Clinical trial NCT04227847: A Safety Study of SEA-CD70 in Patients With Myeloid Malignancies
Official title: A Phase 1 Study of SEA-CD70 in Myeloid Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Myelodysplastic Syndrome
Acute Myeloid Leukemia
Keywords: Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2020-01-14
Enrollment: 178
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Parts B and C may enroll in parallel after enrollment of Part A is complete. Part D will enroll after Part A is complete. Parts E, F and Part G will enroll in parallel once Part D is complete.
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
measure: Number of participants with laboratory abnormalities
timeFrame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
measure: Number of participants with a dose-limiting toxicity (DLT) at each dose level (Parts A and D only)
timeFrame: Though end of DLT evaluation period; up to approximately 4 weeks
Secondary outcomes:
measure: AUC - Area under the plasma concentration-time curve
timeFrame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
measure: Tmax - Time to maximum concentration attained
timeFrame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
measure: Cmax - Maximum observed plasma concentration
timeFrame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
measure: Ctrough - Minimum plasma concentration per dosing interval
timeFrame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
measure: T1/2 - Terminal elimination half-life
timeFrame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
measure: Incidence of antidrug antibodies (ADA)
timeFrame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
measure: Complete remission (CR) Rate and complete remission equivalent (CReq) rate
timeFrame: Up to approximately 4 years
measure: Complete remission with incomplete blood count recovery (CRi) rate
timeFrame: Up to approximately 4 years
measure: Complete remission with limited count recovery (CRL) rate for participants with MDS or MDS/AML
timeFrame: Up to approximately 4 years
measure: Complete remission with partial hematologic recovery (CRh) rate
timeFrame: Up to approximately 4 years
measure: Hematologic response (HI) rate
timeFrame: Up to approximately 4 years
measure: Overall response rate (ORR)
timeFrame: Up to approximately 4 years
measure: Duration of remission (DOR)
timeFrame: Up to approximately 4 years
measure: Overall survival (OS)
timeFrame: Up to approximately 4 years
measure: Event-free survival (EFS)
timeFrame: Up to approximately 4 years
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 4 years
measure: MRD-negative ORR
timeFrame: Up to approximately 4 years
measure: Time to response (TTR)
timeFrame: Up to approximately 4 years
measure: Rate of conversion to transfusion independence (TI)
timeFrame: Up to approximately 4 years
measure: Rate of TI maintenance
timeFrame: Up to approximately 4 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Birmingham
country: United States
facility: ONeal Comprehensive Cancer Center at UAB
state: Alabama
city: Duarte
country: United States
facility: City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
state: California
city: Duarte
country: United States
facility: IP Address: City of Hope Investigational Drug Services(IDS)
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Department of Medicine - Hematology & Oncology
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology-Oncology Clinic
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute, Lab
state: Colorado
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Denver
country: United States
facility: Presbyterian/St. Luke's Medical Center
state: Colorado
city: Fairway
country: United States
facility: The University of Kansas Cancer Center ,Investigational Drug Services
state: Kansas
city: Fairway
country: United States
facility: The University of Kansas Clinical Research Center
state: Kansas
city: Kansas City
country: United States
facility: The University of Kansas Hospital
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Hospital Cambridge North Tower A
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Medical center Medical office building
state: Kansas
city: Overland Park
country: United States
facility: The University of Kansas Cancer Center - Overland Park
state: Kansas
city: Overland Park
country: United States
facility: The University of Kansas Cancer Center - Indian Creek Campus
state: Kansas
city: Louisville
country: United States
facility: Norton Cancer Institute, St. Matthews Campus, Attn. Becky Champion, PharmD
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute, St. Matthews Campus
state: Kentucky
city: Louisville
country: United States
facility: Norton Women & Children's Hospital
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Farmington Hills
country: United States
facility: Karmanos Cancer Institute Weisberg Cancer Treatment Center
state: Michigan
city: Kansas City
country: United States
facility: The University of Kansas Cancer Center - Medical Oncology Clinic
state: Missouri
city: Kansas City
country: United States
facility: The University of Kansas Cancer Center - Radiation Oncology Clinic
state: Missouri
city: Kansas City
country: United States
facility: The University of Kansas Cancer Center -North
state: Missouri
city: Lee's Summit
country: United States
facility: The University of Kansas Cancer Center - Lee's Summit
state: Missouri
city: Farmington
country: United States
facility: San Juan Oncology Associates
state: New Mexico
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: New York
country: United States
facility: CUIMC Research Pharmacy
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: James Cancer Hospital / Ohio State University
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center/James Cancer Hospital
state: Ohio
city: Charleston
country: United States
facility: Hollings Cancer Center
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina- Ashley River Tower
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina- Investigational Drug Services
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina- University Hospital
state: South Carolina
city: Greenville
country: United States
facility: St. Francis Hospital
state: South Carolina
city: Greenville
country: United States
facility: St. Francis Cancer Center
state: South Carolina
city: Dallas
country: United States
facility: Baylor University Medical Center, Investigational Drug Services, Department of Pharmacy
state: Texas
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Utrecht
country: Netherlands
facility: Pharmacy - UMC Utrecht t.a.v. Apotheek KGO
city: Utrecht
country: Netherlands
facility: University Medical Center (UMC) Utrecht
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: