APVO436 + Venetoclax + Azacitidine for AML

Recruiting at 7 trial locations

Overseen By Caroline Taromino

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Aptevo Therapeutics

Must be taking: Venetoclax, Azacitidine

Must not be taking: Hypomethylating agents, Chemotherapy

Disqualifiers: Autoimmune disorders, CNS involvement, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 28-day cycles

39 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments for individuals with acute myeloid leukemia (AML) that is untreated and tests positive for CD123 markers. Researchers are combining APVO436 (an experimental treatment) with venetoclax and azacitidine to determine the optimal dose levels. This approach aims to assist those unable to undergo standard intensive treatments due to health conditions like heart or lung issues. For those recently diagnosed with AML who have not started treatment, this trial might be suitable. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on certain treatments for AML or related conditions, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of APVO436, venetoclax, and azacitidine is safe and promising. Studies have found that this combination leads to positive results in patients with acute myeloid leukemia (AML), helping to prevent cancer recurrence for a significant time.

APVO436 alone is well-tolerated, meaning most people can take it without serious side effects. It is important to note that this combination is still undergoing early trials to determine the best dose. While information on long-term safety is limited, it appears to be well-tolerated so far. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for AML?

Researchers are excited about the combination of APVO436 with Venetoclax and Azacitidine for treating acute myeloid leukemia (AML) because it offers a novel approach by targeting CD123, a protein commonly found on AML cells. Unlike standard treatments like chemotherapy, which kill both healthy and cancerous cells, APVO436 is designed to specifically attack cancer cells, potentially leading to fewer side effects. Additionally, Venetoclax and Azacitidine are already known to be effective in treating AML, and the combination with APVO436 could enhance their effectiveness, offering new hope for patients with newly diagnosed, CD123+ AML.

What evidence suggests that this treatment might be an effective treatment for AML?

Research has shown that combining APVO436 with venetoclax and azacitidine yields promising results for treating acute myeloid leukemia (AML). In one study, all patients benefited from the treatment, positively affecting their condition. Another study found that this combination led to long-lasting remissions, with cancer symptoms greatly reduced or disappearing over time. Additionally, when venetoclax and azacitidine were used together, more than half of the patients, especially those newly diagnosed, went into remission. These findings suggest that this treatment combination, which participants in this trial will receive, could be effective for patients with AML. ^{1 4 6 7 8}

Who Is on the Research Team?

Dirk Huebner, MD

Principal Investigator

Aptevo Therapeutics

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly diagnosed, CD123+ Acute Myeloid Leukemia (AML) who haven't been treated before. They should be able to perform daily activities with some limitations (ECOG status 2 or 3), have a life expectancy of at least 12 weeks, and their major organs must function within certain limits.

Inclusion Criteria

6. Hepatic disorder with total bilirubin between 1.5 and 3 times the ULN 5. Patient must have a projected life expectancy of ≥12 weeks

I am 18 or older with confirmed AML and have not received treatment for it.

I have limited self-care abilities and spend more than half of my waking hours in bed or a chair.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive APVO436 in combination with venetoclax and azacitidine in 28-day cycles, with dose escalation across five cohorts

28-day cycles

Multiple visits per cycle for IV infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of complete remission rate

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• APVO436

Trial Overview The study tests different doses of APVO436 combined with venetoclax and azacitidine in patients. It's an open-label trial, meaning everyone knows what treatment they're getting, and it aims to find the best dose level for this combination therapy.

How Is the Trial Designed?

Group I: Treatment Arm APVO436 in combination with Venetoclax and Azacitidine Experimental Treatment 3 Interventions

APVO436 at escalating dose levels in combination with venetoclax and azacitidine (ven/aza) in adult patients with newly diagnosed, CD123+ AML.

Who Is Running the Clinical Trial?

Aptevo Therapeutics

Lead Sponsor

Trials

9

Recruited

490+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06634394

NCT06634394 | APVO436 Phase 1b/2 Study in Patients ... A multi-center, open-label, dose-finding study of five dose levels of APVO436 in combination with venetoclax and azacitidine (ven/aza) in adult ...

2. aptevotherapeutics.gcs-web.com aptevotherapeutics.gcs-web.com/news-releases/news-release-details/100-clinical-benefit-rate-achieved-phase-1b-trial-evaluating

100% Clinical Benefit Rate Achieved in Phase 1b Trial ... 100% Clinical Benefit Rate Achieved in Phase 1b Trial Evaluating APVO436 in Combination with Venetoclax and Azacitidine for Venetoclax Treatment ...

3. onclive.com onclive.com/view/apvo436-plus-venetoclax-azacitidine-produces-durable-remissions-in-relapsed-refractory-aml

APVO436 Plus Venetoclax/Azacitidine Produces Durable ... Treatment with the CD3 x CD123 bispecific antibody APVO436 plus venetoclax and azacitidine led to durable remissions in patients with relapsed/ ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40951718/

Real-world outcomes of azacitidine plus venetoclax in ... After treatment, more than half went into remission (the cancer was no longer detectable), and those with newly diagnosed AML had better ...

5. cancernetwork.com cancernetwork.com/view/mipletamig-soc-achieved-complete-remission-rates-in-front-line-aml

Mipletamig/SOC Achieved Complete Remission Rates in ... Results from the RAINIER trial showed that mipletamig, venetoclax, and azacitidine achieved a complete remission rate of 90% in patients with AML.

6. cancernetwork.com cancernetwork.com/view/apvo436-combo-yields-favorable-responses-in-acute-myeloid-leukemia

APVO436 Combo Yields Favorable Responses in Acute ... APVO436 yielded positive clinical outcomes in combination with venetoclax (Venclexta) and azacitidine among patients with acute myeloid leukemia (AML) or ...

7. aptevotherapeutics.gcs-web.com aptevotherapeutics.gcs-web.com/news-releases/news-release-details/phase-1b2-rainier-frontline-acute-myeloid-leukemia-aml-trial

Phase 1b/2 "RAINIER" Frontline Acute Myeloid Leukemia ... This trial aims to identify the recommended Phase 2 dose and further evaluate key indicators-such as safety, tolerability, and efficacy-of mipletamig.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8793782/

PMC - PubMed Central APVO436 showed promising tolerability and single-agent activity in relapsed or refractory (R/R) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).