Badanie mające na celu ocenę bezpieczeństwa stosowania, farmakokinetyki i działania cewostamabu w monoterapii oraz cewostamabu w skojarzeniu z pomalidomidem i deksametazonem lub cewostamabu w skojarzeniu z daratumumabem i deksametazonem u pacjentów z nawrotowym lub opornym na leczenie szpiczakiem mnogim (CAMMA 1).

Kryteria wyłączenia kto nie może wziąć udziału (44)

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 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 immune effector cell associated hemophagocytic lymphohistiocytosis like syndrome (IEC HS)
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