This is a phase I, multicenter, open-label, dose-escalation study of cevostamab administered as a single agent by IV infusion to participants with relapsed or refractory multiple myeloma (R/R MM).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
355
Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
Tocilizumab will be administered as premedication during Cycle 1.
University of Alabama at Birmingham
Birmingham, Alabama, United States
Mayo Clinic Hospital - Arizona
Scottsdale, Arizona, United States
Percentage of Participants with Adverse Events (AEs)
An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Time frame: Up to approximately 8 years
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Dose-Limiting Toxicities (DLTs) will be reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), except for Cytokine release syndrome (CRS), which will be graded according to the American Society of Transplantation and Cellular Therapy (ASTCT) Consensus Grading for Cytokine Release Syndrome.
Time frame: Up to approximately 8 years
Arms E and J Only: Incidence and Severity of Cytokine-release Syndrome (CRS) Following Tocilizumab Premedication Followed by Treatment with Cevostamab
Cytokine release syndrome was recorded as an AE that generally occurs \>30 minutes after the start of Cevostamab administration and at any time afterward in a given cycle.
Time frame: Up to approximately 8 years
Area Under the Concentration-Time Curve (AUC) of Cevostamab
Defined as the total exposure of study drug.
Time frame: Up to approximately 8 years
AUC of Tocilizumab
Defined as the total exposure of study drug.
Time frame: Up to approximately 8 years
Maximum Observed Serum Concentration (Cmax) of Cevostamab
Defined as the maximum observed serum concentration of study drug.
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City of Hope
Duarte, California, United States
University of Colorado Denver
Aurora, Colorado, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Memorial Sloan Kettering
New York, New York, United States
Mount Sinai Hospital
New York, New York, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Tennessee Oncology - Nashville
Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
...and 7 more locations
Time frame: Up to approximately 8 years
Cmax of Tocilizumab
Defined as the maximum observed serum concentration of study drug.
Time frame: Up to approximately 8 years
Minimum Observed Serum Concentration (Cmin) of Cevostamab
Defined as the minimum observed serum concentration of study drug.
Time frame: Up to approximately 8 years
Cmin of Tocilizumab
Defined as the minimum observed serum concentration of study drug.
Time frame: Up to approximately 8 years
Clearance (CL) of Cevostamab
Defined as the volume of plasma cleared of the drug per unit time.
Time frame: Up to approximately 8 years
CL of Tocilizumab
Defined as the volume of plasma cleared of the drug per unit time.
Time frame: Up to approximately 8 years
Volume of Distribution at Steady State (Vdss) of Cevostamab
Defined as the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces.
Time frame: Up to approximately 8 years
Vdss of Tocilizumab
Defined as the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces.
Time frame: Up to approximately 8 years
Serum Concentration of Cevostamab
Time frame: Up to approximately 8 years
Serum Concentration of Tocilizumab
Time frame: Up to approximately 8 years
Objective Response Rate (ORR)
ORR is defined as percentage of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) . sCR is defined as CR (as defined below), plus: Normal FLC ratio and absence of clonal cells in bone marrow (BM) by immunohistochemistry (kappa/lambda ratio \</=4:1 or \>/=1:2 for kappa and lambda participants, respectively after counting \>/=100 plasma cells). CR is defined as no evidence of initial monoclonal protein isotype(s) on immunofixation of the serum and urine, disappearance of any soft tissue plasmacytomas, and \</= 5% plasma cells in BM. VGPR is defined as Serum and urine M-protein detectable by immunofixation but not on electrophoresis; or \>/=90% reduction in serum M-protein plus urine M-protein level \<100 milligrams (mg)/24 hr. PR is defined as \>/= 50% reduction of serum M-protein and reduction in 24-hour urine M-protein by \>/= 90% or to \< 200 mg/24 hours.
Time frame: Up to approximately 8 years
Duration of Response
Time from first occurrence of ORR (defined previously) to disease progression (PD) or death from any cause. PD: increase of \>/=25% from lowest response value in one of the following: serum M-protein (absolute increase \>/=0.5 grams per deciliter (g/dL); serum M-protein increase \>/=1g/dL, if lowest M component was \>/=5g/dL; urine M-protein (absolute increase \>/=200 mg/24 hours); no measurable serum and urine M-protein levels: difference between involved and uninvolved free light chain (FLC) levels (absolute increase \>10 mg/dL); no measurable serum and urine M-protein levels and no measurable disease by FLC: BM plasma cell % irrespective of baseline status (absolute % \>/=10%); new lesion(s) \>/=50% increase from lowest point in sum of the products of diameters of \> 1 lesion, or \>/=50% increase in longest diameter of a previous lesion \>1 centimeter (cm) in short axis; \>/=50% increase in circulating plasma cells (minimum 200 cells per microliter) if only measure of disease.
Time frame: Up to approximately 8 years
Change from Baseline in the Presence Anti-Drug Antibodies (ADAs)
To evaluate the immune response to the study drug.
Time frame: Up to approximately 8 years