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

• ClinicalTrials.gov Identifier: NCT04227847
• Recruitment Status: Recruiting
• First Posted: January 14, 2020
• Last Update Posted: December 9, 2020
• Sponsor: Seagen Inc.
• Information provided by (Responsible Party): Seagen Inc.

Study Description

Brief Summary:

This trial will look at a drug called SEA-CD70 to find out if it is safe for patients 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 three groups or "parts." Part A will find out how much SEA-CD70 should be given to patients. Part B will use the dose found in Part A to find out how safe SEA-CD70 is and if it works to treat patients 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 patients with AML.

Condition or disease	Intervention/treatment	Phase
Myelodyspastic Syndrome; Acute Myeloid Leukemia	Drug: SEA-CD70	Phase 1

Detailed Description:

This is a phase 1, open-label, multicenter, dose-escalation, and cohort expansion study designed to evaluate the safety, tolerability, PK, and antitumor activity of SEA-CD70 in adults with myeloid malignancies. The study will be conducted in up to 3 parts.

Part A is a dose escalation cohort designed to identify the MTD or recommended expansion dose of SEA-CD70 in subjects with relapsed/refractory (HMA-failure) MDS. Part B is an expansion cohort designed to evaluate the safety and tolerability of SEA-CD70 in subjects with relapsed/refractory (HMA-failure) MDS. Part C is an expansion cohort designed to evaluate the safety and tolerability of SEA-CD70 in subjects with relapsed/refractory AML.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Part B and C will enroll in parallel after enrollment of Part A is complete.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study of SEA-CD70 in Myeloid Malignancies
• Actual Study Start Date: August 7, 2020
• Estimated Primary Completion Date: November 30, 2022
• Estimated Study Completion Date: October 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part A; SEA-CD70 dose escalation cohort in relapsed/refractory (HMA-failure) MDS	Drug: SEA-CD70; Intravenous (IV) infusion 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; Intravenous (IV) infusion on Days 1 and 15 of each treatment cycle
Experimental: Part C; SEA-CD70 expansion cohort in relapsed/refractory AML	Drug: SEA-CD70; Intravenous (IV) infusion on Days 1 and 15 of each treatment cycle

Outcome Measures

Primary Outcome Measures :

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 ]
2. Number of participants with laboratory abnormalities [ Time Frame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years ]
3. Number of participants with a dose-limiting toxicity (DLT) at each dose level (Part A only) [ Time Frame: Though end of DLT evaluation period; up to approximately 4 weeks ]

Secondary Outcome Measures :

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 ]
2. Tmax - Time to maximum concentration attained [ Time Frame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years ]
3. Cmax - Maximum observed plasma concentration [ Time Frame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years ]
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 ]
5. T1/2 - Terminal elimination half-life [ Time Frame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years ]
6. Incidence of antidrug antibodies (ADA) [ Time Frame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years ]
7. Complete remission (CR) Rate [ Time Frame: Up to approximately 4 years ]
   Proportion of participants with AML or MDS who achieve CR
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 partial hematologic recovery (CRh) rate [ Time Frame: Up to approximately 4 years ]
   Proportion of participants with AML or MDS who achieve CRh
10. Hematologic response (HI) rate [ Time Frame: Up to approximately 4 years ]
    Proportion of MDS participants with HI
11. Objective 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 or PR.
12. Blast clearance rate for participants with MDS [ Time Frame: Up to approximately 4 years ]
    Proportion of participants with MDS who achieve CR, PR, Marrow CR, or CRh
13. Duration of response (DOR) [ Time Frame: Up to approximately 4 years ]
    For AML, the time from first CR/CRi/CRh response to the first documentation of disease progression, start of new therapy, or death due to any cause. For MDS, the time from first PR/CR to the first documentation of disease progression, start of new 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, disease relapse, or death due to any cause, whichever comes first.
16. MRD-negative ORR [ Time Frame: Up to approximately 4 years ]
    Proporation of participants with AML or MDS who achieve MRD-negative ORR
17. Time to response (TTR) [ Time Frame: Up to approximately 4 years ]
    Time from start of study treatment to the first documentation of objective response
18. 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
19. Maintenance of TI [ Time Frame: Up to approximately 4 years ]
    Number of subjects who were TI at baseline and maintain TI post-baseline

Eligibility Criteria

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

Criteria

Part A Inclusion Criteria

• Participants with cytologically/histologically confirmed myelodysplastic syndrome (MDS) according to the 2016 World Health Organization (WHO) classification with the following:

  • Measurable disease per WHO MDS with excess blasts criteria as defined either:

    • 5%-9% blasts in the bone marrow Or 2%-4% blasts in the peripheral blood or
    • 10%-19% blasts in the bone marriw or 5%-19% blasts in the peripheral blood
  • MDS that is relapsed or refractory and must not have other therapeutic options known to provide clinical benefit in MDS available.

  • Treatment failure after prior hypomethylating agent (HMA) therapy for MDS, defined as one of the following:

    • Progression (per 2006 International Working Group [IWG] criteria) at any time after initiation of HMA therapy.
    • Lack of response (failure to achieve complete remission [CR], partial response [PR], or hematologic improvement [HI] per 2006 IWG criteria) after at least 6 cycles of azacitidine (or equivalent oral HMA) or 4 cycles of decitabine (or equivalent oral HMA).
    • Relapse after achievement of CR, PR, or HI (per 2006 IWG criteria).
    • Intolerance of HMA (Grade 3 or higher non-hematologic toxicity leading to treatment discontinuation).
    • Participants with isolated 5q-/5q- syndrome must have progressed, failed, relapsed, or not tolerated lenalidomide in addition to HMA.
• Must be off all treatments for MDS for ≥ 4 weeks; growth factors and transfusions are allowed before and during the study as clinically indicated
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

Part B Inclusion Criteria

• Participants with cytologically/histologically confirmed MDS according to the WHO classification with the following:

  • Measurable disease per WHO MDS with excess blasts (MDS-EB) criteria as defined either:

    • 5%-9% blasts in the bone marrow or 2%-4% blasts in the peripheral blood, or
    • 10%-19% blasts in the bone marrow or 5%-19% in the peripheral blood
  • MDS that is relapsed or refractory and must not have other therapeutic options known to provide clinical benefit in MDS available.

  • Treatment failure after prior HMA therapy for MDS defined as one of the following:

    • Progression (per 2006 IWG criteria) at any time after initiation of HMA therapy.
    • Lack of response (failure to achieve CR, PR, or HI per 2006 IWG criteria) after at least 6 cycles of azacitidine or 4 cycles of decitabine.
    • Relapse after achievement of CR, PR, or HI (per 2006 IWG criteria).
    • Intolerance of HMA (Grade 3 or higher non-hematologic toxicity leading to treatment discontinuation).
    • Participants with isolated 5q-/5q- syndrome must have progressed, failed, relapsed, or not tolerated lenalidomide in addition to HMA.
• Must be off all treatments for MDS (including HMAs) for ≥ 4 weeks; growth factors (e.g., G-CSF, erythropoietin and thrombopoietin) and transfusions are allowed before and during the study as clinically indicated.
• At least one cytopenia (absolute neutrophil count [ANC] <1800/μL or platelet count <100,000/μL or hemoglobin [Hgb] <10 g/dL).
• ECOG Performance Status of 0-2

Part C Inclusion Criteria

• Participants with relapsed or refractory acute myeloid leukemia (AML) according to the WHO 2016 classification (except for acute promyelocytic leukemia [APL]):

  • Who have received either 2 or 3 previous regimens to treat active disease. Post-remission treatments, intrathecal chemotherapy, and radiotherapy are not considered 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 (defined as failure to achieve CR after 1-2 courses of induction therapy)
    • First CR duration <6 months
    • Adverse-risk per European Leukemia Net (ELN) genetic risk stratification
    • Secondary AML (prior history of MDS or therapy-related)
• Age 18-75 years
• ECOG performance status of 0-2

Exclusion Criteria (All Parts)

• History of another malignancy within 3 years before the first dose of study drug or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death.
• Previous exposure to CD70-targeted agents
• Prior allogeneic hematopoietic stem cell transplant, for any condition
• Central nervous system leukemia based on imaging or documented positive cytology in cerebral spinal fluid
• Any uncontrolled Grade 3 or higher viral, bacterial, or fungal infection within 14 days prior to the first dose of study treatment. Antimicrobial prophylaxis or ongoing treatment of resolving/controlled infection is permitted.
• Participants who have experienced major surgery (defined as requiring general anesthesia and hospitalization for >24 hours) or significant traumatic injury that would place the participant at undue risk from study procedures, in the opinion of the investigator, within 14 days before the first dose of study treatment.
• Positive for hepatitis B by surface antigen expression. Active hepatitis C infection (positive by PCR or on antiviral therapy for hepatitis C within the last 6 months). Participants who have been treated for hepatitis C infection are permitted if they have documented sustained virologic response of 12 weeks.
• Known to be positive for human immunodeficiency virus (HIV)
• Known active or latent tuberculosis
• History of clinically significant sickle cell anemia, autoimmune hemolytic anemia, or idiopathic thrombocytopenic purpura
• History of clinically significant chronic liver disease (e.g. liver cirrhosis) and/or ongoing alcohol abuse
• Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association Class III-IV within 6 months prior to their first dose of SEA-CD70.
• Chemotherapy, systemic radiotherapy, biologics, other anti-neoplastic or investigational agents, and/or other antitumor treatment with immunotherapy that is not completed 4 weeks prior to first dose of SEA-CD70. Focal radiotherapy that is not completed 2 weeks prior to the first dose of SEA-CD70. Hydroxyurea or 6-mercaptopurine used for cytoreduction may be given up to 24 hours prior to treatment.

• Participants with either of the following:

  • A condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 2 weeks of first dose of SEA-CD70
  • Active known or suspected clinically significant autoimmune disease or clinically significant autoimmune-related toxicity from prior immuno-oncology-based therapy
• Known hypersensitivity to any excipient contained in the drug formulation of SEA-CD70
• Estimated life expectancy <12 weeks

Contacts and Locations

Contacts

Contact: Seagen Trial Information Support; 866-333-7436; clinicaltrials@seagen.com

Locations

United States, Alabama

University of Alabama at Birmingham; Recruiting

Birmingham, Alabama, United States, 35249

Contact: Hilary Avery 205-934-7167 hilaryavery@uabmc.edu

Principal Investigator: Pankit Vachhani

United States, California

City of Hope National Medical Center; Recruiting

Duarte, California, United States, 91010

Contact: Lucia Magos 626-256-4673 lmagos@coh.org

Principal Investigator: Ahmed Aribi

United States, Colorado

Colorado Blood Cancer Institute; Recruiting

Denver, Colorado, United States, 80218

Contact: James Vick 720-754-4800 James.Vick@sarahcannon.com

Principal Investigator: Marcello Rotta

United States, Michigan

Karmanos Cancer Institute / Wayne State University; Recruiting

Detroit, Michigan, United States, 48201

Contact: Mary Domagalski 313-576-9767 domagalm@karmanos.org

Principal Investigator: Jay Yang

United States, Ohio

Case Western Reserve University / University Hospitals Cleveland Medical Center; Recruiting

Cleveland, Ohio, United States, 44106

Contact: Sarah Housour 216-286-7082 Sarah.Housour@uhhospitals.org

Principal Investigator: Benjamin Tomlinson

The Cleveland Clinic; Recruiting

Cleveland, Ohio, United States, 44195

Contact: Taussig Research TaussigResearch@ccf.org

Principal Investigator: Anjali Advani

United States, Tennessee

Tennessee Oncology-Nashville/Sarah Cannon Research Institute; Recruiting

Nashville, Tennessee, United States, 37203

Contact: Matthew Price 615-524-4100 Matthew.Price@SarahCannon.com

Principal Investigator: William Donnellan

United States, Texas

MD Anderson Cancer Center / University of Texas; Recruiting

Houston, Texas, United States, 77030

Contact: Heather Schneider 713-792-4478 hnschneider@mdanderson.org

Principal Investigator: Guillermo Garcia-Manero

Sponsors and Collaborators

Seagen Inc.

Investigators

• Study Director: Phoenix Ho, MD; Seagen Inc.

More Information

• Responsible Party: Seagen Inc.
• ClinicalTrials.gov Identifier: NCT04227847
• Other Study ID Numbers: SGNS70-101; 2019-001917-18 ( EudraCT Number )
• First Posted: January 14, 2020
• Last Update Posted: December 9, 2020
• Last Verified: December 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Seagen Inc.:

Seattle Genetics