SEA-CD70 for Myelodysplastic Syndrome and Acute Myeloid Leukemia

Recruiting at 70 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Seagen, a wholly owned subsidiary of Pfizer

Must not be taking: CYP3A inducers

Disqualifiers: Stem cell transplant, CNS leukemia, others

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

Compensation: Varies

Number of Visits: Unknown

178 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, SEA-CD70, to determine its safety and effectiveness in treating two blood-related conditions: myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Researchers are also evaluating SEA-CD70 in combination with other drugs, such as azacitidine and venetoclax, to identify optimal doses and assess their combined efficacy. The trial consists of seven parts, each focusing on different combinations and stages of these diseases. Individuals with MDS or AML that have not responded to previous treatments and have no other options might be suitable candidates for this trial. As a Phase 1 trial, the research aims to understand how the treatment works in people, and participants will be among the first to receive this new drug.

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, for Part G, you cannot use strong or moderate CYP3A inducers (a type of drug that affects how your body processes other medications). It's best to discuss your current medications with the trial team.

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

Research has shown that SEA-CD70, whether used alone or with azacitidine, is generally well tolerated. In earlier studies, patients who took SEA-CD70 at doses of 10 mg/kg and 20 mg/kg experienced manageable side effects. Importantly, these studies did not find any severe side effects related to the treatment.

When combined with azacitidine, SEA-CD70 has shown safety, with no major safety concerns reported at these doses. This suggests the combination is generally safe. However, these findings come from early studies, which usually focus on safety and dosage. As the treatment undergoes further research, more detailed safety information will become available.

For the combination of SEA-CD70, azacitidine, and venetoclax, specific safety data is not yet detailed in available sources. This phase of the trial mainly aims to understand safety and determine the right dosage for these drugs together. Therefore, the safety of this combination is still under close study, and findings are expected to evolve as research continues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) target cancer cells broadly. But SEA-CD70 works differently, targeting the CD70 protein found on the surface of certain cancer cells. This targeted approach aims to attack cancer cells more precisely, potentially reducing harm to healthy cells. Researchers are excited because SEA-CD70 is combined with azacitidine and venetoclax in some trial arms, which may enhance its effectiveness, especially in patients who are previously untreated or unfit for standard induction therapy. This combination could offer new hope for those who have not responded well to existing therapies.

What evidence suggests that this trial's treatments could be effective for MDS and AML?

Research has shown that SEA-CD70 targets a specific pathway that aids leukemia cell growth. By blocking this pathway, SEA-CD70 aims to slow cancer progression. This trial studies SEA-CD70 across various treatment arms. Early results suggest that SEA-CD70, used alone or with azacitidine, shows promise, particularly for patients with high-risk myelodysplastic syndrome (HR-MDS). Azacitidine boosts the immune system's ability to fight cancer cells. In one arm of this trial, SEA-CD70 is combined with azacitidine and venetoclax, which has proven effective in treating similar conditions. Although more research is needed, these early findings offer hope for treating MDS and AML. ^{1 2 3 4 6}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Participants must have relapsed after partial remission or shown no response to previous treatments like azacitidine. They should be in good physical condition, with an ECOG performance status of 0-1, and not have other treatment options available.

Inclusion Criteria

I had a severe reaction to HMA treatment and had to stop it.

My MDS has returned or is not responding to treatment, and I have no other known beneficial treatment options.

You have an abnormal percentage of immature blood cells in either your bone marrow or peripheral blood.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part A: Dose escalation to identify the maximum tolerated dose (MTD) or recommended expansion dose of SEA-CD70 monotherapy in participants with relapsed/refractory MDS

Up to 4 weeks

Dose Expansion

Parts B and C: Evaluate safety and tolerability of SEA-CD70 monotherapy in participants with relapsed/refractory MDS and AML

Up to 2 years

Combination Dose Finding

Part D: Dose-finding and optimization of SEA-CD70 with azacitidine in participants with MDS or MDS/AML

Up to 4 weeks

Combination Dose Expansion

Parts E and F: Evaluate safety and tolerability of SEA-CD70 with azacitidine in participants with MDS or MDS/AML

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• SEA-CD70

Trial Overview

The study tests SEA-CD70 alone and combined with azacitidine to determine the safe dosage levels and effectiveness against MDS and AML. It's divided into six parts, each aiming to establish safety profiles and dosages for different patient groups within these conditions.

How Is the Trial Designed?

Group I: Part G Experimental Treatment 3 Interventions

SEA-CD70 + azacitidine +venetoclax dose-finding/dose optimization in previously untreated and unfit for induction therapy AML

Group II: Part F Experimental Treatment 2 Interventions

SEA-CD70 + azacitidine expansion cohort in relapsed/refractory MDS or MDS/AML

Group III: Part E Experimental Treatment 2 Interventions

SEA-CD70 + azacitidine expansion cohort in previously untreated higher-risk MDS or MDS/AML

Group IV: Part D Experimental Treatment 2 Interventions

SEA-CD70 + azacitidine dose-finding/dose optimization cohorts in relapsed/refractory MDS or MDS/AML, and previously untreated higher-risk MDS or MDS/AML

Group V: Part C Experimental Treatment 1 Intervention

SEA-CD70 expansion cohort in relapsed/refractory AML

Group VI: Part B Experimental Treatment 1 Intervention

SEA-CD70 expansion cohort in relapsed/refractory (HMA-failure) MDS

Group VII: Part A Experimental Treatment 1 Intervention

SEA-CD70 dose escalation cohort in relapsed/refractory (HMA-failure) MDS

Who Is Running the Clinical Trial?

Seagen, a wholly owned subsidiary of Pfizer

Lead Sponsor

Trials

20

Recruited

4,900+

Seagen Inc.

Lead Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Published Research Related to This Trial

Priming with GM-CSF and ATRA during induction chemotherapy for acute myeloid leukemia (AML) resulted in a higher complete remission rate of 61.5% compared to 41.4% in a historical control group, suggesting enhanced efficacy of this treatment approach.

While the combination treatment showed promising response rates, it also presented significant side effects, including fever and skin lesions, indicating that while effective, the regimen carries notable toxicity risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of priming with granulocyte macrophage colony-stimulating factor plus all-trans retinoic acid combined with remission induction chemotherapy in patients with acute myeloid leukemia. Shin, HJ., Chung, JS., Choi, YJ., et al.[2013]

Acute Myeloid Leukemia (AML) remains a challenging disease with limited treatment advancements over the years, emphasizing the urgent need for new therapeutic strategies.

Recent research has identified promising new targets and therapies, including those that focus on key signaling pathways and drug resistance mechanisms in AML, which could lead to improved treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Signal transduction in Acute Myeloid Leukemia - Implications for Novel Therapeutic Concepts. Konig, H., Santos, CD.[2019]

CD72 has been identified as a novel tumor-associated antigen (TAA) that is highly expressed in pediatric acute leukemias, particularly in B-cell precursor acute lymphoblastic leukemias (BCP-ALL) and most acute myeloid leukemias (AML), based on analysis of 495 pediatric bone marrow samples.

The expression of CD72 in BCP-ALL cases, even those with CD19 loss, suggests its potential as a reliable target for advanced diagnostics and immunotherapy, making it a promising candidate for treating various forms of acute leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD72 is a pan-tumor antigen associated to pediatric acute leukemia. Buldini, B., Faggin, G., Porcù, E., et al.[2023]

In a study of 24 acute myelogenous leukemia (AML) patients treated with all-trans retinoic acid, theophylline, and valproic acid, 9 out of 22 evaluable patients showed increased normal blood cell counts, indicating a positive response to the therapy.

Patients who responded to the treatment had a significantly longer median survival of 147 days compared to 48 days for non-responders, suggesting that this combination therapy may stabilize the disease in a subset of AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A subset of patients with high-risk acute myelogenous leukemia shows improved peripheral blood cell counts when treated with the combination of valproic acid, theophylline and all-trans retinoic acid. Ryningen, A., Stapnes, C., Lassalle, P., et al.[2013]

In a study of 96 adult patients with acute myelocytic leukaemia (AML), the expression of CD34 and HLA-DR antigens was found to significantly predict response to intensive chemotherapy, with CD34-positive patients showing a lower complete remission rate (59%) compared to CD34-negative patients (87%).

Patients with CD34-positive AML are less likely to achieve complete remission and may require alternative treatment strategies, as they tend to have a higher incidence of secondary AML and chromosomal abnormalities, and relapses consistently present with CD34-positive disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic importance of immunophenotyping in adults with acute myelocytic leukaemia: the significance of the stem-cell glycoprotein CD34 (My10) Geller, RB., Zahurak, M., Hurwitz, CA., et al.[2019]

In a study of 168 adults with acute myeloid leukemia (AML), myeloid markers CD13 and CD33 were found to be the most effective for diagnosing AML, with 71% and 79% positivity, respectively.

The presence of certain antigens, particularly CD11b and CD9, was associated with poorer treatment responses and shorter survival, indicating their potential prognostic value in AML management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic value of immunophenotyping in acute myeloid leukemia. Australian Leukaemia Study Group. Bradstock, K., Matthews, J., Benson, E., et al.[2021]

The CD70/CD27 signaling pathway is active in acute myeloid leukemia (AML) cells, promoting their proliferation and self-renewal, which contributes to poor patient outcomes.

Blocking the CD70/CD27 interaction with monoclonal antibodies led to differentiation and reduced growth of AML cells in laboratory models, while sparing healthy stem/progenitor cells, suggesting a targeted therapeutic approach for AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD70/CD27 signaling promotes blast stemness and is a viable therapeutic target in acute myeloid leukemia. Riether, C., Schürch, CM., Bührer, ED., et al.[2021]

Current chemotherapy for acute myeloid leukemia (AML) may have reached its limits, prompting a shift towards more targeted therapies that consider the disease's molecular and biological characteristics.

Targeting the CD33 antigen with antibody-directed treatments has shown promise, especially in relapsed cases, but is unlikely to replace conventional chemotherapy; ongoing trials are exploring the effectiveness of combining these targeted therapies with traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting treatment in AML. Burnett, AK., Knapper, S.[2016]

Citations

1.

ashpublications.org

ashpublications.org/blood/article/144/Supplement%201/1840/530030/PF-08046040-SEA-CD70-a-Nonfucosylated-CD70

PF-08046040 (SEA-CD70), a Nonfucosylated CD70-Directed ...

Overall, AEs were manageable, and there were no treatment-related or treatment-emergent dose reductions. Preliminary efficacy was observed for ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04227847

NCT04227847 | A Safety Study of SEA-CD70 in Patients ...

This trial will look at a drug called SEA-CD70 with and without azacitidine, to find out if it is safe for participants with myelodysplastic syndrome (MDS) ...

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0006497124045877

PF-08046040 (SEA-CD70), a Nonfucosylated ...

Overall, AEs were manageable, and there were no treatment-related or treatment-emergent dose reductions. Preliminary efficacy was observed for pts with HR-MDS, ...

4.

trialx.com

trialx.com/clinical-trials/listings/255366/a-safety-study-of-sea-cd70-in-patients-with-myeloid-malignancies/

A Safety Study of SEA-CD70 in Patients With Myeloid ...

This trial will look at a drug called SEA-CD70 with and without azacitidine, to find out if it is safe for patients with myelodysplastic ...

5.

withpower.com

withpower.com/trial/phase-1-7-2020-b7695

SEA-CD70 for Myelodysplastic Syndrome and Acute ...

SEA-CD70 is unique because it targets the CD70/CD27 signaling pathway, which is involved in the growth and survival of leukemia cells. By blocking this pathway, ...

6.

ctv.veeva.com

ctv.veeva.com/study/a-safety-study-of-sea-cd70-in-patients-with-myeloid-malignancies

A Safety Study of SEA-CD70 in Patients With Myeloid ...

This trial will look at a drug called SEA-CD70 with and without azacitidine, to find out if it is safe for participants with myelodysplastic ...