for females, with QTc corrected according to

Fridericia's formula [QTcF])

5. Has an active, uncontrolled, bacterial, viral, or fungal infection requiring systemic

therapy

6. Receives concurrent sensitive substrates with a narrow safety window or strong

inhibitors or inducers of CYP3A4/5, including specifically: ketoconazole and

itraconazole. Other antifungals that are used as standard of care to prevent or treat

infections are permitted. If a patient is on one of the excluded azole class

antifungals, he/she can be taken off or switched to a permitted azole 7 or more days

prior to first dose, then the patient could be allowed on study (Arm B) with approval

of the medical monitor.

7. Received immunotherapy, including tumor vaccines and checkpoint inhibitors, within 42

days prior to the first dose of DSP-5336

8. Has been on other investigational treatment within the previous 4 weeks prior to the

first dose of DSP-5336

9. Had major surgery within 28 days prior to the first dose of DSP-5336

10. Has active central nervous system leukemia

11. Previously received menin-MLL inhibitors

12. Has immediately life threatening or severe complications of leukemia

13. Underwent HSCT or chimeric antigen receptor cell (CAR-T) therapy or other modified

T-cell therapy within 60 days prior to the first dose of DSP-5336

14. Received a donor lymphocyte infusion within 28 days prior to the first dose of

DSP-5336, or receiving immunosuppressive therapy post-HSCT at the time of screening,

or with clinically active GVHD or GVHD requiring active medical intervention other

than the use of topical steroids for ongoing cutaneous GVHD

15. Received antineoplastic agents (except hormonal therapies as adjuvant maintenance for

breast or prostate cancers if a patient is taking before starting study treatment, and

hydroxyurea given for controlling blast cells) within 14 days prior to the first dose

of DSP-5336

16. Received anthracycline where cumulative doses exceeded the upper limit per the label

approved in each country or investigator discretion (if there is no label restriction,

investigator must state the cumulative dose received for each patient and sign to

indicate that, in his/her medical opinion, stated prior dose of the agent does not put

patient at undue risk of anthracycline-related cardiotoxicity

17. In the opinion of the treating investigator, have any concurrent conditions that could

pose an undue medical hazard or interfere with interpretation of study results; these

conditions include, but are not limited to: clinically significant non-healing or

healing wounds; concurrent congestive heart failure; concurrent unstable angina;

concurrent cardiac arrhythmia requiring treatment (excluding asymptomatic atrial

fibrillation); recent (within the prior 6 months) myocardial infarction; acute

coronary syndrome within the previous 6 months; significant pulmonary disease

(shortness of breath at rest or on mild exertion), eg, due to concurrent severe

obstructive pulmonary disease, concurrent hypertension not controlled with concomitant

medication, or diabetes mellitus with more than 2 episodes of ketoacidosis in the

prior 6 months

18. Have an active acute or chronic infection, including human immunodeficiency virus

(HIV) as determined by anti-HIV antibodies; and hepatitis B virus (HBV) or hepatitis C

virus (HCV) as determined by hepatitis B surface antigen (HBsAg) or anti-HCV

antibodies, respectively.

For sites in Japan only: Hepatitis B core (HBc) antibody or hepatitis B surface (HBs)

antibody test should be performed if HBsAg is negative. If HBc antibody or HBs

antibody test is positive, HBV DNA quantification test should be performed to confirm

that HBV DNA is negative.

19. Have advanced liver disease or cirrhosis (Child-Pugh's Class B or greater)

20. Have one or more active autoimmune diseases requiring immunosuppressive therapy other

than low-dose corticosteroids (equivalent to prednisone 10mg daily) or azathioprine.

Patients on stable immunomodulatory medications may be considered by the investigator

21. Have active (uncontrolled, metastatic) malignancies of another type

22. Have severe dysphagia, short-gut syndrome, gastroparesis, or other conditions that

limit the ingestion or gastrointestinal absorption of drugs administered orally,

including the inability to swallow oral medication

23. Have cognitive, psychologic, or psychosocial impediment that would impair the ability

of the patient o receive therapy according to the protocol, or adversely affect the

ability of the patient to comply with the informed consent process, protocol, or

protocol-required visits and procedures

24. Are pregnant or breastfeeding or planning to become pregnant Note: Patients who are

breastfeeding may be enrolled if they interrupt breastfeeding prior to the first dose

of any study drugs and do not feed the baby with breast milk expressed after receiving

the first dose of any study drugs. Breastfeeding should not be resumed for at least 6

months after the last dose of study drug

25. Have any history or complication of interstitial lung disease (for sites in Japan

only)

26. Have a history of Torsades de Pointes