First-in-human (FIH) Trial of GEN3018 in Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) or Higher-risk Myelodysplastic Syndrome (HR-MDS)

Official title

An Open-Label, Multicenter, First-in-Human Trial of GEN3018 in Participants With Relapsed or Refractory Acute Myeloid Leukemia or Higher-Risk Myelodysplastic Syndrome

Overview

The drug that will be investigated in the trial is an antibody, GEN3018. Since this is the first trial of GEN3018 in humans, the main purpose is to evaluate safety. In addition to safety, the trial will determine the recommended GEN3018 dose(s) to be tested in a larger group of participants and assess preliminary anti-tumor activity of GEN3018. GEN3018 will be studied in refractory (resistant to treatment) or relapsed (disease has returned) acute myeloid leukemia (also known as R/R AML) and refractory or relapsed higher-risk myelodysplastic syndrome (also known as R/R HR-MDS). The trial consists of 2 parts: 1. Part 1 Dose Escalation will test increasing doses of GEN3018 to identify a safe dose level to be tested in the next part 2. Part 2 Dose Refinement will further test the GEN3018 dose(s) determined from the Dose Escalation. Up to 78 participants may be treated in this trial (up to 60 participants in Part 1; up to 18 participants in Part 2). For an individual participant in the trial, the estimated treatment duration will be up to 1 year. Participation in the trial will require regular scheduled visits to the site. At site visits, there will be various tests (such as blood draws) to monitor whether the treatment is safe and effective. Participants will also be contacted every 3 months after treatment ends to monitor how they are doing. All participants in the trial will receive active drug (ie, GEN3018); no one will be given placebo.

Detailed description

This is a FIH, Phase 1, open-label, multicenter trial in participants with R/R AML or R/R HR-MDS, to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics, and preliminary anti-tumor activity of GEN3018. The trial will be conducted in 2 parts: Dose Escalation (Part 1) and Dose Refinement (Part 2).

Interventions

• Biological GEN3018
  Intravenous (IV) infusion.

Primary outcome measures

• Part 1: Number of Participants with Dose-limiting Toxicities (DLTs) [Time frame: 28 days]
• Parts 1 and 2: Number of Participants with Adverse Events (AEs) [Time frame: Up to approximately 36 months]

Secondary outcome measures (10)

• Parts 1 and 2: Maximum Concentration (Cmax) of GEN3018 [Time frame: Cycle 1 and 2 (each cycle is 28 days)]
• Parts 1 and 2: Time to Cmax (tmax) of GEN3018 [Time frame: Cycle 1 and 2 (each cycle is 28 days)]
• Parts 1 and 2: Predose Trough Concentration (Ctrough) of GEN3018 [Time frame: Cycle 1 and 2 (each cycle is 28 days)]
• Parts 1 and 2: Area Under the Concentration-time Curve from Time 0 to Last Quantifiable Sample (AUClast) of GEN3018 [Time frame: Cycle 1 and 2 (each cycle is 28 days)]
• Parts 1 and 2: Elimination Half-life (t1/2) of GEN3018 [Time frame: Cycle 1 and 2 (each cycle is 28 days)]
• Parts 1 and 2: Clearance (CL) of GEN3018 [Time frame: Cycle1 and 2 (each cycle is 28 days)]
• Parts 1 and 2: Number of Participants with Anti-drug Antibodies (ADAs) Against GEN3018 [Time frame: Up to approximately 1 year]
• Parts 1 and 2: Overall Response Rate (ORR) [Time frame: Up to approximately 1 year]
• Parts 1 and 2: Duration of Response (DOR) [Time frame: Up to approximately 1 year]
• Parts 1 and 2: Time to Response (TTR) [Time frame: Up to approximately 1 year]

Eligibility criteria

Inclusion criteria

All Participants:

• Be at least 18 years of age at the time of signing informed consent form (ICF).
• Participant's life expectancy at screening is judged to be at least 3 months.
• Must have fresh bone marrow samples collected at screening.
• Bone marrow (BM) blasts ≥ 5% at screening.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of ≤ 2.
• Has acceptable laboratory test results during the screening period

Participants with R/R AML:

• Relapsed or refractory AML, either de novo or secondary, and must have failed all conventional therapies.
• Relapsed or refractory to at least one prior line of therapy.

Participants with R/R HR-MDS:

• Diagnosed with high- or very-high risk MDS according to International Prognostic Scoring System (IPSS-R) (score of > 4.5 ie, high or very high) or World Health Organization (WHO) 2022 classification (ie, MDS-IB1 or MDS-IB2).
• Refractory or relapsed after hypomethylating agents (HMAs) (such as azacitidine or decitabine).

Exclusion criteria

All Participants:

• Diagnosis of acute promyelocytic leukemia (APL).
• Presence of extramedullary AML at screening.
• Prior autologous or allogenic hematopoietic stem cell transplant (HSCT) within 3 months prior to initiation of trial treatment.
• Active graft-versus-host disease.
• History of severe immune-related adverse events.
• Treatment with anti-cancer agent (eg, small molecule, antibody, chemotherapy, radiation therapy), or major surgery within 2 weeks prior to the first dose of GEN3018.

Other protocol-defined Inclusion and Exclusion criteria may apply.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 4 centers

• Hospital Universitari Vall d'Hebron — Barcelona
• Hospital Clínic de Barcelona — Barcelona
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Universitari i Politècnic La Fe — Valencia

Denmark · 2 centers

• Aarhus Universitetshospital - Skejby — Aarhus
• Copenhagen Rigshospitalet — Copenhagen

Identifiers

NCT: NCT07384715 · GCT3018-01 · 2025-523101-15-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗