Study of Lenalidomide and Dexamethasone With or Without Pembrolizumab (MK-3475) in Participants With Newly Diagnosed Treatment Naive Multiple Myeloma (MK-3475-185/KEYNOTE-185)
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Pembrolizumab; Lenalidomide; Dexamethasone
Intervention description: IV infusion; oral capsules; oral tablets
Intervention MeSH terms: Dexamethasone; Pembrolizumab; Lenalidomide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 310.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: PD1; PD-1; PD-L1; PDL1

Summary:

      The purpose of this study is to compare the efficacy of lenalidomide and low dose
      dexamethasone with pembrolizumab (MK-3475) to that of lenalidomide and low dose dexamethasone
      without pembrolizumab in terms of progression-free survival (PFS) in participants with newly
      diagnosed and treatment-naïve multiple myeloma who are ineligible for autologous stem cell
      transplant (Auto-SCT). The study's primary hypothesis is that pembrolizumab in dexamethasone
      prolongs progression free survival (PFS) as assessed by Clinical Adjudication Committee (CAC)
      blinded central review using International Myeloma Working Group (IMWG) response criteria
      compared to treatment combination with lenalidomide and low-dose with lenalidomide and
      low-dose dexamethasone (standard of care, SOC) alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Confirmed diagnosis of active multiple myeloma and measurable disease.

          -  Ineligible to receive treatment with auto-SCT due to age (≥65 years old) or any
             significant coexisting medical condition (cardiac, renal, pulmonary or hepatic
             dysfunction), likely to have a negative impact on tolerability of auto-SCT.
             Participants <65 years of age who refuse auto-SCT are not eligible for this study.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

          -  Female participants of childbearing potential must have 2 negative urine pregnancy
             tests (with a sensitivity of at least 25 Milli-international units/milliliter) within
             10 to 14 days and within 24 hours prior to receiving study medication.

          -  Female participants of childbearing potential must agree to use adequate contraception
             28 days prior to study start, continuing throughout the study, and for up to 28 days
             after the last dose of lenalidomide (or 120 days after the last dose of
             pembrolizumab).

          -  Male participants of childbearing potential must agree to use adequate contraception
             from the first dose of study medication, continuing throughout the study, and for up
             to 28 days after the last dose of lenalidomide (or 120 days after the last dose of
             pembrolizumab).

        Exclusion Criteria:

          -  Has undergone prior allogeneic hematopoietic stem cell transplantation within the last
             5 years.

          -  Has peripheral neuropathy ≥ Grade 2.

          -  Has a known additional malignancy that is progressing or requires active treatment
             within the last 5 years (except for basal cell carcinoma of the skin, squamous cell
             carcinoma of the skin, or in situ cervical cancer that has undergone potentially
             curative therapy).

          -  Has history of non-infectious pneumonitis that required steroids or current
             pneumonitis

          -  Has received prior therapy with an anti-programmed cell death 1 receptor (anti-PD-1),
             anti-programmed death-ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137, or anti-cytotoxic
             T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other
             antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).

          -  Has a known Human Immunodeficiency Virus (HIV), or a known, active Hepatitis B (HBV),
             or a known, active Hepatitis C (HCV) infection.

          -  Is unable or unwilling to undergo thromboembolic prophylaxis including, as clinically
             indicated, aspirin, Coumadin (warfarin) or low-molecular weight heparin.

          -  Has lactose intolerance.

          -  Has an invasive fungal infection.