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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Leukemia, Myeloid, Acute; Myelodysplastic Neoplasms
• Intervention / Treatment: Drug: JNJ-90189892; Drug: Azacitadine (AZA); Drug: Venetoclax (VEN)

• Study Type: Interventional
• Enrollment (Estimated): 155
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study1@its.jnj.com

Study Locations

• Australia
  • Concord, Australia, 2139
    • Recruiting
    • Concord Hospital
  • Melbourne, Australia, 3000
    • Recruiting
    • Peter MacCallum Cancer Centre
  • Nedlands, Australia, 6009
    • Recruiting
    • Sir Charles Gairdner Hospital
• France
  • Marseille, France, 13273
    • Recruiting
    • Institut Paoli-Calmettes
  • Strasbourg, France, 67200
    • Recruiting
    • CHRU de Strasbourg - Hopital de Hautepierre
  • Toulouse, France, 31100
    • Recruiting
    • Institut Claudius Regaud
• Spain
  • Madrid, Spain, 28040
    • Recruiting
    • Hosp Univ Fund Jimenez Diaz
  • Pamplona, Spain, 31008
    • Recruiting
    • Clinica Univ. de Navarra
  • Seville, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen Rocio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• A. For Parts 1, 2, and 3: Have a diagnosis, per the world health organization (WHO) 2022 criteria, of (a) Parts 1, 2, and 3: Acute myeloid leukemia (AML) or (b) Parts 1 and 2: Moderate high, high, or very high-risk myelodysplastic neoplasms (MDS) per Molecular International Prognostic Scoring System (IPSS-M); B. For Part 4 only: Previously untreated acute myeloid leukemia (AML) per the WHO 2022 criteria
• Body weight that is greater than or equals to (>=) 40 kg
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Have adequate renal function defined as Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Estimated Glomerular Filtration Rate (eGFR) >=40 milligrams per minute (mL/min) computed with the calculator on the national kidney foundation website
• Participants must have laboratory parameters in the required range

Exclusion Criteria:

• Has a medical history of clinically significant pulmonary compromise, particularly the current need for supplemental oxygen use to maintain adequate oxygenation
• Has evidence of uncontrolled systemic viral, bacterial, or fungal infection. Antimicrobial prophylaxis is permitted
• All participants- Has known allergies, hypersensitivity, or intolerance to JNJ-90189892 or its excipients; Parts 3 and 4- Has known allergies, hypersensitivity, or intolerance to venetoclax (VEN), azacitadine (AZA), or their excipients
• Had major surgery or had significant traumatic injury within 14 days of planned first dose of JNJ-90189892
• Had a prior or concurrent second malignancy with natural history or treatment likely to interfere with any study endpoints of safety or the efficacy of the study treatment
• Has known active central nervous system involvement

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JNJ-90189892: Monotherapy; 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.	Drug: JNJ-90189892; JNJ-90189892 will be administered.
Experimental: JNJ-90189892: In Combination with Azacitadine (AZA)+ Venetoclax (VEN); 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.	Drug: JNJ-90189892; JNJ-90189892 will be administered.; Drug: Azacitadine (AZA); AZA will be administered.; Drug: Venetoclax (VEN); VEN will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse events (AEs) by Severity	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.	From screening untill 30 days after last dose of study drug (that is approximately 2.5 years)
Part 1: Number of Participants with Dose-Limiting Toxicity (DLTs)	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.	At least 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Concentration of JNJ-90189892	Serum samples will be analyzed to determine concentrations of JNJ-90189892.	Up to approximately 2.5 years
Area Under the Curve Over a Dosing Interval (AUC tau) 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.	Up to approximately 2.5 years
Maximum Observed Plasma Concentration (Cmax) of JNJ-90189892	Cmax is the maximum observed plasma concentration of JNJ-90189892. Cmax of JNJ-90189892 will be reported.	Up to approximately 2.5 years
Minimum Observed Plasma Concentration (Cmin) of JNJ-90189892	Cmin is the minimum observed plasma concentration of JNJ-90189892. Cmin of JNJ-90189892 will be reported.	Up to approximately 2.5 years
Number of Participants with Presence of Anti-JNJ-90189892 Antibodies	Participants with presence of anti-JNJ-90189892 antibodies will be reported.	Up to approximately 2.5 years
Complete Response (CR) in Acute Myeloid Leukemia (AML)	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.	Up to approximately 2.5 years
Overall Response (OR) in Myelodysplastic Neoplasms (MDS)	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.	Up to approximately 2.5 years
Complete Response in MDS	CR is achieved when a participant has a best response of CR (including CRh/CRL) according to the IWG 2023 criteria.	Up to approximately 2.5 years
Duration of Response (DOR)	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.	Up to approximately 2.5 years
Time to Response (TTR)	TTR is defined for responders, as the time from the first dose of study drug to first qualifying response.	Up to approximately 2.5 years
Number of Participants Achieving Transfusion Independence	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.	Up to approximately 2.5 years
Part 4 Only: Overall Survival (OS)	OS is defined as the time from the date of first dose of study treatment to the date of death due to any cause.	Up to approximately 2.5 years
Part 4 Only: Event-Free Survival (EFS)	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.	Up to approximately 2.5 years

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2025
• Primary Completion (Estimated): August 5, 2027
• Study Completion (Estimated): November 21, 2028

Study Registration Dates

• First Submitted: October 18, 2024
• First Submitted That Met QC Criteria: October 18, 2024
• First Posted (Actual): October 21, 2024

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; venetoclax
• Other Study ID Numbers: 90189892AML1001 (Janssen Research & Development, LLC); 2024-514341-10-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of Johnson & Johnson Innovative Medicine is available at innovativemedicine.jnj.com/our-innovation/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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes