This Phase Ib, multicenter, open-label study will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cevostamab monotherapy, cevostamab plus pomalidomide and dexamethasone (Pd) or cevostamab plus daratumumab and dexamethasone (Dd) which will be administered to participants with relapsed or refractory multiple myeloma (R/R MM) via intravenous (IV) infusion.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
186
Cevostamab will be administered intravenously on a 28-day cycle, up to a total of 13 cycles (Arm A), in 28-day cycles Q2W followed by Q4W (Arm B) and in 21 day cycles from C1-C8 Q3W and 28-day cycles from C9 onwards Q4W (Arm C). For Arm A, participants have the option to enter re-treatment within 12 months of the end of treatment visit. For Arms B and C, participants can be treated until disease progression or unacceptable toxicity.
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.
Pomalidomide will be administered orally (PO) on a 28-day cycle.
Recommended Phase II Dose (RP2D)
Time frame: Baseline up to approximately 4 years
Percentage of Participants with Adverse Events
Time frame: Baseline up to approximately 4 years
Percentage of Dose Interruptions
Time frame: Baseline up to approximately 4 years
Percentage of Dose Reductions
Time frame: Baseline up to approximately 4 years
Percentage of Dose Intensity
Time frame: Baseline up to approximately 4 years
Percentage of Treatment Discontinuation
Time frame: Baseline up to approximately 4 years
Objective Response Rate (ORR)
Time frame: Baseline up to approximately 4 years
Complete Response/Stringent Complete Response (CR/sCR) Rate
Time frame: Baseline up to approximately 4 years
Rate of Very Good Partial Response (VGPR) or Better
Time frame: Baseline up to approximately 4 years
Progression-free Survival (PFS)
Time frame: Start of study treatment to first date of disease progression or death from any cause, whichever occurs first (up to approximately 4 years)
Duration of Response (DOR)
Reference Study ID Number: GO42552 https://forpatients.roche.com/No attachments to email below.
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Daratumumab will be administered subcutaneously (SC) on 21 day (C1-8) and 28-day cycles (C9 onwards).
Arm A: Dexamethasone will be administered as a premedication. Arms B and C: Dexamethasone will be administered via IV or orally at 20 mg as study investigational medicinal product.
City of Hope
Duarte, California, United States
ACTIVE_NOT_RECRUITINGCity of Hope - Lennar Foundation Cancer Center
Irvine, California, United States
ACTIVE_NOT_RECRUITINGColorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center
Denver, Colorado, United States
RECRUITINGWinship Cancer Institute
Atlanta, Georgia, United States
WITHDRAWNKarmanos Cancer Institute.
Detroit, Michigan, United States
COMPLETEDWashington University School of Medicine
St Louis, Missouri, United States
ACTIVE_NOT_RECRUITINGPeter MacCallum Cancer Centre
Melbourne, Victoria, Australia
ACTIVE_NOT_RECRUITINGThe Alfred Hospital
Melbourne, Victoria, Australia
RECRUITINGCross Cancer Institute
Edmonton, Alberta, Canada
ACTIVE_NOT_RECRUITINGHamilton Health Sciences
Hamilton, Ontario, Canada
ACTIVE_NOT_RECRUITING...and 24 more locations
Time frame: From first partial response (PR) or better until the first date of disease progression or death from any cause, whichever occurs first (up to approximately 4 years)
Time to First Response (for Participants who Achieve a Response of Partial Response (PR) or Better)
Time frame: Baseline up to approximately 4 years
Time to Best Response (for Participants who Achieve a Response of PR or Better)
Time frame: Baseline up to approximately 4 years
Overall Survival (OS)
Time frame: Baseline up until death from any cause (up to approximately 4 years)
Serum Concentration of Cevostamab at Specified Timepoints
Time frame: Cevostamab Pre-Phase (CPP) Day (D) 1 up to approximately 3 years
Total Exposure (Area Under the Concentration-time Curve [AUC]) of Cevostamab
Time frame: CPP D1 up to approximately 4 years
Maximum Observed Serum Concentration (Cmax) of Cevostamab
Time frame: CPP D1 up to approximately 4 years
Minimum Observed Serum Concentration (Cmin) of Cevostamab
Time frame: CPP D1 up to approximately 4 years
Clearance of Cevostamab
Time frame: CPP D1 up to approximately 4 years
Volume of Distribution at Steady State of Cevostamab
Time frame: CPP D1 up to approximately 4 years
Number of Anti-drug Antibody (ADAs) Against Cevostamab at Baseline
Time frame: Baseline
Percentage of Participants with ADAs Against Cevostamab During the Study
Time frame: Up to approximately 4 years
Serum Concentration of Pomalidomide
Time frame: From Cycle 1 Day 1 through Cycle 6 Day 15. Each cycle=28 days
Serum Concentration of Daratumumab
Time frame: From C1D1 until disease progression or unexpected toxicity. Cycles 1-8 are 21 days and Cycle 9 onward are 28 days.