Testing AFM28 for patients with relapsed or refractory acute myeloid leukemia

A Phase 1 Multicenter, Open Label, First-in-Human Dose Escalation Study of AFM28, a Bispecific ICE® That Targets CD123 and CD16A, in Patients With CD123-Positive Relapsed/Refractory Acute Myeloid Leukemia

This study is testing a new drug called AFM28 to see if it can help people with relapsed or hard-to-treat acute myeloid leukemia feel better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Affimed GmbH (Industry-sponsored)
• Drugs / interventions: prednisone
• Locations: 6 sites (Copenhagen and 5 other locations)
• Trial ID: NCT05817058 on ClinicalTrials.gov

What this trial studies

This is a first-in-human, phase 1, open-label study evaluating the safety and efficacy of AFM28, a monoclonal antibody, in patients with relapsed or refractory CD123-positive acute myeloid leukemia (AML). The study involves multiple ascending doses of AFM28 administered intravenously to determine the maximum tolerated dose and assess preliminary anti-leukemic activity. Participants will receive treatment weekly until disease progression or other discontinuation criteria are met, with safety monitored by a review committee. The study aims to gather pharmacokinetics and pharmacodynamics data to inform future dosing decisions.

Who should consider this trial

Good fit: Ideal candidates include adults with confirmed CD123-positive relapsed or refractory acute myeloid leukemia who have received limited prior therapies.

Not a fit: Patients with acute promyelocytic leukemia or those who have not been previously treated for AML may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat acute myeloid leukemia.

How similar studies have performed: Other studies targeting CD123 in acute myeloid leukemia have shown promise, indicating potential for success with this approach.

Eligibility criteria

Inclusion Criteria:

* 1. 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.

  2. Subjects must have CD123-positive AML confirmed on bone marrow or peripheral blood at Screening (assessed locally without any cut-off level).

  3. 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.

  4. 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.

  5. 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).

Exclusion Criteria:

* 1. Diagnosis of BCR-ABL-positive leukemia, acute promyelocytic leukemia, or juvenile myelomonocytic leukemia.

  2. 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.

  3. 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.

  4. 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.

  5. The subject has received radionuclide treatment within 6 weeks of the first dose of study treatment.

  6. 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.

Where this trial is running

Copenhagen and 5 other locations

• Rigshospitalet — Copenhagen, Denmark (Withdrawn)
• Institut Universitaire du Cancer Toulouse - Oncopole — Toulouse, France (Recruiting)
• Gustave Roussy — Villejuif Cedex, France (Recruiting)
• Institut Català d'Oncologia-Hospital Duran i Reynals — Barcelona, Spain (Recruiting)
• Hospital Universitario 12 de Octubre — Madrid, Spain (Recruiting)
• Hospital Universitari i Politècnic La Fe — Valencia, Spain (Recruiting)

Study contacts

• Study coordinator: Affimed GmbH

Conditions Acute Myeloid Leukemia