Trattamento

Experimental: Part 1 Safety Lead-In Dose Escalation: Elranatamab + Daratumumab

Experimental: Part 2 Randomized Arm A: Elranatamab

Experimental: Part 2 Randomized Arm B: Elranatamab + Daratumumab

Active Comparator: Part 2 Randomized Arm C: Daratumumab + Pomalidomide + Dexamethasone

Obiettivo primario

1. Part 1 Safety Lead-In: Incidence of dose limiting toxicities [ Time Frame: First 42 days after first elranatamab dose ]
2. Part 2 Randomized: Progression free survival per International Myeloma Working Group criteria [ Time Frame: From date of randomization to date of progressive disease, discontinuation from the study, death, or censoring, whichever occurs first, assessed up to 32 month.

Criteri di inclusione

• Prior diagnosis of multiple myeloma as defined by IMWG criteria (Rajkumar et al, 2014).
• Measurable disease based on IMWG criteria as defined by at least 1 of the following:
  • Serum M-protein ≥0.5 g/dL.
  • Urinary M-protein excretion ≥200 mg/24 hours.
  • Serum immunoglobulin FLC ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio (<0.26 or >1.65).
• Prior anti-multiple myeloma therapy including treatment with lenalidomide and a proteasome inhibitor.
• ECOG performance status ≤2.
• Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1.
• Not pregnant and willing to use contraception.

Criteri di esclusione

• Smoldering multiple myeloma.
• Plasma cell leukemia.
• Amyloidosis.
• POEMS Syndrome.
• Stem cell transplant within 12 weeks prior to enrolment, or active graft versus host disease.
• Active HBV, HCV, SARS-CoV2, HIV, or any active, uncontrolled bacterial, fungal, or viral infection.
• Any other active malignancy within 3 years prior to enrolment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
• Previous treatment with a BCMA-directed therapy.
• Anti-CD38-directed therapy within 6 months preceding the first dose of treatment in this study.
• Live attenuated vaccine within 4 weeks of the first dose of study intervention.
• Administration with an investigational product (e.g. drug or vaccine) concurrent with study intervention or within 30 days preceding the first dose of study intervention used in this study.