For Healthcare Professionals

A Study Evaluating the Safety, Pharmacokinetics, and Activity of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma

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About the study

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.
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Who can take part

You may be eligible to participate in the study if you meet the following criteria:

INCLUSION CRITERIA

Inclusion Criteria:

  1. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  2. Life expectancy of at least 12 weeks
  3. Agreement to provide bone marrow biopsy and aspirate samples
  4. Resolution of adverse events from prior anti-cancer therapy to Grade <=1
  5. Measurable disease
  6. 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
  7. * For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm, during the treatment period, and for at least 2 months after the last dose of tocilizumab was administered to avoid exposing the embryo and sexual partner Additional Arm A-Specific Inclusion Criteria

    * Diagnosis of R/R MM for which no established therapy for MM is appropriate and available, or intolerance to those established therapies Additional Arm B-Specific Inclusion Criteria

  8. For Cohort B1S: Participants with R/R MM who have received at least two prior lines of treatment
  9. For Cohort B2S and additional cohorts: Participants with R/R MM who have received at least 1 prior line of treatment
  10. Agreement to comply with all requirements of the pomalidomide pregnancy prevention program
  11. 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
  12. * For men: agreement to remain abstinent or use a condom during the treatment period and for at least 4 weeks after the last dose of pomalidomide, (even if he has undergone a successful vasectomy) and agreement to refrain from donating sperm and blood during this same period Additional Arm C-Specific Inclusion Criteria

  13. For Cohort C1S: Participants with R/R MM who have received at least two prior lines of treatment
  14. For Cohort C2S and additional cohorts: Participants with R/R MM who have received at least 1 prior line of therapy
  15. 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
  16. 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

Exclusion Criteria:

  1. Prior treatment with cevostamab or another agent targeting FcRH5
  2. Inability to comply with protocol-mandated hospitalization and activities restrictions
  3. 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).
  4. 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
  5. 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
  6. Prior treatment with chimeric antigen receptor T (CAR T)-cell therapy within 12 weeks before first study treatment
  7. Treatment with radiotherapy within 4 weeks (systemic radiation) or 14 days (focal radiation) prior to first study treatment
  8. 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
  9. Autologous SCT within 100 days prior to first study treatment
  10. Prior allogeneic stem cell transplant(ation) (SCT)
  11. Circulating plasma cell count exceeding 500/micro L or 5% of the peripheral blood white cells
  12. Prior solid organ transplantation
  13. History of autoimmune disease
  14. History of confirmed progressive multifocal leukoencephalopathy
  15. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
  16. Known history of amyloidosis
  17. Lesions in proximity of vital organs that may develop sudden decompensation/deterioration in the setting of a tumor flare
  18. History of other malignancy within 2 years prior to screening
  19. Known treatment-related, immune-mediated adverse events associated with prior checkpoint inhibitors
  20. Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, neurodegenerative disease, or CNS involvement by MM
  21. Significant cardiovascular disease
  22. Symptomatic active pulmonary disease or requiring supplemental oxygen
  23. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
  24. Known or suspected chronic active Epstein-Barr virus (EBV) infection
  25. Recent major surgery within 4 weeks prior to first study treatment
  26. Positive serologic or PCR test results for acute or chronic hepatitis B virus (HBV) infection
  27. Acute or chronic hepatitis C virus (HCV) infection
  28. Known history of Grade >= 3 CRS or immune effector cell-associated neurotoxicity syndrome (ICANS) with prior bispecific therapies
  29. Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
  30. 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
  31. Positive and quantifiable EBV polymerase chain reaction (PCR) or Cytomegalovirus (CMV) PCR prior to first study treatment
  32. Known history of HIV seropositivity
  33. 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
  34. 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
  35. * History of illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment Additional Arm B-Specific Exclusion Criteria

  36. 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
  37. 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)
  38. History of erythema multiforme, Grade >=3 rash, blistering, or severe hypersensitivity to prior treatment with immunomodulatory drugs such as thalidomide, lenalidomide, or pomalidomide
  39. Inability to tolerate thromboprophylaxis, or contraindication to thromboprophylaxis
  40. * GI disease that might significantly alter absorption of oral drugs Additional Arm C-Specific Exclusion Criteria

  41. Pregnant or breastfeeding, or intending to become pregnant during the study or within 102 days after the last dose of daratumumab
  42. Known hypersensitivity to biopharmaceuticals produced in CHO cells or any component of daratumumab formulations
  43. Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal
  44. Known moderate or severe persistent asthma within the past 2 years, or current uncontrolled asthma of any classification
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Study Locations

Enter your ZIP code/Postal code/PIN code to locate study sites near you:

How to Apply


Contact the study center to learn if this study is a good match for you.
Phone iconCall 888-662-6728 (U.S. and Canada)Email iconEmail Study Center

Study Details


Contition

Multiple Myeloma

Age

18+

Phase

PHASE1

Participants Needed

184

Est. Completion Date

Jul 15, 2025

Treatment Type

INTERVENTIONAL


Sponsor

Genentech, Inc.

ClinicalTrials.gov NCT Identifier

NCT04910568

Study Number

GO42552

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