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: May 10, 2022
• 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; 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

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 ]
   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 (Part A only) [ Time Frame: Though end of DLT evaluation period; up to approximately 4 weeks ]
   To be summarized using descriptive statistics.

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 ]
   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 [ 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, CRh, 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, or 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, or CRh 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 marrow 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 HMA) or 4 cycles of decitabine (or equivalent 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 HMA therapy ≥ 2 weeks and must be off any other treatments for MDS for ≥ 4 weeks prior to first dose of SEA-CD70; 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 HMA therapy ≥ 2 weeks and must be off any other systemic treatments for MDS for ≥ 4 weeks prior to first dose of SEA-CD70; growth factors (e.g., G-CSF, erythropoietin and thrombopoietin) and transfusions are allowed before and during the study as clinically indicated.
• 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
• History of clinically significant sickle cell anemia, autoimmune hemolytic anemia, or idiopathic thrombocytopenic purpura

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, 91010-3000

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

Principal Investigator: Ahmed M 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, Kentucky

Norton Cancer Institute; Recruiting

Louisville, Kentucky, United States, 40207

Contact: Joshua Roberts 502-899-2673

Principal Investigator: Don A Stevens

United States, Massachusetts

Massachusetts General Hospital; Recruiting

Boston, Massachusetts, United States, 02114

Contact: Meghan Burke 617-726-1599

Principal Investigator: Amir Fathi

Beth Israel Deaconess Medical Center; Recruiting

Boston, Massachusetts, United States, 02215

Contact: Kayla Loycano 617-667-9920

Principal Investigator: Jessica Liegel

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 K Tomlinson

Cleveland Clinic, The; Recruiting

Cleveland, Ohio, United States, 44195

Contact: Taussig Research group email 866-223-8100 TaussigResearch@ccf.org

Principal Investigator: Anjali Advani

James Cancer Hospital / Ohio State University; Recruiting

Columbus, Ohio, United States, 43210

Contact: Shayla Thompson 614-293-5655

Principal Investigator: Alice Mims

Principal Investigator: Nicole Grieselhuber

United States, South Carolina

Medical University of South Carolina/Hollings Cancer Center; Recruiting

Charleston, South Carolina, United States, 29425

Contact: Shanta Salzer 843-792-1463

Principal Investigator: Robert K Stuart

Principal Investigator: Praneeth Baratam

Saint Francis Hospital / Bon Secours - South Carolina; Recruiting

Greenville, South Carolina, United States, 29607

Contact: Sharon (Nikki) N Thompson 864-603-6238

Principal Investigator: Howland Crosswell

Principal Investigator: Sharif S Khan

United States, Tennessee

Tennessee Oncology-Nashville/Sarah Cannon Research Institute; Completed

Nashville, Tennessee, United States, 37203

United States, Texas

Texas Oncology - Fort Worth; Recruiting

Dallas, Texas, United States, 75246

Contact: Joyce Ghormley 214-818-8961

Principal Investigator: Edward J Pearson

MD Anderson Cancer Center / University of Texas; Recruiting

Houston, Texas, United States, 77030-4095

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

Principal Investigator: Guillermo Garcia-Manero

Netherlands

Leids Universitair Medisch Centrum ( LUMC); Recruiting

Leiden, Other, Netherlands, 2333 ZA

Principal Investigator: Hendrik J Veelken

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: May 10, 2022
• Last Verified: May 2022

• 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