A First in Human Study of the Menin-KMT2A (MLL1) Inhibitor JNJ-75276617 in Participants with Acute Leukemia

The purpose of this study is to determine the recommended Phase 2 dose(s) (RP2D[s]) of
JNJ-75276617 in Part 1 (Dose Escalation) and to determine safety and tolerability at the
RP2D(s) in Part 2 (Dose Expansion).

Inclusion Criteria:

- Relapsed or refractory acute leukemia and has exhausted, or is ineligible for,
available therapeutic options

- Acute leukemia harboring histone-lysine N-methyltransferase 2A (KMT2A), nucleophosmin
1 gene (NPM1) or nucleoporin 98 gene or nucleoporin 214 gene (NUP98 or NUP214)
alterations

- Pretreatment clinical laboratory values meeting the following criteria: (a)
Hematology: white blood cell (WBC) count less than or equal to (<=) 20 * 10^9/liter
(L) (hydroxyurea may be used to lower WBC count at screening and during study;
cytoreductive therapy may be considered with sponsor approval; (b) Chemistry:
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=2.5 * upper
limit of normal (ULN), total serum bilirubin <= 1.5 * ULN (participants with elevated
bilirubinemia, such as Gilbert's syndrome, may enroll if conjugated bilirubin is
within clinically acceptable range) and renal function; Estimated or measured
glomerular filtration rate greater than or equal to (>=) 50 milliliter per minute
(mL/min)/1.73 meter square (m^2) per four variable modified diet in renal disease
(MDRD) equation

- Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1.
Adolescent participants only: Performance status >=70 by Lansky scale (for
participants less than [<]16 years of age) or >=70 Karnofsky scale (for participants
>=16 years of age)

- A participant of childbearing potential must have a negative highly sensitive serum
beta-human chorionic gonadotropin at screening and within 48 hours prior to the first
dose of study treatment

- A participant must agree to all the following during the study and for 90 days after
the last dose of study treatment: (a) wear a condom when engaging in any activity that
allows for passage of ejaculate to another person; (b) not to donate sperm or freeze
for future use for the purpose of reproduction. In addition, the participant should be
advised of the benefit for a female partner to use a highly effective method of
contraception as condom may break or leak

Exclusion Criteria:

- Acute promyelocytic leukemia, diagnosis of Down syndrome associated leukemia or
juvenile myelomonocytic leukemia according to World Health Organization (WHO) 2016
criteria

- Active central nervous system (CNS) disease

- Prior solid organ transplantation

- QTc according to Fridericia's formula (QTcF) for males >= 450 millisecond (msec) or
for females >= 470 msec. Participants with a family history of Long QT syndrome are
excluded

- Exclusion criteria related to stem cell transplant: a. Willing and able to undergo
allogeneic stem cell transplant (if clinically indicated); b. Received prior treatment
with allogenic bone marrow or stem cell transplant <=3 months before the first dose of
study treatment; c. Has evidence of graft versus host disease; d. Received donor
lymphocyte infusion <=1 month before the first dose of study treatment; e. Requires
immunosuppressant therapy (exception: daily doses <=10 milligrams (mg) prednisone or
equivalent are allowed for adrenal replacement)

- Prior cancer immunotherapy within 4 weeks prior to enrollment or blinatumomab within 2
weeks prior to enrollment. Additional prior cancer therapies must not be given within
4 weeks prior to enrollment or 5 half-lives of the agent (whichever is shorter)