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NCT Number: NCT04227847

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

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) and acute myeloid leukemia (AML). It will study SEA-CD70 to find out what its side effects are and if it works for AML and MDS. A side effect is anything the drug does besides treating cancer.

This study will have seven groups or "parts."

* Part A will find out how much SEA-CD70 should be given to participants * Part B will use the dose found in Part A to find out how safe SEA-CD70 is and if it works to treat participants with MDS. * Part C will use the dose found in Part A to find out how safe SEA-CD70 is and if it works to treat participants with AML. * Part D will find out how much SEA-CD70 with azacitidine should be given to participants * Part E will use the dose found in Part D to find out how safe SEA-CD70 with azacitidine is and if it works to treat participants with MDS or MDS/AML that has not been treated. * Part F will use the dose found in Part D to find out how safe SEA-CD70 with azacitidine is and if it works to treat participants with MDS or MDS/AML. * Part G will find out how much SEA-CD70 with azacitidine and with venetoclax should be given to participants with AML. Also, to evaluate safety and tolerability of PF-08046040 in combination with azacitidine and venetoclax in participants with previously untreated AML who are unfit for standard induction chemotherapy.

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Key information

Conditions

Myelodysplastic Syndrome Acute Myeloid Leukemia Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Myelodysplastic Syndromes Neoplasms Neoplasms by Histologic Type

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

National Cancer Center Hospital East, Kashiwa, Chiba, Japan

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About this study

This is a phase 1, open-label, multicenter, dose-finding, and dose expansion study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of SEA-CD70 monotherapy and SEA-CD70 in combination with azacitidine in adults with myeloid malignancies. The study will be conducted in up to 6 parts.

  • Part A is a dose-escalation cohort designed to identify the MTD or recommended expansion dose of SEA-CD70 monotherapy in participants with relapsed/refractory (hypomethylating agent [HMA]-failure) MDS.
  • Part B is an expansion cohort designed to evaluate the safety and tolerability of SEA-CD70 monotherapy in participants with relapsed/refractory (HMA-failure) MDS.
  • Part C is an expansion cohort designed to evaluate the safety and tolerability of SEA-CD70 monotherapy in participants with relapsed/refractory AML.
  • Part D contains dose-finding/dose optimization cohorts designed to evaluate the safety/tolerability and identify the recommended expansion dose of SEA-CD70 in combination with azacitidine in participants with 1) relapsed/refractory (HMA-failure) MDS or MDS/AML, and 2) previously untreated higher-risk per IPSS-M (Moderate High, High or Very High) MDS or MDS/AML.
  • Part E is an expansion cohort designed to evaluate the safety and tolerability of SEA-CD70 in combination with azacitidine in participants with previously untreated higher-risk per IPSS-M (Moderate High, High, or Very High) MDS or MDS/AML.
  • Part F is an expansion cohort designed to evaluate the safety and tolerability of SEA-CD70 in combination with azacitidine in participants with relapsed/refractory (HMA-failure) MDS or MDS/AML.
  • Part G will find out how much SEA-CD70 with azacitidine and with venetoclax should be given to participants with previously untreated AML who are unfit for standard of care induction chemotherapy

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Part A Inclusion Criteria

  • Participants with cytologically/histologically confirmed MDS (2016 World Health Organization (WHO) classification) with
  • Measurable disease per WHO MDS with excess blasts criteria
  • MDS that is relapsed or refractory and must not have other therapeutic options
  • Treatment failure after prior hypomethylating agent (HMA) therapy for MDS
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

Part B Inclusion Criteria

  • Participants with cytologically/histologically confirmed MDS (WHO classification) with:
  • Measurable disease per WHO MDS with excess blasts (MDS-EB) criteria
  • MDS that is relapsed or refractory and must not have other therapeutic options
  • Treatment failure after prior HMA therapy for MDS
  • ECOG Performance Status of 0-2

Part C Inclusion Criteria

  • Participants with relapsed or refractory AML (ICC 2022) (except for acute promyelocytic leukemia [APL]):
  • Who have received either 2 or 3 previous regimens
  • Who have received 1 previous regimen to treat active disease and have at least one of the following:
  • Age > 60 and ≤75 years.
  • Primary resistant AML or secondary AML
  • First CR duration <6 months
  • Adverse-risk per European Leukemia Network genetic risk stratification
  • Age 18-75 years
  • ECOG performance status of 0-2

Parts D and F Inclusion Criteria

  • Participants with diagnosis of MDS or MDS/AML (ICC 2022 criteria)
  • Disease which has relapsed, failed to respond after minimum of 6 cycles, or progressed following an HMA in the immediately preceding line of therapy.
  • Eligible for continued therapy with azacitidine
  • ECOG Performance Status 0-2

Parts D and E Inclusion Criteria

  • Participants with diagnosis of MDS or MDS/AML (ICC 2022 criteria), previously untreated.
  • Participants with higher-risk per IPSS-M MDS and MDS/AML
  • ECOG Performance Status 0-2

Part G Inclusion Criteria

  • Participants with diagnosis of AML (ICC 2022 criteria), previously untreated and ineligible for standard induction chemotherapy.
  • Age ≥18 years.
  • ECOG Performance Status of 0-2.

Exclusion criteria

(All Parts)

  • Previous exposure to CD70-targeted agents
  • Prior allogeneic hematopoietic stem cell transplant, for any condition
  • Central nervous system leukemia
  • History of clinically significant sickle cell anemia, autoimmune hemolytic anemia, or idiopathic thrombocytopenic purpura
  • Parts D, F and G only: Prior oral HMA or oral HMA-combinations
  • Part G: conditions that preclude enteral route of administration; concomitant use of strong/moderate CYP3A inducers; history of myeloproliferative neoplasm

Treatment and study plan

SEA-CD70

Drug

Given into the vein (IV; intravenously) on Days 1 and 15 of each treatment cycle

Azacitidine

Drug

75mg/m^2 injected under the skin (SC; subcutaneous) or given into the vein (IV; intravenously) on Days 1 through 7 of each treatment cycle.

Other names: VIDAZA

Venetoclax

Drug

400 mg /day PO, continuously; administered with ramping

Other names: Venclexta

Primary outcomes

  1. Number of participants with adverse events (AEs)

    Time frame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years

    Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.

  2. Number of participants with laboratory abnormalities

    Time frame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years

    To be summarized using descriptive statistics.

  3. Number of participants with a dose-limiting toxicity (DLT) at each dose level (Parts A and D only)

    Time frame: Though end of DLT evaluation period; up to approximately 4 weeks

    To be summarized using descriptive statistics.

Secondary outcomes

  1. AUC - Area under the plasma concentration-time curve

    Time frame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years

    To be summarized using descriptive statistics.

  2. Tmax - Time to maximum concentration attained

    Time frame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years

    To be summarized using descriptive statistics.

  3. Cmax - Maximum observed plasma concentration

    Time frame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years

    To be summarized using descriptive statistics.

  4. Ctrough - Minimum plasma concentration per dosing interval

    Time frame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years

    To be summarized using descriptive statistics.

  5. T1/2 - Terminal elimination half-life

    Time frame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years

    To be summarized using descriptive statistics.

  6. Incidence of antidrug antibodies (ADA)

    Time frame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years

    To be summarized using descriptive statistics.

  7. Complete remission (CR) Rate and complete remission equivalent (CReq) rate

    Time frame: Up to approximately 4 years

    Proportion of participants with AML, MDS/AML or MDS who achieve CR or CReq

  8. Complete remission with incomplete blood count recovery (CRi) rate

    Time frame: Up to approximately 4 years

    Proportion of participants with AML who achieve CRi

  9. Complete remission with limited count recovery (CRL) rate for participants with MDS or MDS/AML

    Time frame: Up to approximately 4 years

    Proportion of participants with MDS or MDS/AML who achieve CRL

  10. Complete remission with partial hematologic recovery (CRh) rate

    Time frame: Up to approximately 4 years

    Proportion of participants with AML, MDS/AML, or MDS who achieve CRh

  11. Hematologic response (HI) rate

    Time frame: Up to approximately 4 years

    Proportion of participants with MDS or MDS/AML with HI

  12. Overall response rate (ORR)

    Time frame: Up to approximately 4 years

    For AML, the proportion of participants who achieve a best response of CR, CRi, CRh, or partial response (PR). For MDS, the proportion of participants who achieve a best response of CR, CReq, CRL, CRh, PR, or HI

  13. Duration of remission (DOR)

    Time frame: Up to approximately 4 years

    For AML, the time from first CR/CRi/CRh/PR response to the first documentation of disease progression, start of new anticancer therapy, or death due to any cause. For MDS, the time from first CR (or Req)/CRL/CRh/PR to the first documentation of disease progression, start of new anticancer therapy, or death due to any cause

  14. Overall survival (OS)

    Time frame: Up to approximately 4 years

    Time from start of study treatment to the date of death due to any cause

  15. Event-free survival (EFS)

    Time frame: Up to approximately 4 years

    Time from first dose to the first documentation of progression, failure to achieve remission within 6 months of study entry, disease relapse, or death due to any cause, whichever comes first.

  16. Progression-free survival (PFS)

    Time frame: Up to approximately 4 years

    Time from first dose to the first documentation of progression, disease relapse, or death from any cause, whichever comes first

  17. MRD-negative ORR

    Time frame: Up to approximately 4 years

    Proportion of participants with AML or MDS who achieve MRD-negative ORR

  18. Time to response (TTR)

    Time frame: Up to approximately 4 years

    Time from start of study treatment to the first documentation of objective response

  19. Rate of conversion to transfusion independence (TI)

    Time frame: Up to approximately 4 years

    Proportion of participants who convert from transfusion dependence at baseline to TI post-baseline

  20. Rate of TI maintenance

    Time frame: Up to approximately 4 years

    Proportion of participants who were TI at baseline and maintain TI post-baseline

Study contacts

Contact information is provided by the study sponsor or research team.

Pfizer CT.gov Call Center

CONTACT

[email protected]

1-800-718-1021

Sponsors and collaborators

Lead sponsor

Seagen, a wholly owned subsidiary of Pfizer

Industry

Registry information

Official study title

A Phase 1 Study of SEA-CD70 in Myeloid Malignancies

Important dates

Study start
2020
Primary completion
2027
Study completion
2028
First posted
Jan 14, 2020
Registry last updated
Jul 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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