A Study Evaluating the Safety, Pharmacokinetics, and Activity of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma
NCT ID: NCT04910568
Last Updated: 2025-12-24
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
ACTIVE_NOT_RECRUITING
PHASE1
126 participants
INTERVENTIONAL
2021-07-26
2029-12-10
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Single-Agent Cevostamab (Arm A)
Cohort A1S is a safety run-in arm evaluating cevostamab administered in 28-day cycles on a modified weekly schedule.
Cohort A1E, an expansion cohort, has been opened and finished enrolling participants. Participants will be treated with single-agent cevostamab administered in 28-day cycles on a modified weekly schedule.
Cevostamab
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 after Cycle 13. For Arms B and C, participants can be treated until disease progression or unacceptable toxicity.
Tocilizumab
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.
Dexamethasone
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.
Cevostamab plus Pomalidomide and Dexamethasone (Pd) (Arm B)
Participants will be treated with cevostamab monotherapy during a 14-day period prior to the start of pomalidomide treatment (cevostamab pre-phase).
Cohort B1S is a safety run-in arm evaluating cevostamab and Pd administered in 28-day cycles every 2 weeks (Q2W) followed by every 4 weeks (Q4W) schedule. Additional safety run-in cohort(s) with lower target dose levels of cevostamab may be opened prior to opening the expansion cohorts.
Two target dose levels of target dose level 1 (DL1) and lower dose level -1 (DL-1) of cevostamab will be selected for randomization in expansion cohorts. Expansion cohorts will follow the same Q2W/Q4W dosing schedule as Cohort B1S.
Cevostamab
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 after Cycle 13. For Arms B and C, participants can be treated until disease progression or unacceptable toxicity.
Tocilizumab
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.
Pomalidomide
Pomalidomide will be administered orally (PO) on a 28-day cycle.
Dexamethasone
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.
Cevostamab plus Daratumumab and Dexamethasone (Dd) (Arm C)
Cohort C1S is a safety run-in arm evaluating cevostamab and Dd administered in 21 day cycles from Cycle(C)1 - C8 every 3 weeks (Q3W) and 28-day cycles from C9 onwards Q4W. Additional safety run-in cohort(s) with lower target dose levels of cevostamab may be opened prior to opening the expansion cohorts.
Two target dose levels of DL1 and DL-1 of cevostamab will be selected for randomization in expansion cohorts. Expansion cohorts will follow the same Q3W/Q4W dosing schedule as Cohort C1S.
Cevostamab
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 after Cycle 13. For Arms B and C, participants can be treated until disease progression or unacceptable toxicity.
Tocilizumab
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.
Daratumumab
Daratumumab will be administered subcutaneously (SC) on 21 day (C1-8) and 28-day cycles (C9 onwards).
Dexamethasone
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.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Cevostamab
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 after Cycle 13. For Arms B and C, participants can be treated until disease progression or unacceptable toxicity.
Tocilizumab
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.
Pomalidomide
Pomalidomide will be administered orally (PO) on a 28-day cycle.
Daratumumab
Daratumumab will be administered subcutaneously (SC) on 21 day (C1-8) and 28-day cycles (C9 onwards).
Dexamethasone
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.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Life expectancy of at least 12 weeks
* Agreement to provide bone marrow biopsy and aspirate samples
* Resolution of adverse events from prior anti-cancer therapy to Grade \<=1
* Measurable disease
* For women of childbearing potential: agreement to remain abstinent or use contraception, during the treatment period (including treatment interruptions) and for at least 5 months after the last dose of cevostamab and at least 3 months after the last dose of tocilizumab was administered
* For Cohort B1S: Participants with R/R MM who have received at least two prior lines of treatment
* For Cohort B2S and additional cohorts: Participants with R/R MM who have received at least 1 prior line of treatment
* Agreement to comply with all requirements of the pomalidomide pregnancy prevention program
* For women of childbearing potential: agreement to remain abstinent or use two reliable methods of contraception starting at least 4 weeks prior to, during the treatment period, and for at least 4 weeks after the last dose of pomalidomide was administered
* For Cohort C1S: Participants with R/R MM who have received at least two prior lines of treatment
* For Cohort C2S and additional cohorts: Participants with R/R MM who have received at least 1 prior line of therapy
* For women of childbearing potential: agreement to remain abstinent or use contraceptive methods during the treatment period and for at least 102 days after the last dose of daratumumab was administered
* For men: agreement to remain abstinent or use a condom during the treatment period and for at least 102 days after the last dose of daratumumab was administered to avoid exposing the embryo, and agreement to refrain from donating sperm during this same period
Exclusion Criteria
* Inability to comply with protocol-mandated hospitalization and activities restrictions
* Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the last dose of cevostamab or within 3 months after the last dose of tocilizumab (if applicable).
* Prior use of any monoclonal antibody, radioimmunoconjugate, or antibody-drugconjugate as anti-cancer therapy within 4 weeks before first study treatment, except for the use of non-myeloma therapy
* Prior treatment with systemic immunotherapeutic agents, including, but not limited to, cytokine therapy and anti-CTLA4, anti-PD-1, and antiPD-L1 therapeutic antibodies within 12 weeks or 5 half-lives of the drug, whichever is shorter, before first study treatment
* Prior treatment with chimeric antigen receptor T (CAR T)-cell therapy within 12 weeks before first study treatment
* Treatment with radiotherapy within 4 weeks (systemic radiation) or 14 days (focal radiation) prior to first study treatment
* Treatment with any chemotherapeutic agent or other anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to first study treatment
* Autologous SCT within 100 days prior to first study treatment
* Prior allogeneic stem cell transplant(ation) (SCT)
* Circulating plasma cell count exceeding 500/micro L or 5% of the peripheral blood white cells
* Prior solid organ transplantation
* History of autoimmune disease
* History of confirmed progressive multifocal leukoencephalopathy
* History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
* Known history of amyloidosis
* Lesions in proximity of vital organs that may develop sudden decompensation/deterioration in the setting of a tumor flare
* History of other malignancy within 2 years prior to screening
* Known treatment-related, immune-mediated adverse events associated with prior checkpoint inhibitors
* Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, neurodegenerative disease, or CNS involvement by MM
* Significant cardiovascular disease
* Symptomatic active pulmonary disease or requiring supplemental oxygen
* Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
* Known or suspected chronic active Epstein-Barr virus (EBV) infection
* Recent major surgery within 4 weeks prior to first study treatment
* Positive serologic or PCR test results for acute or chronic hepatitis B virus (HBV) infection
* Acute or chronic hepatitis C virus (HCV) infection
* Known history of Grade \>= 3 CRS or immune effector cell-associated neurotoxicity syndrome (ICANS) with prior bispecific therapies
* Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
* Active symptomatic coronavirus disease 2019 (COVID-19) infection at study enrollment or requiring treatment with intravenous (IV) antiviral where the last dose of IV antiviral treatment was given within 14 days prior to first study treatment. Patients with active COVID-19 infection must have clinical recovery and two negative antigen tests at least 24 hours apart prior to first study treatment
* Positive and quantifiable EBV polymerase chain reaction (PCR) or Cytomegalovirus (CMV) PCR prior to first study treatment
* Known history of HIV seropositivity
* Administration of a live, attenuated vaccine within 4 weeks before first study treatment or anticipation that such a live attenuated vaccine will be required during the study
* Treatment with systemic immunosuppressive medications, with the exception of corticosteroid treatment \<=10 mg/day prednisone or equivalent, within 2 weeks prior to first study treatment
* Pregnant or breastfeeding, or intending to become pregnant 4 weeks prior to initiation of study treatment, during the study, (including treatment interruptions) or within 4 weeks after the last dose of pomalidomide
* Significant cardiovascular disease (such as, but not limited to, New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 12 months, uncontrolled arrhythmias, or unstable angina)
* History of erythema multiforme, Grade \>=3 rash, blistering, or severe hypersensitivity to prior treatment with immunomodulatory drugs such as thalidomide, lenalidomide, or pomalidomide
* Inability to tolerate thromboprophylaxis, or contraindication to thromboprophylaxis
* Pregnant or breastfeeding, or intending to become pregnant during the study or within 102 days after the last dose of daratumumab
* Known hypersensitivity to biopharmaceuticals produced in CHO cells or any component of daratumumab formulations
* Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) \<50% of predicted normal
* Known moderate or severe persistent asthma within the past 2 years, or current uncontrolled asthma of any classification
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Hoffmann-La Roche
INDUSTRY
Genentech, Inc.
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Clinical Trials
Role: STUDY_DIRECTOR
Genentech, Inc.
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
City of Hope
Duarte, California, United States
City of Hope - Lennar Foundation Cancer Center
Irvine, California, United States
Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center
Denver, Colorado, United States
Karmanos Cancer Institute.
Detroit, Michigan, United States
Washington University School of Medicine
St Louis, Missouri, United States
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia
The Alfred Hospital
Melbourne, Victoria, Australia
Cross Cancer Institute
Edmonton, Alberta, Canada
Hamilton Health Sciences
Hamilton, Ontario, Canada
University Health Network
Toronto, Ontario, Canada
Fakultni Nemocnice Ostrava
Ostrava, , Czechia
Rigshospitalet
København Ø, , Denmark
Hôpital Saint-Louis
Paris, , France
CHU de Poitiers - La Miletrie
Poitiers, , France
Rambam Medical Center
Haifa, , Israel
Asst Papa Giovanni Xxiii
Bergamo, Lombardy, Italy
A.O. Spedali Civili Di Brescia-P.O. Spedali Civili
Brescia, Lombardy, Italy
Yamagata University Hospital
Yamagata, , Japan
Uniwersyteckie Centrum Kliniczne
Gda?sk, , Poland
Pratia Onkologia Katowice
Katowice, , Poland
Uniwersytecki Szpital Kliniczny w Poznaniu
Późna, , Poland
Seoul National University Hospital
Seoul, , South Korea
Samsung Medical Center
Seoul, , South Korea
Hospital Universitari Vall d'Hebron
Barcelona, , Spain
Hospital General Universitario Gregorio Marañon
Madrid, , Spain
University College London Hospitals NHS Foundation Trust
London, , United Kingdom
Royal Marsden Hospital
Sutton, , United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2021-000238-33
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
GO42552
Identifier Type: -
Identifier Source: org_study_id