Phase 1 trial with AFM28 for patients with relapsed/refractory AML
Research type
Research Study
Full 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 Relapsed/Refractory Acute Myeloid Leukemia
IRAS ID
1006906
Contact name
Sandra Schmid
Contact email
Sponsor organisation
Affimed GmbH
Eudract number
2022-002702-24
Clinicaltrials.gov Identifier
Research summary
Summary of Research
Affimed GmbH is running a first-in-human Phase 1, open-label, non-randomised multiple ascending dose escalation study evaluating AFM28 as a monotherapy in participants with refractory or relapsed (R/R) CD123-positive acute myeloid leukaemia (AML) whose disease has progressed on or relapsed after treatment with previous anticancer therapies. AML is the most common acute leukaemia in adults, and is associated with a poor prognosis; only 10-15% elderly patients survive for >1 year from diagnoses. There is currently no standard-of-care AML treatment, due to poor tolerance of intensive therapies; there is an unmet need for effective R/R AML treatments. A protein called CD123 has been identified as a promising target for new therapies, due to it being highly expressed in leukaemic cancer cells, and its presence on healthy cells being limited. AFM28 is an antibody that specifically binds to the CD123 protein in leukaemic cells and activates signalling that causes cell death. AFM28 therefore aims to deplete the number of AML cancer cells. 50 participants diagnosed with CD123-positive AML are planned to take part in the study. Eligible participants will be assigned into groups, each of which will be given a varying intravenous dose of AFM28. The groups enrolled earlier in the study will receive lower doses of AFM28. If this low dose is found to be safe within the first 4 weeks of treatment, the next group of participants can receive the higher dose, and so on; this is a dose escalation study. The participants will receive AFM28 in treatment cycles, each of which will last 28 days. The number of cycles for each participant will differ, depending on if they are clinically benefitting from AFM28. Treatment will involve a minimum of 10 study visits, and will last a minimum of 9 weeks. Study assessments will include: vital signs, blood tests, ECGs, physical/neurological examination and bone marrow aspirates/biopsy.
Affimed GmbH is the sponsor and will organise/fund this study.Summary of Results
What were the results of this trial?
This is a summary of the main results from this trial. The individual results of each participant might be different and are not in this summary. The websites listed at the end of this summary may have more information about the results of this trial.
The results from several trials are needed to decide which treatments work best and are safest.
Other trials may provide new information or different results.Did the number of leukemia cells in participants' bone marrow go down or completely go away during the treatment with AFM28?
Yes. Overall, the researchers found that for some participants’ number of leukemia cells became less or completely disappeared during the treatment with AFM28.
To answer this question, the doctors measured the participants’ leukemia cells throughout the treatment period. Then, they recorded the number of participants whose leukemia cells became less
or completely disappeared. Overall, the researchers found that at the end of treatment:
In 16,7% of the participants the leukemia cells became less or completely disappeared. This was 5
out of 30 participants.What medical problems happened during this trial?
Summary of adverse reactions
This section is a summary of the medical problems that the participants had during the trial that
the trial doctors thought could possibly be related to the trial treatment. These medical problems
are called “adverse reactions”. An adverse reaction can be “serious” or “non-serious”. An adverse
reaction is considered serious when it is life-threatening, causes the participant to go or stay at a
hospital, causes disability, causes a baby to be born with medical problems, or causes death.
The adverse reactions shown in this summary may or may not be related to the trial treatment.
This is because the results from several trials are needed to decide if a treatment causes an
adverse reaction. The websites listed at the end of this summary may have additional information
about any adverse reactions that happened during this trial.Did any adverse reactions happen during this trial?
There were participants who had adverse reactions during this trial. 17% (5 participants) had serious adverse events, 63% (19 participants) had adverse reactions and 13.3% (3 participants) left the trial due to adverse reactions.
What serious adverse reactions happened during this trial?
The most common serious adverse reaction related to AFM28 that happened during this trial was
a reaction or medical problem while or shortly after the intravenous infusion was given (infusion related reaction) which impacted 10% of the participants. All of these infusion related reactions were not life- threatening and didn´t cause a death.
1 participant died due to a serious adverse reactions possibly related to AFM28 during this trial, the
reason was an inflammation of the lung (pneumonitis).
1 participant experienced a headache and 1 participant had Cytokine Release Syndrome: immune reaction where the body releases too many inflammatory proteins (cytokines) into the blood
too quickly, often causing fever, low blood pressure, and organ problems.What adverse reactions happened during this trial?
The most common adverse reaction that happened during this trial was a reaction or medical
problem while or shortly after the intravenous infusion was given (infusion-related reaction) which impacted 46.7% (14) of the participants. 7% (2 participants) experienced Pyrexia (high temperature), 7% (2 participants) experienced a Headache and 7% (2 participants) experienced Cytokine release syndrome: immune reaction where the body releases too many inflammatory proteins (cytokines) into the blood too quickly, often causing fever, low blood pressure, and organ problems. There were other adverse reactions, but those happened in fewer participants.What did the researchers learn from this trial?
This trial helped researchers learn more about how well AFM28 works and how safe it is in
participants with acute myeloid leukemia.
The results from several trials are needed to decide which treatments work best and are safest.
This summary shows only the main results from this one trial. Other trials may provide new
information or different results.REC name
London - Central Research Ethics Committee
REC reference
23/LO/0155
Date of REC Opinion
21 Mar 2023
REC opinion
Further Information Favourable Opinion