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

A Phase 1 Study of SEA-CD70 in 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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndrome
• Intervention / Treatment: Drug: SEA-CD70; Drug: azacitidine; Drug: Venetoclax

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 178
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

Study Locations

• Japan
  • Yamagata, Japan, 990-9585
    • Recruiting
    • Yamagata University Hospital
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8603
      • Recruiting
      • Nippon Medical School Hospital
• Netherlands
  • Utrecht, Netherlands, 3584 CW
    • Recruiting
    • Pharmacy - UMC Utrecht t.a.v. Apotheek KGO
  • Utrecht, Netherlands, 3584 CX
    • Recruiting
    • University Medical Center (UMC) Utrecht
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Active, not recruiting
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35249
      • Active, not recruiting
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35294
      • Active, not recruiting
      • Dept. of Medicine, UAB ONeal Comprehensive Cancer Center
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope (City of Hope National Medical Center, City Of Hope Medical Center)
    • Duarte, California, United States, 91010
      • Recruiting
      • IP Address: City of Hope Investigational Drug Services(IDS)
    • Los Angeles, California, United States, 90095
      • Recruiting
      • Ronald Reagan UCLA Medical Center
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA Hematology-Oncology Clinic
  • Colorado
    • Denver, Colorado, United States, 80218
      • Active, not recruiting
      • Colorado Blood Cancer Institute
    • Denver, Colorado, United States, 80218
      • Active, not recruiting
      • Colorado Blood Cancer Institute, Lab
    • Denver, Colorado, United States, 80218
      • Active, not recruiting
      • Presbyterian/St. Luke's Medical Center
  • Kansas
    • Fairway, Kansas, United States, 66205
      • Recruiting
      • The University of Kansas Clinical Research Center
    • Fairway, Kansas, United States, 66205
      • Recruiting
      • The University of Kansas Cancer Center ,Investigational Drug Services
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • University of Kansas Medical Center Research Institute
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • The University of Kansas Hospital
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • University of Kansas Hospital Cambridge North Tower A
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • University of Kansas Medical center Medical office building
    • Overland Park, Kansas, United States, 66210
      • Recruiting
      • The University of Kansas Cancer Center - Overland Park
    • Overland Park, Kansas, United States, 66211
      • Recruiting
      • The University of Kansas Cancer Center - Indian Creek Campus
    • Westwood, Kansas, United States, 66205
      • Recruiting
      • The University of Kansas Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Recruiting
      • Norton Cancer Institute, St. Matthews Campus
    • Louisville, Kentucky, United States, 40207
      • Recruiting
      • Norton Cancer Institute, St. Matthews Campus, Attn. Becky Champion, PharmD
    • Louisville, Kentucky, United States, 40207
      • Recruiting
      • Norton Women & Children's Hospital
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Norton Hospitals, Inc
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Meghan Burke; Phone Number: 617-726-1599; Email: MBURKE19@PARTNERS.ORG
      • Principal Investigator: Amir Fathi
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: Jessica Liegel; Phone Number: 617-667-9922; Email: jliegel@bidmc.harvard.edu
      • Principal Investigator: Malgorzata McMasters
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber/Mass General Brigham Cancer Care, Inc
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Karmanos Cancer Institute
    • Farmington Hills, Michigan, United States, 48334
      • Recruiting
      • Karmanos Cancer Institute Weisberg Cancer Treatment Center
  • Missouri
    • Kansas City, Missouri, United States, 64116
      • Recruiting
      • The University of Kansas Cancer Center - Medical Oncology Clinic
    • Kansas City, Missouri, United States, 64116
      • Recruiting
      • The University of Kansas Cancer Center - Radiation Oncology Clinic
    • Kansas City, Missouri, United States, 64154
      • Recruiting
      • The University of Kansas Cancer Center -North
    • Lee's Summit, Missouri, United States, 64064
      • Recruiting
      • The University of Kansas Cancer Center - Lee's Summit
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center
    • New York, New York, United States, 10032
      • Recruiting
      • The New York and Presbyterian Hospital
    • New York, New York, United States, 10032
      • Recruiting
      • CUIMC Research Pharmacy
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals Cleveland Medical Center
      • Contact: Susan Ackerman; Phone Number: 216-286-4150; Email: Susan.Ackerman2@uhhospitals.org
      • Principal Investigator: Benjamin K Tomlinson
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University Wexner Medical Center/James Cancer Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Hollings Cancer Center
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina- Ashley River Tower
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina- Investigational Drug Services
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina- University Hospital
  • Texas
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Baylor University Medical Center
    • Dallas, Texas, United States, 75204
      • Recruiting
      • Baylor Research Institute
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Baylor University Medical Center, Investigational Drug Services, Department of Pharmacy
    • Houston, Texas, United States, 77030
      • Recruiting
      • Houston Methodist Hospital
    • Houston, Texas, United States, 77030
      • Active, not recruiting
      • The University of Texas MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Recruiting
      • Swedish Cancer Institute
      • Contact: Neil Bailey; Phone Number: 206-386-6000; Email: neil.bailey@swedish.org
      • Principal Investigator: Daniel Egan
    • Seattle, Washington, United States, 98122
      • Recruiting
      • Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A; SEA-CD70 dose escalation cohort in relapsed/refractory (HMA-failure) MDS	Drug: SEA-CD70; Given into the vein (IV; intravenously) on Days 1 and 15 of each treatment cycle
Experimental: Part B; SEA-CD70 expansion cohort in relapsed/refractory (HMA-failure) MDS	Drug: SEA-CD70; Given into the vein (IV; intravenously) on Days 1 and 15 of each treatment cycle
Experimental: Part C; SEA-CD70 expansion cohort in relapsed/refractory AML	Drug: SEA-CD70; Given into the vein (IV; intravenously) on Days 1 and 15 of each treatment cycle
Experimental: Part D; SEA-CD70 + azacitidine dose-finding/dose optimization cohorts in relapsed/refractory MDS or MDS/AML, and previously untreated higher-risk MDS or MDS/AML	Drug: SEA-CD70; Given into the vein (IV; intravenously) on Days 1 and 15 of each treatment cycle; Drug: azacitidine; 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
Experimental: Part E; SEA-CD70 + azacitidine expansion cohort in previously untreated higher-risk MDS or MDS/AML	Drug: SEA-CD70; Given into the vein (IV; intravenously) on Days 1 and 15 of each treatment cycle; Drug: azacitidine; 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
Experimental: Part F; SEA-CD70 + azacitidine expansion cohort in relapsed/refractory MDS or MDS/AML	Drug: SEA-CD70; Given into the vein (IV; intravenously) on Days 1 and 15 of each treatment cycle; Drug: azacitidine; 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
Experimental: Part G; SEA-CD70 + azacitidine +venetoclax dose-finding/dose optimization in previously untreated and unfit for induction therapy AML	Drug: SEA-CD70; Given into the vein (IV; intravenously) on Days 1 and 15 of each treatment cycle; Drug: azacitidine; 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; Drug: Venetoclax; 400 mg /day PO, continuously; administered with ramping; Other Names: Venclexta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs)	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.	Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Number of participants with laboratory abnormalities	To be summarized using descriptive statistics.	Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Number of participants with a dose-limiting toxicity (DLT) at each dose level (Parts A and D only)	To be summarized using descriptive statistics.	Though end of DLT evaluation period; up to approximately 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC - Area under the plasma concentration-time curve	To be summarized using descriptive statistics.	Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Tmax - Time to maximum concentration attained	To be summarized using descriptive statistics.	Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Cmax - Maximum observed plasma concentration	To be summarized using descriptive statistics.	Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Ctrough - Minimum plasma concentration per dosing interval	To be summarized using descriptive statistics.	Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
T1/2 - Terminal elimination half-life	To be summarized using descriptive statistics.	Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Incidence of antidrug antibodies (ADA)	To be summarized using descriptive statistics.	Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Complete remission with incomplete blood count recovery (CRi) rate	Proportion of participants with AML who achieve CRi	Up to approximately 4 years
Overall survival (OS)	Time from start of study treatment to the date of death due to any cause	Up to approximately 4 years
Time to response (TTR)	Time from start of study treatment to the first documentation of objective response	Up to approximately 4 years
Rate of conversion to transfusion independence (TI)	Proportion of participants who convert from transfusion dependence at baseline to TI post-baseline	Up to approximately 4 years
Rate of TI maintenance	Proportion of participants who were TI at baseline and maintain TI post-baseline	Up to approximately 4 years
Complete remission (CR) Rate and complete remission equivalent (CReq) rate	Proportion of participants with AML, MDS/AML or MDS who achieve CR or CReq	Up to approximately 4 years
Complete remission with limited count recovery (CRL) rate for participants with MDS or MDS/AML	Proportion of participants with MDS or MDS/AML who achieve CRL	Up to approximately 4 years
Complete remission with partial hematologic recovery (CRh) rate	Proportion of participants with AML, MDS/AML, or MDS who achieve CRh	Up to approximately 4 years
Hematologic response (HI) rate	Proportion of participants with MDS or MDS/AML with HI	Up to approximately 4 years
Overall response rate (ORR)	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	Up to approximately 4 years
Duration of remission (DOR)	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	Up to approximately 4 years
Event-free survival (EFS)	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.	Up to approximately 4 years
Progression-free survival (PFS)	Time from first dose to the first documentation of progression, disease relapse, or death from any cause, whichever comes first	Up to approximately 4 years
MRD-negative ORR	Proportion of participants with AML or MDS who achieve MRD-negative ORR	Up to approximately 4 years

Collaborators and Investigators

• Sponsor: Seagen, a wholly owned subsidiary of Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

General Publications

• Dewulf J, Flieswasser T, Delahaye T, Vangestel C, Miranda A, de Haard H, Jacobs J, Smits E, Van den Wyngaert T, Elvas F. Site-specific 68Ga-labeled nanobody for PET imaging of CD70 expression in preclinical tumor models. EJNMMI Radiopharm Chem. 2023 Apr 24;8(1):8. doi: 10.1186/s41181-023-00194-3.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2020
• Primary Completion (Estimated): July 4, 2027
• Study Completion (Estimated): July 3, 2028

Study Registration Dates

• First Submitted: January 10, 2020
• First Submitted That Met QC Criteria: January 10, 2020
• First Posted (Actual): January 14, 2020

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Seattle Genetics
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; venetoclax
• Other Study ID Numbers: SGNS70-101; C5781001 (Other Identifier: Alias Study Number); 2023-506945-42-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No