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

NCT06651229 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 90189892AML10012024-514341-10-00
• Study Type: interventional
• Target: 155
• Locations: 3 countries
• Sites: 9

Brief Summary

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).

Conditions

Myelodysplastic Neoplasms; Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (13)

• Serum Concentration of JNJ-90189892

  Up to approximately 2.5 years

• Area Under the Curve Over a Dosing Interval (AUC tau) of JNJ-90189892

  Up to approximately 2.5 years

• Maximum Observed Plasma Concentration (Cmax) of JNJ-90189892

  Up to approximately 2.5 years

• Minimum Observed Plasma Concentration (Cmin) of JNJ-90189892

  Up to approximately 2.5 years

• Number of Participants with Presence of Anti-JNJ-90189892 Antibodies

  Up to approximately 2.5 years

Study Arms (2)

JNJ-90189892: Monotherapy

EXPERIMENTAL

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: In Combination with Azacitadine (AZA)+ Venetoclax (VEN)

EXPERIMENTAL

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; Drug: Azacitadine (AZA); Drug: Venetoclax (VEN)

Interventions

Azacitadine (AZA) DRUG

AZA will be administered.

JNJ-90189892: In Combination with Azacitadine (AZA)+ Venetoclax (VEN)

Venetoclax (VEN) DRUG

VEN will be administered.

JNJ-90189892: In Combination with Azacitadine (AZA)+ Venetoclax (VEN)

JNJ-90189892 DRUG

JNJ-90189892 will be administered.

JNJ-90189892: In Combination with Azacitadine (AZA)+ Venetoclax (VEN); JNJ-90189892: Monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (9)

Concord Hospital

Concord, 2139, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, 3000, Australia

RECRUITING

Sir Charles Gairdner Hospital

Nedlands, 6009, Australia

RECRUITING

Institut Paoli-Calmettes

Marseille, 13273, France

RECRUITING

Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre

Strasbourg, 67200, France

RECRUITING

Institut Claudius Regaud

Toulouse, 31100, France

RECRUITING

Hosp Univ Fund Jimenez Diaz

Madrid, 28040, Spain

RECRUITING

Clinica Univ. de Navarra

Pamplona, 31008, Spain

RECRUITING

Hospital Universitario Virgen Rocio

Seville, 41013, Spain

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Central Study Contacts

Study Contact

CONTACT

844-434-4210; Participate-In-This-Study1@its.jnj.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2024
• First Posted: October 21, 2024
• Study Start: March 21, 2025
• Primary Completion (Estimated): August 5, 2027
• Study Completion (Estimated): November 21, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

FR (3); ES (3); AU (3)