The main purpose of this study are to determine the recommended Phase 2 dose(s) (RP2D) route of administration, schedule and the maximum tolerated dose (MTD) in Part 1 and to determine the safety and tolerability of JNJ-67571244 at the RP2D regimen(s) and to evaluate the preliminary clinical activity of JNJ-67571244 in Part 2.
This is first-in-human (FIH) Phase 1, open-label, multicenter, dose escalation study with dose expansion to evaluate the safety, tolerability, and preliminary antitumor activity of JNJ-67571244 in adult participants with relapsed or refractory acute myeloid leukemia (AML) or high-risk or very high-risk myelodysplastic syndromes (MDS) who are ineligible for or have exhausted standard therapeutic options. The study is divided into 3 periods: a Screening Phase (within 28 days before the first dose of study drug), a Treatment Phase (first dose of study drug until the last dose of study drug) and a Post-treatment Follow-up Phase (up to the end of study participation or end of study). Duration of study is 2.3 years.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
68
JNJ-67571244 will be administered.
Massachusetts General Hospital
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Part 1 and Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Time frame: Up to 100 days after the last dose of study drug or until the start of a subsequent anticancer therapy, whichever comes first (that is up to 2.3 years)
Part 1: Number of Participants with Dose-Limiting Toxicity (DLTs)
Number of participants with dose-limiting toxicity will be assessed. The DLTs are based on drug-related adverse events and defined as any of the following events: infusion-related reactions, non-hematologic toxicity of Grade 3 or higher, or hematologic toxicity.
Time frame: Up to 28 days
Part 1: Severity of DLT as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
The DLT evaluation period is defined as the first 28 days after a participant's first infusion (Day 1). Severity criteria is based on Grade 1, 2, 3, 4 and 5, will be assessed by the investigator as per below grades. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening consequences; Grade 5: Death related to adverse event.
Time frame: Up to 28 days
Part 2: Overall Response Rate (ORR)
ORR is defined as the percentage of participants who have complete response (CR) and incomplete blood count recovery (CRi) (AML) or CR and partial response (PR) (MDS) as per modified International Working Group response (IWGR) criteria.
Time frame: Approximately 2.3 years
Part 1 and Part 2: Serum Concentrations of JNJ-67571244
Serum samples will be analyzed to determine concentrations of JNJ-67571244 using a validated immunoassay method.
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Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
NYU Hematology Associates
New York, New York, United States
Levine Cancer Institute, Carolinas HealthCare System
Charlotte, North Carolina, United States
Sarah Cannon Research Institute
Nashville, Tennessee, United States
MD Anderson Cancer Center
Houston, Texas, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States
Universitaetsklinikum Leipzig
Leipzig, Germany
...and 7 more locations
Time frame: Approximately 2.3 years
Part 1 and 2: Systemic Cytokine Concentrations
Serum cytokine (Interleukin \[IL\]-2, IL-6, IL-8, IL-10, and Interferon \[IFN\]-alpha, IFN-delta with same unit of measurement) concentrations will be measured for biomarker assessment.
Time frame: Approximately 2.3 years
Number of Participants with Depletion of CD33-Expressing Cells
Number of participants with depletion of CD33-expressing cells will be assessed.
Time frame: Approximately 2.3 years
Part 1 and 2: Concentration of Markers of T-Cell Activation
Levels of T-cell activation marker CD25 will be reported as measured by flow cytometry and cytometry by time of flight (CyTOF). T-cell activation will also be assessed by measuring cytokine release.
Time frame: Up to 24 days
Part 1 and 2: Number of Participants with JNJ-67571244 Antibodies
Anti-JNJ-67571244 antibodies will be evaluated in serum samples collected from all participants and the titer of confirmed positive samples will be reported.
Time frame: Week 1 (Day 1) up to post treatment Week 8
Part 1 and Part 2: Duration of response (DOR)
DOR is calculated from date of initial documentation of a response (complete response (CR) and incomplete blood count recovery (CRi) (AML) or CR and partial response (PR) \[MDS\]) to the date of first documented evidence of relapse, defined in disease-specific response criteria, or death, whichever occurs first.
Time frame: Approximately 2.3 years
Part 1 and Part 2: Time to response (TTR)
TTR defined for the responders as the time from the date of first dose of study drug to the date of initial documentation of a response (CR and CRi \[AML\] or CR and PR \[MDS\]), as defined in the disease-specific response criteria.
Time frame: Approximately 2.3 years