Leukemia, Myeloid, Acute

The purpose of Part 1 (Dose Escalation) of the study is to assess the effective dose (recommended Phase 2 dose[s] [RP2Ds]) that can be safely administered, and dosing regimens of JNJ-90189892 in participants with relapsed or refractory (R/R) acute myeloid leukemia (AML) or R/R higher-risk type of myelodysplastic neoplasms (MDS [type of cancer of the blood and bone marrow, which does not respond to treatment or comes back after treatment]). The purpose of Part 2 (Cohort Expansion) is to further assess the safety, tolerability and efficacy in participants with R/R AML or higher-risk types of MDS at the RP2D regimen(s). The purpose of Part 3 and 4 is to assess the effective dose (recommended Phase 2 combination dose [RP2CD]) that can be safely administered, and dosing regimens of JNJ-90189892 in combination with azacitadine (AZA) + venetoclax (VEN) in participants with R/R AML (part 3) and newly diagnosed (ND) AML (part 4).

A Study of JNJ-90189892 for Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Neoplasms

Acute Myeloid Leukemia

Leukemia

Blood Cancer

Hematologic Neoplasms

Hematologic Malignancies

Hematology

Hematological Malignancies

Myelodysplastic Neoplasms

Venetoclax (VEN)

JNJ-90189892

Azacitadine (AZA)

A Phase 1, First-in-Human, Dose Escalation Study of JNJ-90189892 for Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Neoplasms

An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. 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, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.

DLT is defined as any toxicity that requires discontinuation of treatment, any Grade 5 toxicity; Non-hematologic toxicity (Grade 3 or 4) and Hematologic toxicity.

Serum samples will be analyzed to determine concentrations of JNJ-90189892.

AUC tau is the total observed plasma concentration of JNJ-90189892 in the body during the time between doses. AUCtau of JNJ-90189892 will be reported.

Cmax is the maximum observed plasma concentration of JNJ-90189892. Cmax of JNJ-90189892 will be reported.

Cmin is the minimum observed plasma concentration of JNJ-90189892. Cmin of JNJ-90189892 will be reported.

Participants with presence of anti-JNJ-90189892 antibodies will be reported.

CR is achieved when a participant has a best response of CR (including complete response with partial hematologic recovery [CRh] or complete response with incomplete hematologic recovery [CRi]) according to the European Leukemia Network (ENL) 2022 criteria.

OR is achieved when a participant with MDS has a CR (any type, that is CRh or complete response with limited count recovery [CRL]), partial response (PR), or hematologic improvement (HI) according to the International Working Group (IWG) 2023 criteria.

CR is achieved when a participant has a best response of CR (including CRh/CRL) according to the IWG 2023 criteria.

DOR is defined for responsders only, as time from date of initial documentation of a response to the first documented evidence of no reponse, disease progression, relapse, initation of a new systemic anti-cancer therapy (besides hematopoietic stem cell transplant [HSCT]), or death, whichever comes first.

TTR is defined for responders, as the time from the first dose of study drug to first qualifying response.

Transfusion independence is defined as the absence of red blood cell (RBC) and platelet transfusions for 8 weeks or longer after starting study treatment for participants with AML and 16 weeks or longer for participants with MDS.

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

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

Participants will receive JNJ-90189892 in Part 1 (Dose escalation) of the study and the dose levels will be escalated sequentially based on the decisions of the study evaluation team (SET) until the recommended phase 2 dose (RP2D) has been identified. Participants in Part 2 (Dose expansion) will receive JNJ-90189892 at the RP2D determined in Part 1.

Participants with relapsed or refractory (R/R) acute myeloid leukemia (AML) in Part 3 will receive JNJ-90189892+ AZA+VEN to determine the recommended Phase 2 combination dose (RP2CD). The starting JNJ-90189892 dose regimen in Part 3 will be at least 1 dose level below the highest dose level cleared in Part 1 as determined by the SET. In Part 4 participants with newly diagnosed (ND) AML will receive JNJ-90189892+ AZA+VEN starting from the JNJ-90189892 dose level determined safe in Part 3 by the SET.

The purpose of Part 1 (Dose Escalation) of the study is to assess the effective dose
(recommended Phase 2 dose[s] [RP2Ds]) that can be safely administered, and dosing
regimens of JNJ-90189892 in participants with relapsed or refractory (R/R) acute myeloid
leukemia (AML) or R/R higher-risk type of myelodysplastic neoplasms (type of cancer of
the blood and bone marrow, which does not respond to treatment or comes back after
treatment). The purpose of Part 2 (Cohort Expansion) is to further assess the safety,
tolerability and efficacy in participants with R/R AML or higher-risk types of MDS.

Concord Hospital

Peter MacCallum Cancer Centre

Sir Charles Gairdner Hospital

Institut de Cancerologie Strasbourg Europe ICANS

Institut Claudius Regaud

Hosp Univ Fund Jimenez Diaz

Clinica Univ. de Navarra

Hospital Universitario Virgen Rocio

An AE is any untoward medical occurrence in a clinical study participant administered a
pharmaceutical (investigational or non-investigational) product. An AE does not
necessarily have a causal relationship with the intervention. 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, Grade 2= Moderate,
Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.

DLT is defined as any toxicity that requires discontinuation of treatment, any Grade 5
toxicity; Non-hematologic toxicity (Grade 3 or 4) and Hematologic toxicity.

AUC tau is the total observed plasma concentration of JNJ-90189892 in the body during the
time between doses. AUCtau of JNJ-90189892 will be reported.

Cmax is the maximum observed plasma concentration of JNJ-90189892. Cmax of JNJ-90189892
will be reported.

Cmin is the minimum observed plasma concentration of JNJ-90189892. Cmin of JNJ-90189892
will be reported.

CR is achieved when a participant has a best response of CR (including complete response
with partial hematologic recovery [CRh] or complete response with incomplete hematologic
recovery [CRi]) according to the European Leukemia Network (ENL) 2022 criteria.

OR is achieved when a participant with MDS has a CR (any type, that is CRh or complete
response with limited count recovery [CRL]), partial response (PR), or hematologic
improvement (HI) according to the International Working Group (IWG) 2023 criteria.

CR is achieved when a participant has a best response of CR (including CRh/CRL) according
to the IWG 2023 criteria.

DOR is defined for responsders only, as time from date of initial documentation of a
response to the first documented evidence of no reponse, disease progression, relapse,
initation of a new systemic anti-cancer therapy (besides hematopoietic stem cell
transplant [HSCT]), or death, whichever comes first.

TTR is defined for responders, as the time from the first dose of study drug to first
qualifying response.

Transfusion independence is defined as the absence of red blood cell (RBC) and platelet
transfusions for 8 weeks or longer after starting study treatment for participants with
AML and 16 weeks or longer for participants with MDS.

Participants will receive JNJ-90189892 in Part 1 (Dose escalation) of the study and the
dose levels will be escalated sequentially based on the decisions of the study evaluation
team (SET) until the recommended phase 2 dose (RP2D) has been identified. Participants in
Part 2 (Dose expansion) will receive JNJ-90189892 at the RP2D determined in Part 1.

A Study of JNJ-90189892 for Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Neoplasms

Trials at a glance

Trials at a glance