A Study to Examine the Effects of Novel Therapy Linvoseltamab in Combination With Other Cancer Treatments for Adult Patients With Multiple Myeloma That is Resistant to Current Standard of Care Treatments
Multiple Myeloma
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Relapsed/Refractory Multiple Myeloma (RRMM), B-cell maturation antigen (BCMA), Anti-CD3 monoclonal antibodies (mAbs)
Eligibility Criteria
Key Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1
Relapsed/refractory multiple myeloma (MM): Progression of disease following at least 3 lines of therapy, or least 2 lines of therapy and either:
- prior exposure to at least 1 anti-CD38 antibody, 1 IMiD and 1 PI or
- double-refractory to 1 PI and 1 IMiD, or the combination of 1 PI and 1 IMiD. Cohort 1: Prior treatment with daratumumab is allowed if previously tolerated. However, patients cannot be refractory to an anti-CD38 antibody-containing regimen. In addition, patients must have a 6-month washout from prior anti-CD38 antibody therapy.
Cohort 2: Prior treatment with carfilzomib is allowed if previously tolerated at the approved full dose. However, patients cannot be refractory to a carfilzomib-containing regimen. In addition, patients must have a 6-month washout from prior carfilzomib therapy.
Cohort 3: Prior treatment with lenalidomide is allowed if previously tolerated at the approved full dose. However, a patient cannot be refractory to any combination regimen that included 25 mg of lenalidomide. In addition, patients must have a 6-month washout from prior lenalidomide therapy (including maintenance therapy).
Cohort 4: Prior treatment with bortezomib is allowed if previously tolerated at the approved full dose. However, a patient cannot be refractory to any combination regimen including the approved induction dose of bortezomib. In addition, patients must have a 6-month washout from prior bortezomib therapy.
- Participants must have measurable disease and as defined in the protocol for response assessment as per the 2016 International Myeloma Working Group (IMWG) response assessment criteria
- Adequate creatinine clearance, hematologic and hepatic functions, as defined in protocol
- Life expectancy of at least 6 months
Key Exclusion Criteria:
- Diagnosis of plasma cell leukemia, primary light-chain amyloidosis (excluding myeloma associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Participants with known MM brain lesions or meningeal involvement
- Treatment with any systemic anti-myeloma therapy within 5 half-lives or within 21 days prior to first administration of study drug regimen, whichever is shorter.
- History of allogeneic stem cell transplantation, or autologous stem cell transplantation within 12 weeks of the start of study drug regimen
- For participants with peripheral neuropathy grade ≥2 receiving bortezomib-based treatment (cohort 4 only)
- Prior treatment with BCMA-directed immunotherapies, including any chimeric antigen receptor T cell (CAR T) therapy (Note: BCMA antibody-drug conjugates are not excluded)
- History of neurodegenerative condition or central nervous system (CNS) movement disorder or participants with a history of seizure within 12 months prior to study enrollment are excluded
- Live or attenuated vaccination within 28 days prior to first study drug regimen administration with a vector that has replicative potential
- Cardiac ejection fraction <40% by echocardiogram (Echo) or multigated acquisition (MUGA) scan.
- Pregnant or breasting feeding women or women of childbearing potential (WOCBP) with positive pregnancy test result
- WOCBP or men who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose.
NOTE: Other protocol defined inclusion/exclusion criteria apply
Sites / Locations
- Ohio State UniversityRecruiting
- Chu De LilleRecruiting
- CHU de MontpellierRecruiting
- AP-HP Hôpital Necker - Enfants MaladesRecruiting
- CHU de PoitiersRecruiting
- General Hospital of Athens Alexandra - Department of Clinical TherapeuticsRecruiting
- General Hospital of Athens AlexandraRecruiting
- Hospital Universitario Marqués de Valdecilla (HUMV)Recruiting
- Clinica Universidad de NavarraRecruiting
- Hospital Universitario Germans Trias i PujolRecruiting
- Institut Clinic de Nefrologia i Urologia - ICNU, Hospital Clinic i Provincial de BarcelonaRecruiting
- Hospital universitiario de La PrinceaRecruiting
- Clinica Universidad de NavarraRecruiting
- Hospital Ramon Y CajalRecruiting
- Hospital Universitario HM SanchinarroRecruiting
- Hospital Universitario Quiron Salud MadridRecruiting
- Hospital Universitario de SalamancaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Cohort 1: Linvoseltamab + Daratumumab
Cohort 2: Linvolseltamab + Carfilzomib
Cohort 3: Linvoseltamab + Lenalidomide
Cohort 4: Linvoseltamab + Bortezomib
Cohort 5: Linvoseltamab + Pomalidomide
Cohort 6: Linvoseltamab + Isatuximab
Cohort 7: Linvoseltamab + Fianlimab
Cohort 8: Linvoseltamab + Cemiplimab
Cohort 9: Linvoseltamab + Nirogacestat
Linvoseltamab + Daratumumab
Linvoseltamab + Carfilzomib
Linvoseltamab + Lenalidomide
Linvoseltamab + Bortezomib
Linvoseltamab + Pomalidomide
Linvoseltamab + Isatuximab
Linvoseltamab + Fianlimab
Linvoseltamab + Cemiplimab
Linvoseltamab + Nirogacestat