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 compared to azacitidine alone 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.
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 vs 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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
170
Given into the vein (IV; intravenously) on Days 1 and 15 of each treatment cycle
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.
400 mg /day PO, continuously; administered with ramping
University of Alabama at Birmingham
Birmingham, Alabama, United States
University of Alabama at Birmingham
Birmingham, Alabama, United States
Dept. of Medicine, UAB ONeal Comprehensive Cancer Center
Birmingham, Alabama, United States
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
Duarte, California, United States
IP Address: City of Hope Investigational Drug Services(IDS)
Duarte, California, United States
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.
Time frame: 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.
Time frame: 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.
Time frame: Though end of DLT evaluation period; up to approximately 4 weeks
AUC - Area under the plasma concentration-time curve
To be summarized using descriptive statistics.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Through 30-37 days following last dose of SEA-CD70; up to approximately 2 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
Time frame: Up to approximately 4 years
Complete remission with incomplete blood count recovery (CRi) rate
Proportion of participants with AML who achieve CRi
Time frame: 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
Time frame: 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
Time frame: Up to approximately 4 years
Hematologic response (HI) rate
Proportion of participants with MDS or MDS/AML with HI
Time frame: 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
Time frame: 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
Time frame: Up to approximately 4 years
Overall survival (OS)
Time from start of study treatment to the date of death due to any cause
Time frame: 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.
Time frame: 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
Time frame: Up to approximately 4 years
MRD-negative ORR
Proportion of participants with AML or MDS who achieve MRD-negative ORR
Time frame: Up to approximately 4 years
Time to response (TTR)
Time from start of study treatment to the first documentation of objective response
Time frame: 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
Time frame: Up to approximately 4 years
Rate of TI maintenance
Proportion of participants who were TI at baseline and maintain TI post-baseline
Time frame: Up to approximately 4 years
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Ronald Reagan UCLA Medical Center
Los Angeles, California, United States
UCLA Hematology-Oncology Clinic
Los Angeles, California, United States
Colorado Blood Cancer Institute, Lab
Denver, Colorado, United States
Colorado Blood Cancer Institute
Denver, Colorado, United States
Presbyterian/St. Luke's Medical Center
Denver, Colorado, United States
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