Study of Pomalidomide and Low Dose Dexamethasone With or Without Pembrolizumab (MK-3475) in Refractory or Relapsed and Refractory Multiple Myeloma (rrMM) (MK-3475-183/KEYNOTE-183)
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Pembrolizumab; Pomalidomide; Dexamethasone
Intervention description: pembrolizumab 200 mg IV infusion; pomalidomide 4 mg capsules; dexamethasone 40 mg tablets
Intervention MeSH terms: Dexamethasone; Pembrolizumab; Pomalidomide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 251.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: PDL1; PD1; Multiple Myeloma

Summary:

      The purpose of this study is to compare the efficacy of pomalidomide and low dose
      dexamethasone with pembrolizumab (MK-3475) to that of pomalidomide and low dose dexamethasone
      without pembrolizumab in terms of Progression-Free Survival (PFS) in participants with
      refractory or relapsed and refractory multiple myeloma (rrMM) who have undergone at least 2
      lines of prior treatment. The study's 2 primary hypotheses are: 1. Pembrolizumab in
      combination with pomalidomide and low dose dexamethasone prolongs PFS as assessed by Clinical
      Adjudication Committee (CAC) blinded central review using International Myeloma Working Group
      Criteria for Response Assessment in Multiple Myeloma (IMWG) criteria compared to treatment
      with pomalidomide and low dose dexamethasone standard of care (SOC) alone. 2. Pembrolizumab
      in combination with pomalidomide and low dose dexamethasone prolongs OS compared to treatment
      with pomalidomide and low dose dexamethasone (SOC) alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has a confirmed diagnosis of active multiple myeloma and measurable disease

          -  Must have undergone prior treatment with ≥2 treatment lines of anti-myeloma therapy
             and must have failed last line of treatment (refractory to last line of treatment)

          -  Prior anti-myeloma treatments must have included an immunomodulatory drug (IMiD) AND
             proteasome inhibitor alone or in combination and participant must have failed therapy
             with an IMiD OR proteasome inhibitor

          -  Has performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale

          -  Female participants of childbearing potential must have 2 negative urine human
             chorionic gonadotropin tests within 10 to 14 days and within 24 hours prior to
             receiving study medication

          -  Female participants of childbearing potential and male participants must agree to use
             adequate contraception 28 days prior to study start and continuing for up to 28 days
             after the last dose of pomalidomide (or 120 days after the last dose of pembrolizumab)

        Exclusion Criteria:

          -  Has had prior anti-myeloma therapy within 2 weeks prior to study start and has not
             recovered (i.e., ≤ Grade 1 or at Baseline) from adverse events due to a previously
             administered agent

          -  Has undergone prior allogeneic hematopoietic stem cell transplantation within the last
             5 years. (Participants who have had a transplant greater than 5 years ago are eligible
             as long as there are no symptoms of Graft versus Host Disease [GVHD]).

          -  Has received autologous stem cell transplant (auto-SCT) within 12 weeks before the
             first infusion or is planning for or is eligible for auto-SCT

          -  Has received previous therapy with pomalidomide

          -  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 a 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),
             antiprogrammed 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 costimulation or checkpoint pathways)

          -  Is pregnant or breast-feeding