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.

A Phase 1/2 Study of Bleximenib in Participants With Acute Leukemia (cAMeLot-1)

Acute Leukemia

Bleximenib

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

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.

Percentage of participants with DLT will be assessed accordingly to national cancer institute common terminology criteria for adverse events (NCI-CTCAE) version 5.

Rate of CR/CRh is defined as the percentage of participants achieving a CR or CRh at any time post-treatment.

Plasma concentration of bleximenib will be reported.

ORR is defined as the percentage of participants who achieve any response.

DOR will be calculated among responders from the date of initial documentation of a response to the date of first documented evidence of relapse, as defined in the disease-specific response criteria, or death due to any cause, whichever occurs first.

TTR is defined for the responders as the time from the date of the first dose of bleximenib to the date of the first documented response.

The duration of CR/CRh is defined from the date of first CR or CRh response achieved to the date of first evidence of relapsed disease or death due to any cause, whichever occurs first, for participants who achieve a CR or CRh.

Time to CR/CRh is defined for responders as the time from the date of the first dose of bleximenib to the date of first achieving either CR or CRh, depending on which milestone is reached.

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

OS is defined from the date of first dose of study treatment to the date of death due to any cause.

MRD-negative rate is defined as the percentage of participants who are MRD-negative at any timepoint after the first dose of bleximenib in the responders.

An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. A Serious AE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Transfusion independence is defined as independence from red blood cells (RBC) and platelet transfusions during any 56-day interval after receiving study treatment.

Participants in Phase 1 Part 1 (dose escalation) will receive bleximenib orally. The dose levels will be escalated based on the dose limiting toxicities (DLT) evaluation by Study Evaluation Team (SET) until the recommended Phase 2 Doses (RP2Ds) have been identified. Participants in Phase 1 Part 2 (dose expansion) will receive bleximenib orally at the RP2D(s) determined in Part 1. In Phase 2 participants will receive bleximenib at the RP2D to evaluate anti-leukemia activity and demonstrate acceptable safety at the RP2D(s).

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).

A Study of JNJ-75276617 in Participants With Acute Leukemia

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by uncontrolled clonal
      expansion of hematopoietic progenitor cells (myeloid blasts) in the peripheral blood, bone
      marrow, and other tissues. Acute lymphoblastic leukemia (ALL) is a hematologic malignancy
      propagated by impaired differentiation, proliferation, and accumulation of lymphoid
      progenitor cells in the bone marrow and/or extramedullary sites. JNJ-75276617 is an orally
      bioavailable, potent, and selective protein-protein interaction inhibitor of the binding
      between histone-lysine N-methyltransferase 2A ([KMT2A], also called mixed-lineage leukemia 1
      [MLL1]; wild-type and fusion) and menin, with activity in leukemic cell lines and primary
      leukemia patient or patient-derived samples with either KMT2A alterations including gene
      rearrangements (KMT2A-r), duplications, and amplification, or nucleophosmin 1 gene (NPM1)
      alterations. The primary goal of this FIH study is to establish the recommended Phase 2 dose
      (RP2D) of JNJ-75276617 with an acceptable safety profile. The total duration of the study is
      up to 2 years and 10 months. Safety assessment will include adverse events (AEs), serious
      adverse events (SAEs), physical examination, Eastern Cooperative Oncology Group (ECOG)
      performance status, vital signs, electrocardiogram, clinical safety laboratory assessment and
      pregnancy testing.

City of Hope

University of California Irvine Medical Center

University of California San Francisco

Norton Cancer Institute

Massachusetts General Hospital

Dana Farber Cancer Institute

NYU Langone Medical Center

MD Anderson

Medical College of WI at Froedtert

Monash Medical Centre

Royal Perth Hospital

Gold Coast University Hospital

Institut Paoli Calmettes

CHU de Nantes hotel-Dieu

Centre Hospitalier Universitaire (CHU) de Bordeaux Hopital HautLeveque Centre Francois Magendie

Institut Universitaire du Cancer Toulouse Oncopole

CHU Bretonneau

Hosp. Univ. Vall D Hebron

Hosp. Clinic I Provincial de Barcelona

Hosp. Univ. Fund. Jimenez Diaz

Clinica Univ. de Navarra

Guy's and St Thomas' NHS Foundation Trust

The Christie Nhs Foundation Trust

Oxford University Hospitals NHS Trust

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

Percentage of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.

Plasma concentration of JNJ-75276617 will be reported.

Number of participants with depletion of leukemic blasts will be reported.

Number of participants with differentiation of leukemic blasts will be reported.

Changes in expression of menin-KMT2A target genes will be reported.

ORR is defined as the percentage of participants who achieve complete remission (CR), CR with incomplete hematologic recovery (CRi) and CR with partial hematologic recovery (CRh).

TTR is defined for the responders as the time from the date of the first dose of JNJ-75276617 to the date of the first documented response.

Participants in Part 1 (dose escalation) will receive JNJ-75276617 orally on a 28-day cycle. The dose levels will be escalated based on the dose limiting toxicities (DLT) evaluation by Study Evaluation Team (SET) until the recommended Phase 2 Doses (RP2Ds) has been identified. Participants in Part 2 (dose expansion) will receive JNJ-75276617 orally at one of the RP2D(s) determined in Part 1. Food effect cohort (optional) participants will receive JNJ-75276617 orally on Cycle 2 Day 1 under fasted condition and on Cycle 2 Day 2 under fed condition.

Hopital Saint Louis

UCSF Benioff Children's Hospital

University of Chicago

St Francis Hospital & Health Centers Indiana Blood and Marrow Transplantation

Karmanos Cancer Institute

University of New Mexico

Roswell Park Comprehensive Cancer Center

Montefiore Medical Center

Start Midwest

Fox Chase Cancer Center

Maine Health

University of Tennessee Medical Center

Baylor University Medical Center

Houston Methodist Hospital

Swedish Cancer Institute

San Antonio Methodist TX Transplant Physicians Group

Virginia Commonwealth University

Peking University First Hospital

Qilu Hospital of Shandong University

Ghent University Hospital

Fundacao Faculdade de Medicina Instituto do Cancer do Estado de Sao Paulo

Fundacao Antonio Prudente A C Camargo Cancer Center

Vancouver Coastal Health

The First Affiliated Hospital of NanChang University

The First Affiliated Hospital of Wenzhou Medical University

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

Henan Cancer Hospital

Hopital Jean Minjoz

CHU de Nantes hotel Dieu

CHU Lyon Sud

Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre

CHRU Nancy Brabois

Carmel Medical Center

Hadassah University Hospita Ein Kerem

Tel Aviv Sourasky Medical Center

Kyushu University Hospital

Fukushima Medical University Hospital

Kanazawa University Hospital

Gunmaken Saiseikai Maebashi Hospital

Hokkaido University Hospital

NTT Medical Center Tokyo

Yamagata University Hospital

University of Fukui Hospital

Seoul National University Hospital

Asan Medical Center

Samsung Medical Center

Hosp Univ Vall D Hebron

Hosp Clinic de Barcelona

Hosp. Gral. Univ. Gregorio Maranon

Hospital Infantil Universitario Nino Jesus

Hosp Univ Fund Jimenez Diaz

Hosp. Clinico Univ. de Valencia

China Medical University Hospital

National Cheng Kung University Hospital

National Taiwan University Hospital

University Hospital of Wales

Leeds Teaching Hospitals NHS Trust

The Clatterbridge Cancer Centre

Guys and St Thomas NHS Foundation Trust

University College London Hospitals

The First Hospital of Jilin University

Nanfang Hospital of Southern Medical Hospital

First Affiliated Hospital Medical School of Zhejiang University

Gustave Roussy

Hosp Clinico Univ de Salamanca

Hosp. Virgen Del Rocio

University Hospitals Plymouth NHS Trust

Oregon Health And Science University

Ministerio da Saude Instituto Nacional do Cancer

Instituto D Or de Pesquisa e Ensino

Liga Norte Riograndense Contra O Cancer

Instituto D Or de Pesquisa e Ensino IDOR

Princess Margaret Cancer Centre University Health Network

Hopital Maisonneuve Rosemont

Institute of Hematology and Blood Diseases Hospital

Zhongda Hospital Southeast University

Hopital trousseau- APHP

CHRU de Nancy - Hopitaux de Brabois

Sheba Medical Center

National Cancer Center Hospital East

Kobe City Medical Center General Hospital

A Phase 1/2 Study of Bleximenib in Participants With Acute Leukemia (cAMeLot-1)

Trials at a glance

Trials at a glance

A Phase 1/2 Study of Bleximenib in Participants With Acute Leukemia (cAMeLot-1)

Outcome measures

Primary outcome measures

Secondary outcome measures