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

NCT07384715 | Recruiting Phase 1 DMC

• 2 other identifiers: GCT3018-012025-523101-15-00
• Study Type: interventional
• Target: 78
• Locations: 3 countries
• Sites: 9

Brief Summary

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. 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. 2.Part 2 Dose Refinement will further test the GEN3018 dose(s) determined from the Dose Escalation.

Conditions

R/R AML; R/R HR-MDS; Acute Myeloid Leukemia; Higher-Risk Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

• Part 1: Number of Participants with Dose-limiting Toxicities (DLTs)

  28 days

• Parts 1 and 2: Number of Participants with Adverse Events (AEs)

  Up to approximately 36 months

Secondary Outcomes (10)

• Parts 1 and 2: Maximum Concentration (Cmax) of GEN3018

  Cycle 1 and 2 (each cycle is 28 days)

• Parts 1 and 2: Time to Cmax (tmax) of GEN3018

  Cycle 1 and 2 (each cycle is 28 days)

• Parts 1 and 2: Predose Trough Concentration (Ctrough) of GEN3018

  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

  Cycle 1 and 2 (each cycle is 28 days)

• Parts 1 and 2: Elimination Half-life (t1/2) of GEN3018

  Cycle 1 and 2 (each cycle is 28 days)

Study Arms (1)

GEN3018

EXPERIMENTAL

Participants will receive escalating doses of GEN3018 in Part 1 (Dose Escalation). In Part 2 (Dose Refinement), additional participants may be enrolled to evaluate the safety and preliminary efficacy data of the recommended Part 2 dose(s) as determined from the Part 1 Dose Escalation.

Biological: GEN3018

Interventions

GEN3018 BIOLOGICAL

Intravenous (IV) infusion.

GEN3018

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genmab: lead

Study Sites (9)

Aarhus Universitetshospital - Skejby

Aarhus, 8200, Denmark

RECRUITING

Copenhagen Rigshospitalet

Copenhagen, 2100, Denmark

RECRUITING

Charite Campus Virchow-Klinikum

Berlin, Germany

NOT YET RECRUITING

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, Germany

NOT YET RECRUITING

Klinikum der Universität München Großhadern

Munich, Germany

NOT YET RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

NOT YET RECRUITING

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

NOT YET RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

NOT YET RECRUITING

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

NOT YET RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

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

Study Officials

• Study Official

  Genmab

  STUDY DIRECTOR

Central Study Contacts

Genmab Trial Information

CONTACT

+4570202728; clinicaltrials@genmab.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Randomization will not be used in this trial for Part 1 Dose Escalation, but may be used for Part 2 Dose Refinement.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2026
• First Posted: February 3, 2026
• Study Start: February 16, 2026
• Primary Completion (Estimated): October 18, 2029
• Study Completion (Estimated): April 20, 2030
• Last Updated: May 7, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3); ES (4); DK (2)