The purpose of this study is to assess how bleximenib and Venetoclax (VEN)+ Azacitidine
(AZA) works as compared to placebo and VEN+AZA alone for the treatment of participants
with newly diagnosed Acute Myeloid Leukemia (AML) with a mutation in the NPM1 or KMT2A
gene.

A Study of Bleximenib, Venetoclax and Azacitidine For Treatment of Participants With Newly Diagnosed Acute Myeloid Leukemia (AML)

Leukemia, Myeloid, Acute

Acute Myeloid Leukemia

Leukemia

Blood Cancer

Hematologic Neoplasms

Hematologic Malignancies

Hematology

Hematological Malignancies

Placebo

Bleximenib

Venetoclax (VEN)

Azacitidine (AZA)

A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Study of Bleximenib, Venetoclax and Azacitidine for the Treatment of Participants With Newly Diagnosed Acute Myeloid Leukemia Harboring KMT2A Rearrangements or NPM1 Mutations Who Are Ineligible for Intensive Chemotherapy

CR is defined as Bone marrow blasts less than (<) 5 percent (%); Absence of circulating
blasts; Absence of extramedullary disease; Absolute neutrophil count (ANC) greater than
or equal to (>=) 1.0 * 10^9/Liter (1,000/microliter [mcL]); Platelet count >= 100 *
10^9/L (100,000/mcL).

Overall survival time is defined as the time duration from the date of randomization to
death due to any cause.

EFS is defined as the time from randomization to treatment failure, relapse, or death due
to any cause, whichever occurs first.

Duration of CR will be estimated among responders from the date of initial documentation
of CR, to the date of first documented evidence of relapse, or death due to any cause,
whichever occurs first, respectively.

Time to CR is defined as time from randomization to first documented response.

Rate of CR MRD- is defined as percentage of participants who have achieved CR without
MRD.

Transfusion independence is defined as lack of requirement for red blood cell (RBC) and
platelet transfusions during any 56-day period.

Allo-HSCT rate is defined as the percentage of participants who have undergone allo-HSCT
after randomization.

An AE is any untoward medical occurrence in a participant participating in a clinical
study that does not necessarily have a causal relationship with the
pharmaceutical/biological agent under study. Severity will be graded according to the
National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild,
Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related
to adverse event.

Participants with abnormalities in clinical laboratory parameters will be reported.

Serum samples will be analyzed to determine concentrations of bleximenib.

Participants with acute myeloid leukemia (AML) will receive bleximenib in combination
with venetoclax (VEN) and azacitidine (AZA) for 28-days treatment cycles and treatment
will continue until progression or unacceptable toxicity.

Participants with AML will receive placebo in combination with VEN and AZA for 28-days
treatment cycles, and treatment will continue until progression or unacceptable toxicity.

The purpose of this study is to assess how bleximenib and Venetoclax (VEN)+ Azacitidine
(AZA) works as compared to placebo and VEN+AZA alone for the treatment of participants
with Acute Myeloid Leukemia (AML).

A Study of Bleximenib, Venetoclax and Azacitidine For Treatment of Participants With Acute Myeloid Leukemia (AML)

Roswell Park Comprehensive Cancer Center

Gabrail Cancer Center

Providence Portland Medical Center

Thomas Jefferson University

University of Tennessee

Baylor University Medical Center

MD Anderson Cancer Center

Flinders Medical Centre

Royal Prince Alfred Hospital

St George Hospital

Peter MacCallum Cancer Centre

London Health Sciences Centre Victoria Hospital

Princess Margaret Cancer Centre University Health Network

Peking University People s Hospital

Carmel Medical Center

Shaare Zedek Medical Center

Hadassah University Hospita Ein Kerem

Rabin Medical Center

Tel Aviv Sourasky Medical Center

Fukushima Medical University Hospital

Kobe City Medical Center General Hospital

National Hospital Organization Kumamoto Medical Center

Japanese Red Cross Osaka Hospital

Aiiku Hospital

Yamagata University Hospital

University of Fukui Hospital

Kaohsiung Chang Gung Memorial Hospital

Chi Mei Medical Center Liouying Branch

National Taiwan University Hospital

Linkou Chang Gung Memorial Hospital

Ankara University School of Medicine Cebeci Hospital

Memorial Antalya Hospital

Koc University Medical Faculty

Ondokuz Mayis University

Derriford Hospital

CR is defined as Bone marrow blasts less than (<) 5 percent (%); Absence of circulating
blasts; Absence of extramedullary disease; Absolute neutrophil count (ANC) greater than
or equal to (>=) 1.0 * 10^9/Liter (1,000/microliter [mcL] ); Platelet count >= 100 *
10^9/L (100,000/mcL).

Rate of CR-MRD is defined as percentage of participants who have achieved CR-MRD.

Allo-HSCT is defined as the percentage of participants who have undergone allo-HSCT after
randomization.

Participants with acute myeloid leukemia (AML) will receive bleximenib in combination
with venetoclax (VEN) and azacitidine (AZA) for 28-days treatment cycle and treatment
will continue until progression or unacceptable toxicity.

Participants with AML will receive placebo in combination with VEN and AZA for 28-days
treatment cycle, and treatment will continue until progression or unacceptable toxicity.

New York Presbyterian - Weill Cornell

Virginia Commonwealth University - Massey Cancer Center

Wiener Gesundheitsverbund Klinik Hietzing

Ministerio da Saude Instituto Nacional do Cancer

Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)

CIUSSS de l Est de l Ile de Montreal Installation Hopital Maisonneuve Rosemont

TongJi Hospital of TongJi Medical College of Huazhong University of Science & Technology

Azienda Ospedaliera di Perugia Ospedale S.Maria della Misericordia

Ospedale S. Maria Delle Croci

Grande Ospedale Metropolitano 'Bianchi-Melacrino-Morelli' Reggio Calabria

Uniwersyteckie Centrum Kliniczne

Inst. Cat. Doncologia-H Duran I Reynals

Hopital Saint Vincent de Paul

AST Pesaro e Urbino Ospedale San Salvatore

Asan Medical Center

Hosp. San Pedro de Alcantara

Washington University in St Louis

First Affiliated Hospital SooChow University

CHU de Montpellier Hopital Saint Eloi

Queen Mary Hospital

ASST Papa Giovanni XXIII Bergamo

Seoul National University Hospital

Cancer Treatment Center of America Phoenix

Universitair Ziekenhuis Leuven

The First Affiliated Hospital of Guangxi Medical University

CHU d'Angers

CHU de Clermont Ferrand - Site Estaing

Tohoku University Hospital

Uniwersytecki Szpital Kliniczny w Bialymstoku

Hosp. de La Santa Creu I Sant Pau

VM Medical Park Mersin Hospital

The Clatterbridge Cancer Centre

University of Kentucky Markey Cancer Center

Peking University First Hospital

Fakultni Nemocnice Ostrava

Shamir Medical Center Assaf Harofeh

Hosp Univ A Coruna

Chu Helora Hospital La Louviere Site Jolimont

The first Affiliated Hospital of Jilin University

The First Affiliated Hospital of NanChang University

CHRU de Nancy - Hopitaux de Brabois

Kent and Canterbury Hospital

Hosp Clinico Univ de Salamanca

Dartmouth Hitchcock Medical Center

Moffit Cancer center

Norton Cancer Institute

Liga Norte Riograndense Contra O Cancer

General University Hospital of Patras

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Okayama University Hospital

Queen Elizabeth II Health Sciences Centre

Geniko Nosokomeio Thessalonikis George Papanikolaou

Addenbrookes Hospital

Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital

Seoul National University Bundang Hospital

Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital

Guys' and St Thomas' NHS Trust

University of Chicago Medicine

Clinique Saint Pierre

The First Affiliated Hospital of USTC Anhui Provincial Hospital

Uls Santa Maria Hosp. Santa Maria

University Hospitals Sussex NHS Foundation Trust

Klinikum Augsburg

CHU De Nice Hopital De l'Archet

AZ Sint-Jan

The first affiliated hospital of xiamen university

Juravinski Cancer Centre

Cleveland Clinic Florida

Fakultni nemocnice Hradec Kralove

A O U Sant Orsola Malpighi

Casa Sollievo Della Sofferenza IRCCS

University of Rochester Medical Center

Henry Ford Health System

Providence Oncology and Hematology Care Clinic Westside

Swedish Cancer Institute

St Vincents Hospital Melbourne

Ziekenhuis Oost-Limburg

DF Star Rede D or

Real e Benemerita Associacao Portuguesa de Beneficencia

Peking University Third Hospital

Union Hospital Tongji Medical College of Huazhong University of Science and Technology

A Study of Bleximenib, Venetoclax and Azacitidine For Treatment of Participants With Newly Diagnosed Acute Myeloid Leukemia (AML)

Trials at a glance

Trials at a glance

A Study of Bleximenib, Venetoclax and Azacitidine For Treatment of Participants With Newly Diagnosed Acute Myeloid Leukemia (AML)

Outcome measures

Primary outcome measures

Secondary outcome measures