Acute Myeloid LeukemiaPhase 1NCT05817058
First-in-Human Dose Escalation Study of AFM28 in Patients With Relapsed/Refractory Acute Myeloid Leukemia
A Phase 1 study testing AFM28 in people with Acute Myeloid Leukemia, run by Affimed GmbH at 5 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- AFM28
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 21 Mar 2023to 13 Jun 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
Spain3 sites
Institut Català d'Oncologia-Hospital Duran i Reynals
Barcelona, 08907
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitari i Politècnic La Fe
Valencia, CP 46026
France2 sites
Institut Universitaire du Cancer Toulouse - Oncopole
Toulouse, 31059
Gustave Roussy
Villejuif, 94805
About this study
Official title: 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 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.
Read the detailed description
The study drug will be given by intravenous infusion once weekly as long as the subject is deriving clinical benefit until disease progression or other treatment discontinuation criteria met, unacceptable toxicity, or subject's refusal, whichever occurs first. The dose-limiting toxicity observation period will be 28 days, reflecting adequate exposure for safety assessment. The dose-escalation scheme will follow a Bayesian logistic regression model. A safety review committee will monitor safety and recommend all cohort dosing decisions. The starting First In Human dose for AFM28 will be 25 mg i.v. and treatment in each cohort will utilize a staggered approach, with at least 7 days between the first dose of the first subject and the first dose of subsequent subjects. In order to gather additional Pharmacokinetics/ Pharmacodynamics and safety data to inform potential final dose escalation decisions and selection of one or more recommended phase 2 doses at selected dose levels, additional subjects may be enrolled in at least two cohorts consistent with backfilling a cohort (up to 12 subjects).
- Conditions
- Acute Myeloid Leukemia
- Being tested
- AFM28
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AFM28Drug
AFM28 dose escalation
| Study group | Role | What they receive |
|---|---|---|
| Treatment of escalating doses of AFM28 | Experimental | AFM28 first in human starting dose will be 25 mg i.v. Receives: Drug: AFM28 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 28 days following the first dose of study treatment
Secondary outcomes (14)
Incidence and severity of Treatment Emergent Adverse Events
Incidence and severity of Treatment Emergent Adverse Events
Measured: through study completion (up to 36 weeks)
Incidence and severity of Serious Adverse Events
Incidence and severity of Serious Adverse Events
Measured: through study completion (up to 36 weeks)
Incidence of subjects developing anti-drug antibodies
Incidence of anti-drug antibodies during treatment with AFM28 (by measurement of anti-drug antibodies before and throughout treatment with AFM28)
Measured: through study completion (up to 36 weeks)
Area under the concentration-time curve
Area under the concentration-time curve over the dose interval
Measured: cycle 1 (day 1 and day 28)
Cmax
Maximum observed plasma concentration
Measured: cycle 1 (day 1 and day 28)
Tmax
Time to reach maximum observed plasma concentration
Measured: cycle 1 (day 1 and day 28)
Ctrough
Concentration measured immediately prior to the fourth dose
Measured: immediately prior to the fourth dose
Complete Response
Complete response (Disease assessment in accordance with the International Working Group (IWG) criteria for AML and the European Leukemia Network (ELN) 2017 classification criteria)
Measured: Through treatment period until 14 days after last dose
Complete Response hematological
Complete Response with partial hematologic recovery (Disease assessment in accordance with the IWG criteria for AML and the ELN 2017 classification criteria)
Measured: Through treatment period until 14 days after last dose
Complete Response composite rate
Composite complete response rate (Disease assessment in accordance with the IWG criteria for AML and the ELN 2017 classification criteria)
Measured: Through treatment period until 14 days after last dose
Complete Response + Complete Response hematological rate
Complete Response plus Complete Response with partial hematologic recovery rate (Disease assessment in accordance with the IWG criteria for AML and the ELN 2017 classification criteria)
Measured: Through treatment period until 14 days after last dose
Overall Response Rate
Overall response rate (Disease assessment in accordance with the IWG criteria for AML and the ELN 2017 classification criteria)
Measured: Through treatment period until 14 days after last dose
Disease Control Rate
Disease control rate (Disease assessment in accordance with the IWG criteria for AML and the ELN 2017 classification criteria)
Measured: Through treatment period until 14 days after last dose
Duration of Response
Duration of Response (Disease assessment in accordance with the IWG criteria for AML and the ELN 2017 classification criteria)
Measured: Through treatment period until 14 days after last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2023
- Study start21 Mar 2023
- Primary completion28 Nov 2024
- Study completion13 Jun 2025
Why it stopped: As decided by sponsor
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Affimed GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lydia Wunderle, Study director, Affimed GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05817058
- Sponsor's protocol ID
- AFM28-101
- Status last verified
- Jul 2025
- First submitted
- 22 Mar 2023
- Last updated
- 23 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05817058
- Acronym / sponsor ID
- AFM28-101
- Conditions
- Acute Myeloid Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: As decided by sponsor
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Affimed GmbHIndustry (pharma, biotech, devices)
- Study start
- 21 Mar 2023 (actual)
- Primary completion
- 28 Nov 2024 (actual)
- Study completion
- 13 Jun 2025 (actual)
- First posted
- 18 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The study drug will be given by intravenous infusion once weekly as long as the subject is deriving clinical benefit until disease progression or other treatment discontinuation criteria met, unacceptable toxicity, or subject's refusal, whichever occurs first. The dose-limiting toxicity observation period will be 28 days, reflecting adequate exposure for safety assessment. The dose-escalation scheme will follow a Bayesian logistic regression model. A safety review committee will monitor safety and recommend all cohort dosing decisions. The starting First In Human dose for AFM28 will be 25 mg i.v. and treatment in each cohort will utilize a staggered approach, with at least 7 days between the first dose of the first subject and the first dose of subsequent subjects. In order to gather additional Pharmacokinetics/ Pharmacodynamics and safety data to inform potential final dose escalation decisions and selection of one or more recommended phase 2 doses at selected dose levels, additional subjects may be enrolled in at least two cohorts consistent with backfilling a cohort (up to 12 subjects).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment of escalating doses of AFM28 | Experimental | Drug: AFM28AFM28 first in human starting dose will be 25 mg i.v. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AFM28AFM28 dose escalation | Drug | Treatment of escalating doses of AFM28 |
Primary outcome
The Incidence of dose limiting toxicities
Time frame: 28 days following the first dose of study treatment
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
14 secondary outcomes
Incidence and severity of Treatment Emergent Adverse Events
Time frame: through study completion (up to 36 weeks)
Incidence and severity of Serious Adverse Events
Time frame: through study completion (up to 36 weeks)
Incidence of subjects developing anti-drug antibodies
Time frame: through study completion (up to 36 weeks)
Area under the concentration-time curve
Time frame: cycle 1 (day 1 and day 28)
Cmax
Time frame: cycle 1 (day 1 and day 28)
Tmax
Time frame: cycle 1 (day 1 and day 28)
Ctrough
Time frame: immediately prior to the fourth dose
Complete Response
Time frame: Through treatment period until 14 days after last dose
Complete Response hematological
Time frame: Through treatment period until 14 days after last dose
Complete Response composite rate
Time frame: Through treatment period until 14 days after last dose
Complete Response + Complete Response hematological rate
Time frame: Through treatment period until 14 days after last dose
Overall Response Rate
Time frame: Through treatment period until 14 days after last dose
Disease Control Rate
Time frame: Through treatment period until 14 days after last dose
Duration of Response
Time frame: Through treatment period until 14 days after last dose
Results and safety
The study was stopped early (reason given: As decided by sponsor). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lydia Wunderle study director
Affimed GmbH
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AFM28 in people with Acute Myeloid Leukemia, run by Affimed GmbH at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Spain, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: As decided by sponsor). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Incidence of dose limiting toxicities (time frame: 28 days following the first dose of study treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2025.