This is a Phase 2 study to evaluate the efficacy, safety, and tolerability of axatilimab at 3 different dose levels in participants with recurrent or refractory active chronic graft versus host disease (cGVHD) who have received at least 2 prior lines of systemic therapy.
AGAVE-201 is a Phase 2, open-label, randomized, multicenter study to evaluate the efficacy, safety, and tolerability of axatilimab in participants with recurrent or refractory active cGVHD after failure of at least 2 prior lines of systemic therapy due to progression of disease, intolerability, or toxicity. Participants will be randomized to receive 1 of 3 different axatilimab treatment regimens in 28-day treatment cycles for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
241
Axatilimab is a high-affinity antibody targeting the colony stimulating factor 1 receptor (CSF-1R). CSF-1R signaling has been demonstrated in nonclinical studies to be the key regulatory pathway involved in the expansion and infiltration of donor-derived macrophages that mediate the disease processes involved in cGVHD.
Overall Response Rate (ORR) in the First 6 Cycles as Defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-Versus-Host Disease (cGVHD)
The ORR was defined as the percentage of participants with objective response (complete response \[CR\] or partial response \[PR\]). CR was defined as resolution of all manifestations in each organ or site, and PR was defined as improvement in at least 1 organ or site without progression in any other organ or site.
Time frame: First 6 cycles (up to Cycle 7 Day 1; each cycle = 4 weeks)
ORR on Study as Defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD
Time frame: Up to 2 years
Number of Participants With a Clinically Significant Improvement in Normalized Score on the Modified Lee Symptom Scale
Time frame: Up to 2 years
Duration of Response
Duration of response is defined as the time from initial partial response or complete response until documented progression of cGVHD, start of new therapy, or death for any reason.
Time frame: Up to 2 years
Sustained Response Rate
Sustained response rate is defined as the number of participants with objective response lasting for at least 20 weeks (140 days) from the time of initial response. Responses will be assessed based on the 2014 NIH Consensus Development Project on Clinical Trials in cGVHD.
Time frame: Up to 2 years
Organ-specific Response Rate
Organ-specific response is defined as the number of participants with objective response for the nine individual organs based on 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD (skin, eyes, mouth, esophagus, upper gastrointestinal \[GI\], lower GI, liver, lungs and joints and fascia).
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University of Alabama at Birmingham - Children's of Alabama
Birmingham, Alabama, United States
University of Alabama at Birmingham
Birmingham, Alabama, United States
City of Hope
Duarte, California, United States
University of Southern California Norris Comprehensive Cancer Center
Los Angeles, California, United States
University of California, Los Angeles (UCLA) - Medical Center
Los Angeles, California, United States
Stanford Cancer Center
Stanford, California, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
University of Florida (UF)
Gainesville, Florida, United States
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States
University of Miami
Miami, Florida, United States
...and 111 more locations
Time frame: Up to 2 years
Joints and Fascia Response Rate Based on Refined NIH Response Algorithm for cGVHD
Time frame: Up to 2 years
Percent Reductions in Average Daily Doses (or Equivalent) of Corticosteroid
Time frame: Up to 2 years
Number of Participants Who Discontinue Corticosteroid Use
Time frame: Up to 2 years
Percent Reductions in Average Daily Doses (or Equivalent) of Calcineurin Inhibitors (CNI)
Time frame: Up to 2 years
Number of Participants Who Discontinue CNIs
Time frame: Up to 2 years
Change From Baseline in Circulating Monocyte Number and Phenotype (CD14/16)
Time frame: Baseline, up to 2 years
Number of Participants With Anti-Drug Antibody
Time frame: Up to 2 years
Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of Last Measurable Concentration (AUC0-t)
Time frame: Approximately 12 months
Number of Participants With Treatment-emergent Adverse Events
Time frame: Up to 2 years
Change From Baseline in Bone Turnover Markers
Time frame: Baseline, up to 2 years
Change From Baseline in Bone Density
Time frame: Baseline, up to 2 years
Change From Baseline in Colony Stimulating Factor 1 (CSF-1) and Interleukin 34 (IL-34) Levels
Time frame: Baseline, up to 2 years