Multiple myeloma Cancer Multiple myeloma
Conditions
Interventions
Current interventions as of 09/06/2025:
Arm A: Dose-escalation cohorts:
Participants will receive cevostamab SC, with step-up dosing on Days 1 and 8 of Cycle 1 (the duration of each cycle is 28 days
Sponsors
Genentech Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age =18 years at time of signing Informed Consent Form 2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 3. Life expectancy of at least 12 weeks 4. Participants with a diagnosis of R/R MM for which no established therapy for multiple myeloma (MM) is appropriate and available, or intolerance to those established therapies 5. Agreement to provide bone marrow biopsy and aspirate samples 6. Adverse events from prior anti-cancer therapy resolved to Grade less than or equal to (=) 1, except any grade alopecia and peripheral sensory or motor neuropathy which must have resolved to Grade = 2 7. Measurable disease defined by laboratory test results
Exclusion criteria
Exclusion criteria: Current participant exclusion criteria as of 06/06/2024: 1. Prior treatment with cevostamab or another agent targeting fragment crystallizable receptor-like 5 (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-drug conjugate as anti-cancer therapy within 4 weeks prior to first study treatment, except for the use of non-myeloma therapy 5. Prior treatment with systemic checkpoint inhibitors, including, but not limited to anti-cytotoxic T-lymphocyte associated (CTLA4), anti-programmed death-1 (PD-1), and anti-programmed death-ligand 1 (PD-L1) therapeutic antibodies within 12 weeks or 5 half-lives of the drug, whichever is shorter, prior to first study treatment 6. Prior treatment with allogeneic or autologous chimeric antigen receptor (CAR) T-cell therapy within 12 weeks prior to first study treatment 7. Known treatment-related, immune-mediated adverse events associated with prior checkpoint inhibitors 8. Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) 9. 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 10. Treatment with radiotherapy within 4 weeks (systemic radiation) or 14 days (focal radiation) prior to first study treatment 11. Autologous stem cell transplant (SCT) within 100 days prior to first study treatment 12. Prior allogeneic SCT 13. Prior solid organ transplantation 14. Circulating plasma cell count exceeding 500/microlitres (µL) or 5% of the peripheral blood white cells 15. History of autoimmune disease 16. History of confirmed progressive multifocal leukoencephalopathy 17. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins) 18. Known history of amyloidosis (e.g., positive Congo Red stain or equivalent in tissue biopsy) 19. Participants with lesions in proximity of vital organs that may develop sudden decompensation/deterioration in the setting of a tumor flare 20. History of other malignancy within 2 years prior to screening, except those with negligible risk of metastasis or death 21. Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, neurodegenerative disease, or CNS involvement by MM 22. Significant cardiovascular disease that may limit a participant's ability to adequately respond to a CRS event 23. Symptomatic active pulmonary disease or requiring supplemental oxygen 24. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antimicrobials where the last dose of IV antimicrobial was given within 14 days prior to first study treatment 25. Active symptomatic COVID-19 infection at study enrollment or requiring treatment with 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 a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 09/06/2025: 1. Percentage of participants with adverse events (AEs) from screening up to 90 days after the end of treatment (up to approximately 4 years 1 month) 2. Percentage of participants with severity of AEs determined according to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) and American Society of Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS from screening up to 90 days after the end of treatment (up to approximately 4 years 1 month) 3. Recommended Phase II Dose (RP2D) of SC cevostamab that is safe and tolerable and measured using DLT in cycle 1 (up to 28 days) _____ Previous primary outcome measure as of 20/02/2024: 1. Percentage of participants with adverse events (AEs) from screening up to 90 days after the end of treatment (up to approximately 4 years 1 month) 2. Percentage of participants with severity of adverse events determined according to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) and American Society of Transplantation and Cellular Therapy (ASTCT) Consensus Grading for Cytokine Release Syndrome (CRS) from screening up to 90 days after the end of treatment (up to approximately 4 years 1 month) 3. Recommended Phase II Dose (RP2D) of SC cevostamab that is safe and tolerable and measured using Dose Limiting Toxicity (DLT) in cycle 1 (28 days) _____ Previous primary outcome measure: 1. Percentage of participants with adverse events (AEs) from screening up to 30 days after the end of treatment (up to approximately 2 years) 2. Percentage of participants with severity of adverse events determined according to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) and American Society of Transplantation and Cellular Therapy (ASTCT) Consensus Grading for Cytokine Release Syndrome (CRS) from screening up to 30 days after the end | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 09/09/2025: 1. Objective response rate (ORR) is defined as the percentage of participants with a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) on two consecutive occasions as determined by the investigator according to International Myeloma Working Group (IMWG) Uniform Response Criteria measured from baseline up to end of treatment (up to approximately 4 years 1 month) 2. Percentage of participants with CR/sCR from baseline up to end of treatment (up to approximately 4 years 1 month) 3. Percentage of participants with VGPR from baseline up to end of treatment (up to approximately 4 years 1 month) 4. Progression-free survival (PFS) as determined by the investigator according to IMWG Uniform Response Criteria from the time of enrollment to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 4 years 1 month) 5. Duration of response (DOR) as determined by the investigator according to IMWG Uniform Response Criteria measured from the date of first documented response of PR or better until date of disease progression or death from any cause (up to approximately 4 years 1 month) 6. Time to first response as determined by the investigator according to IMWG Uniform Response Criteria measured from the time of initiation of study treatment to achieving a confirmed PR or better (up to approximately 4 years 1 month) 7. Time to best response as determined by the investigator according to IMWG Uniform Response Criteria measured from the time of initiation of study treatment to achieving the deepest response (up to approximately 4 years 1 month) 8. Overall survival (OS) as determined by the investigator according to IMWG Uniform Response Criteria measured from the time of initiation of study treatment to death from any cause (up to approximately 4 years 1 month) 9. Serum concentration of cevostamab measured us | — |
Countries
Australia, Belgium, Greece, Italy, Korea, South
Contacts
Public ContactClinical Trials
Outcome results
None listed