First-in-Human Dose Escalation Study of AFM28 in Patients With Relapsed/Refractory Acute Myeloid Leukemia

NCT05817058 | Terminated Phase 1 DMC

• 1 other identifier: AFM28-101
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 5

Brief Summary

This study is a First In Human, phase 1, open-label, non-randomized, multi-center, multiple ascending dose escalation study evaluating AFM28 as a monotherapy in subjects with Relapsed/Refractory CD123-positive Acute Myeloid Leukemia (AML). AFM28 is a tetravalent monoclonal antibody targeting the interleukin-3 receptor subunit alpha (IL3RA, CD123) and the low affinity immunoglobulin gamma Fc region receptor III-A (FCGR3A, CD16A). It is developed as an antineoplastic agent for hematologic malignancies known to express CD123. The primary pharmacological Mode of Action of AFM28 is induction of cell death of CD123-expressing cells by stimulating Antibody-Dependent Cell-mediated Cytotoxicity mediated by CD16A-expressing immune cells, primarily Natural Killer cells. The aim of the dose escalation is to determine the Maximum Tolerated Dose (MTD) and/or establish one or more Recommended Phase 2 Doses, based on safety, preliminary anti-leukemic activity and Pharmacokinetics / Pharmacodynamics data.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• The Incidence of dose limiting toxicities

  The incidence of dose limiting toxicities during dose limiting toxicities observation period considering the totality of treatment-emergent adverse events is evaluated using * National Cancer Institute Common Terminology Criteria for Adverse Events, v5.0 * the American Society of Transplantation and Cellular Therapy Cytokine Release Syndrome grading system for Cytokine Release Syndrome * the Cairo-Bishop Tumor Lysing Syndrom (TLS) grading system for TLS

  28 days following the first dose of study treatment

Secondary Outcomes (14)

• Incidence and severity of Treatment Emergent Adverse Events

  through study completion (up to 36 weeks)

• Incidence and severity of Serious Adverse Events

  through study completion (up to 36 weeks)

• Incidence of subjects developing anti-drug antibodies

  through study completion (up to 36 weeks)

• Area under the concentration-time curve

  cycle 1 (day 1 and day 28)

• Cmax

  cycle 1 (day 1 and day 28)

Study Arms (1)

Treatment of escalating doses of AFM28

EXPERIMENTAL

AFM28 first in human starting dose will be 25 mg i.v.

Drug: AFM28

Interventions

AFM28 DRUG

AFM28 dose escalation

Treatment of escalating doses of AFM28

Eligibility Criteria

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

You may qualify if:

• \. Subjects with a confirmed diagnosis of AML as defined by 2016 WHO Classification and determined by pathology review at the study site. Subjects with acute promyelocytic leukemia are excluded.
• \. Subjects must have CD123-positive AML confirmed on bone marrow or peripheral blood at Screening (assessed locally without any cut-off level).
• \. Subjects with AML who are in the first, second, or third relapse OR who are at least primary refractory and received at most 3 regimes of previous standard anti-leukemia therapy.
• \. Primary refractory is defined as ≥ 5% blasts in bone marrow following 2 cycles of anthracycline and cytarabine based induction (such as 3+7 or similar), or one cycle of purine analogue containing induction, or after ≥ 3 cycles hypomethylating agent ± or low dose cytarabine ± B-Cell lymphoma 2 based induction regimen, or ≥ 4 cycles of hypomethylating agent based therapy.
• \. Subjects with prior autologous and allogeneic bone marrow transplant are eligible. Subjects with an allogeneic transplant must meet the following conditions: The transplant must have been performed \> 3 months before the date of dosing on this study, the subject must not have active graft versus host disease, must be off all graft versus host disease medications at least \> 28 days prior to date of dosing of study drug (for example, calcineurin inhibitors, ≥ 10 mg/day prednisone or other steroid equivalent, or other immunosuppressive agents).

You may not qualify if:

• \. Diagnosis of BCR-ABL-positive leukemia, acute promyelocytic leukemia, or juvenile myelomonocytic leukemia.
• \. Known hypersensitivity/allergic reaction ≥ grade 3 to monoclonal antibodies or any components used in the AFM28 drug product preparation, any history of anaphylaxis or uncontrolled asthma. Prior CD123 targeting therapies should be allowed after discussion with and at the discretion of the Sponsor.
• \. Received any anticancer therapy or investigational treatment for AML within 14 days of the first dose of study drug and within 28 days for biological agents including but not limited to monoclonal antibodies, cellular therapies, bispecific antibodies, checkpoint antibodies and others. Must have recovered to grade ≤ 1 from any grade 2 to 4 toxicity from previous treatment, except alopecia.
• \. History of any other systemic malignancy, unless previously treated with curative intent and the subject has been disease free for 2 years or longer. Examples for acceptable previous malignancies include completely removed in situ cervical intra-epithelial neoplasia, non-melanoma skin cancer, ductal carcinoma in situ, early-stage prostate cancer that has been adequately treated. Subjects who meet the above criteria and are on maintenance therapy for the prior malignancy may be eligible after discussion and approval from the medical monitor.
• \. The subject has received radionuclide treatment within 6 weeks of the first dose of study treatment.
• \. Known clinically active or suspected central nervous system (CNS) leukemia. If suspected, CNS leukemia should be ruled out with relevant imaging and/or examination of cerebrospinal fluid. Subjects with known prior CNS leukemia should have had at least two consecutive negative Lumbar Punctures for CNS leukemia and no clinical signs.

Sponsors & Collaborators

• Affimed GmbH: lead

Study Sites (5)

Institut Universitaire du Cancer Toulouse - Oncopole

Toulouse, 31059, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Institut Català d'Oncologia-Hospital Duran i Reynals

Barcelona, 08907, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, CP 46026, Spain

Location

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

• Lydia Wunderle

  Affimed GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2023
• First Posted: April 18, 2023
• Study Start: March 21, 2023
• Primary Completion: November 28, 2024
• Study Completion: June 13, 2025
• Last Updated: July 23, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2); ES (3)