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

Official title

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

Overview

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).

Interventions

• Drug JNJ-90189892
  JNJ-90189892 will be administered.
• Drug Azacitadine (AZA)
  AZA will be administered.
• Drug Venetoclax (VEN)
  VEN will be administered.

Primary outcome measures

• Number of Participants with Adverse events (AEs) by Severity [Time frame: 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) [Time frame: At least 14 days]

Secondary outcome measures (12)

• Serum Concentration of JNJ-90189892 [Time frame: Up to approximately 2.5 years]
• Area Under the Curve Over a Dosing Interval (AUC tau) of JNJ-90189892 [Time frame: Up to approximately 2.5 years]
• Maximum Observed Plasma Concentration (Cmax) of JNJ-90189892 [Time frame: Up to approximately 2.5 years]
• Minimum Observed Plasma Concentration (Cmin) of JNJ-90189892 [Time frame: Up to approximately 2.5 years]
• Number of Participants with Presence of Anti-JNJ-90189892 Antibodies [Time frame: Up to approximately 2.5 years]
• Complete Response (CR) in Acute Myeloid Leukemia (AML) [Time frame: Up to approximately 2.5 years]
• Overall Response (OR) in Myelodysplastic Neoplasms (MDS) [Time frame: Up to approximately 2.5 years]
• Complete Response in MDS [Time frame: Up to approximately 2.5 years]
• Duration of Response (DOR) [Time frame: Up to approximately 2.5 years]
• Time to Response (TTR) [Time frame: Up to approximately 2.5 years]
• Number of Participants Achieving Transfusion Independence [Time frame: Up to approximately 2.5 years]
• Part 4 Only: Overall Survival (OS) [Time frame: Up to approximately 2.5 years]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Australia · 3 centers

• Concord Hospital — Concord
• Peter MacCallum Cancer Centre — Melbourne
• Sir Charles Gairdner Hospital — Nedlands

France · 3 centers

• Institut Paoli-Calmettes — Marseille
• CHRU de Strasbourg - Hopital de Hautepierre — Strasbourg
• Institut Claudius Regaud — Toulouse

Spain · 3 centers

• Hosp Univ Fund Jimenez Diaz — Madrid
• Clinica Univ. de Navarra — Pamplona
• Hospital Universitario Virgen Rocio — Seville

Identifiers

NCT: NCT06651229 · 90189892AML1001 · 2024-514341-10-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗