A Phase 1/2, First in Human Study of the Menin-KMT2A (MLL1) Inhibitor BLEXIMENIB in Participants with Acute Leukemia

The purpose of this study is to determine the recommended Phase 2 dose(s) (RP2D[s]) of
bleximenib in phase 1 Part 1 (Dose Escalation) and to determine the safety and
tolerability at RP2D in Phase 1 Part 2 (Dose expansion). The purpose of the Phase 2 part
of the study is to evaluate the efficacy of bleximenib at the RP2D.

Inclusion Criteria:

Phase 1:

- Age 2 years and above (pediatric cohort only), all other cohorts 18 years and above

- Relapsed or refractory (R/R) 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

Phase: 2

- Participants greater than 18 years are eligible

- Must have had an initial diagnosis of acute myeloid leukemia (AML) per the WHO 2022
classification criteria and have relapsed/refractory disease

- AML harboring KMT2A-r (gene rearrangement/translocation) or NPM1 mutations only

For Both Phase 1 and 2:

- 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) and (b) renal function; For adult participants, estimated or measured glomerular
filtration rate greater than equal (>=) 30 milliliter per minute (mL/min) per four
variable MDRD equation. For pediatric participants an estimated or measured
glomerular filtration rate >50 mL/min per the CKiD (Chronic Kidney Disease in
Children) Schwartz formula

- Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2.
Pediatric 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 female 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

- Participant must agree to all protocol required contraception requirements and avoid
sperm or egg donations or freezing for future reproductive use while on study and
for 90 days (males) or 6 months (females) after the last dose of study treatment

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. Received prior treatment with
allogenic bone marrow or stem cell transplant <=3 months before the first dose of
study treatment; b. Has evidence of graft versus host disease; c. Received donor
lymphocyte infusion <=1 month before the first dose of study treatment; d. 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)