Neoplasms

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Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

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All Drugs and Chemicals

Cytarabine

Venetoclax

Azacitidine

Daunorubicin

Idarubicin

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Participants with relapsed/refractory AML harboring either NPM1 or KMT2A alterations will receive JNJ-75276617 in combination with either venetoclax (VEN) (Cohort A1: JNJ75276617+VEN) or azacitidine (AZA) (Cohort A2: JNJ-75276617+AZA) or VEN+AZA (Cohort A3: JNJ-75276617+VEN+AZA) to select the recommended phase 2 dose (RP2D) of JNJ-75276617 in combination with VEN, AZA or VEN+AZA (dose selection). In dose expansion portion of the study, participants will receive JNJ-75276617 in combination with AML directed therapies at the RP2D(s).

Participants will receive JNJ-75276617 in combination with VEN+AZA as frontline chemo therapy for newly diagnosed AML participants harboring either KMT2A or NPM1 alterations who are greater than or equal to (\>=)18 years of age to less than (\<) 75 years of age with comorbidities that preclude the use of intensive induction chemotherapy.

Participants will receive combination of JNJ-75276617 with cytarabine+daunorubicin or idarubicin chemotherapy as frontline treatment regimen for participants \>=18 to \<75 years of age with AML harboring either NPM1 or KMT2A alterations and eligible for intensive chemotherapy.

JNJ-75276617

Venetoclax (VEN)

Azacitidine (AZA)

Participants will receive daunorubicin or idarubicin

Daunorubicin or Idarubicin

Study Contact

Janssen Research & Development, LLC Clinical Trial

The purpose of this study is to determine the recommended Phase 2 dose (RP2D) candidate(s) of JNJ-75276617 in combination with AML directed therapies (dose selection) and further to evaluate safety and tolerability of JNJ-75276617 in combination with AML directed therapies at the RP2D(s) (dose expansion).

AML is a heterogenous disease characterized by uncontrolled clonal expansion of hematopoietic progenitor cells (myeloid blasts) in the peripheral blood, bone marrow and other tissues and is the most common type of acute leukemia in adults. 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 aim of this study is to determine the RP2D(s), safety, pharmacokinetic, pharmacodynamic and preliminary clinical activity of JNJ-75276617 in combination with AML directed therapies for adult participants with relapsed/refractory or newly diagnosed AML with NPM1 or KMT2A gene alterations and will include dose selection and subsequent combination specific dose expansion. The total study duration will be up to 2 years. Safety evaluations include adverse events (AE) monitoring, clinical laboratory tests, electrocardiograms (ECGs), vital sign measurements, physical examination findings, and eastern cooperative oncology group (ECOG) performance status score.

A Study of JNJ-75276617 in Combination With Acute Myeloid Leukemia (AML) Directed Therapies

A Phase 1b Study of JNJ-75276617 in Combination With AML-Directed Therapies for Participants With Acute Myeloid Leukemia Harboring KMT2A or NPM1 Alterations

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

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.

Number of Participants with AEs by severity will be reported. 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.

Number of participants with DLT will be reported. The DLTs are specific adverse events and are defined per protocol as any of the following: non-hematologic toxicity, or hematologic toxicity.

Plasma samples will be analyzed to determine concentrations of JNJ-75276617 using a validated, specific, and sensitive method.

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.

Percentage of participants who achieve complete Remission (CR) will be reported. CR is defined as Bone marrow blasts less than (\<) 5 percent (%); Absence of circulating blasts and blasts with Auer rods; Absence of extramedullary disease; Absolute neutrophil count (ANC) greater than or equal to (\>=) 1.0 x 109/Liter (1,000/microliter \[μL\] ); Platelet count \>= 100 x 109/L (100,000/μL).

Percentage of participants who achieve complete remission with partial hematologic recovery (CRh) will be reported. CRh is defined as All criteria of CR with both ANC \>0.5 x 109/L (500/μL) and platelet count \>50 x 109/L (50,000/μL).

Percentage of participants who achieve complete remission with incomplete hematologic recovery (CRi) will be reported. CRi is defined as All CR criteria except for residual neutropenia (\<1.0 x 109/L \[1,000/μL\]) or thrombocytopenia (\<100 x 109/L \[100,000/μL\]).

Percentage of participants who achieve overall response will be reported. Overall response rate (ORR) is defined as the percentage of participants achieving CR, CRh, or CRi.

Duration of response is defined as time from achieving first response of CR, CRh, CRi or overall response to hematologic relapse or death of any cause.

Time to response is defined as time from first dose to achieving the first response of CR, CRh, CRi or overall response.

Janssen Research & Development, LLC

Symptoms and General Pathology

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Precancerous Conditions

1. Lemzoparlimab is administered by intravenous (IV) infusion once a week at a dose of 30 mg/kg in 28-day treatment cycles
2. Azacitidine (AZA): AZA is administered by subcutaneous injection once a day at a dose of 75 mg/m2 on D1 to D7 of each treatment cycle in 28-day treatment cycles.

Lemzoparlimab+Azacitidine (AZA)

AZA is administered by subcutaneous injection once a day at a dose of 75 mg/m2 on D1 to D7 of each treatment cycle in 28-day treatment cycles.

Shuang Li

Yanli Yang, Doctor

Ruixiang Xia, Doctor

Baolin Tang, Doctor

Jian Li, Doctor

Tong Wu, Doctor

Hongmei Jing, Doctor

Shuangnian Xu, Doctor

Xi Zhang, Doctor

Li Wang, Doctor

Quanyi Lu, Doctor

Danian Nie, Doctor

Yanjie He, Doctor

Qifa Liu, Doctor

Jianyu Weng, Doctor

Xin Du, Doctor

Ling Qin, Doctor

Hu Zhou, Doctor

Zhongxing Jiang, Doctor

Zunming Zhu, Doctor

Tiejun Gong, Doctor

Fankai Meng, Doctor

zhichao Chen, Doctor

Zhichao Chen, Doctor

zengmei Sheng, Doctor

Sujun Gao, Doctor

Feng Zhu, Doctor

Fei Li, Doctor

Xiaojing Yan, Doctor

Yi Wang, Doctor

Aili He, Doctor

Ming Hou, Doctor

Wei Wang, Doctor

Zhirong Zhang, Doctor

Qingliang Teng, Doctor

Liangming Ma, Doctor

Sujiang Zhang, Doctor

Xiuqin Wang, Doctor

Hua Zhong, Doctor

Chunkang Chang, Doctor

Yu Wu, Doctor

Xuelei Ma, Doctor

Jin Wei, Doctor

Rong Fu, Doctor

Zhijian Xiao, Doctor

Hongyan Tong, Doctor

Songfu Jiang, Doctor

This phase3 study is a randomized, controlled, open-label, multicenter study to evaluate the efficacy and safety of Lemzoparlimab for injection in combination with AZA versus AZA monotherapy as first-line therapy in treatment-naïve subjects with intermediate- and high-risk MDS.

A Phase 3 Clinical Study to Evaluate Lemzoparlimab for Injection in Combination With Azacitidine (AZA) Versus AZA Monotherapy in Treatment-naïve Patients With Higher-risk Myelodysplastic Syndrome (MDS)

A Randomized, Controlled, Open-label, Multicenter Phase 3 Clinical Study to Evaluate Lemzoparlimab for Injection in Combination With Azacitidine (AZA) Versus AZA Monotherapy in Treatment-naïve Patients With Higher-risk Myelodysplastic Syndrome (MDS)

TJ Biopharma Co., Ltd.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of JNJ-75276617 in Combination With Acute Myeloid Leukemia (AML) Directed Therapies	NCT05453903	Leukemia, Myelo...	JNJ-75276617 Venetoclax (VEN... Azacitidine (AZ... Cytarabine Daunorubicin or...	18 Years -	Janssen Research & Development, LLC
A Phase 3 Clinical Study to Evaluate Lemzoparlimab for Injection in Combination With Azacitidine (AZA) Versus AZA Monotherapy in Treatment-naïve Patients With Higher-risk Myelodysplastic Syndrome (MDS)	NCT05709093	Myelodysplastic...	Lemzoparlimab+A... Azacitidine (AZ...	18 Years -	TJ Biopharma Co., Ltd.
A Study of JNJ-75276617 in Combination With Acute Myeloid Leukemia (AML) Directed Therapies	NCT05453903	Leukemia, Myelo...	JNJ-75276617 Venetoclax (VEN... Azacitidine (AZ... Cytarabine Daunorubicin or...	18 Years -	Janssen Research & Development, LLC

Spots Global Cancer Trial Database for azacitidine (aza)