Avelumab In Patients With Previously Treated Advanced Stage Classical Hodgkin's Lymphoma (JAVELIN HODGKINS)

• Drug: Avelumab
  Anti-PD-L1 antibody at X1 mg IV every 2 weeks to optimize dosing for expansion. Treatment with avelumab will continue until disease progression.
• Drug: Avelumab
  Anti-PD-L1 antibody at X2 mg IV every 2 weeks to optimize dosing for expansion. Treatment with avelumab will continue until disease progression.
• Drug: Avelumab
  Anti-PD-L1 antibody at X3 mg IV every 3 weeks to optimize dosing for expansion. Treatment with avelumab will continue until disease progression
• Drug: Avelumab
  Anti-PD-L1 antibody at X3 mg IV every 2 weeks to optimize dosing for expansion. Treatment with avelumab will continue until disease progression
• Drug: Avelumab
  Anti-PD-L1 antibody at X mg IV every 2 weeks. Treatment with avelumab will continue until disease progression
• Drug: Avelumab
  Anti-PD-L1 antibody at X1 mg IV every 2 weeks which can be escalated to X4 mg every 2 weeks based on safety and efficacy. Treatment with avelumab will continue until disease progression.

• Experimental: Lead-in phase-Cohort A
  X1 mg IV every 2 weeks
  Intervention: Drug: Avelumab
• Experimental: Lead-in phase-Cohort B
  X2 mg IV every 2 weeks
  Intervention: Drug: Avelumab
• Experimental: Lead-in phase-Cohort C
  X3 mg IV every 3 weeks
  Intervention: Drug: Avelumab
• Experimental: Lead-in phase-Cohort D
  X4 mg IV every 2 weeks
  Intervention: Drug: Avelumab
• Experimental: Lead-in phase-Cohort E
  X5 mg IV every 2 weeks
  Intervention: Drug: Avelumab
• Experimental: Expansion phase
  X1 mg IV every 2 weeks followed by X1 or X4 mg every 2 weeks
  Intervention: Drug: Avelumab

KEY INCLUSION CRITERIA

• Histological confirmation of classical Hodgkin's Lymphoma (cHL) with relapsed or refractory disease who, for the lead-in phase, either have had a prior autologous or allogeneic HSCT or are not eligible for HSCT, and , for the expansion phase, have had a prior allogeneic HSCT. In the expansion phase there must be a documented CD3+ donor chimerism of ?20%.
• Patients must be off previous cHL therapy for at least 28 days prior to randomization in the lead-in phase/first dose of study treatment in the expansion phase.
• At least 1 fluorodeoxyglucose (FDG) PET avid (Deauville 4/5) measurable lesion >1.5 cm on PET-CT scan as defined by the Response Criteria for Malignant Lymphoma (for the lead-in phase) and the Lugano Classification (for the expansion phase) that has not previously been irradiated.
• Expansion phase: Required "de novo" or "archival" tumor biopsy, as well as required on treatment biopsy
• Estern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

KEY EXCLUSION CRITERIA

• Patients with prior allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) who have had:

  1. Lead-in phase: allo HSCT performed <12 months prior to randomization. Expansion phase: allo-HSCT performed ?4 months prior to the first dose of study treatment. NOTE: Patients who have had allo-HSCT performed >4 months prior to the first dose of study treatment must have discontinued all immunosuppressive therapy, and must have no clinical evidence of GVHD; or
  2. Immunosuppressive treatment for acute or chronic GVHD within 3 months prior to randomization for the lead-in phase or prior to the first dose of study treatment for the expansion phase (with the exception of those patients who required 15 mg/day oral prednisone or equivalent). Patients who required 15 mg/day oral prednisone or equivalent must have discontinued it within 7 days prior to first dose of study treatment; or
  3. Acute Grade 3 or Grade 4 GVHD at any time in the past (as defined by the modified Seattle Glucksberg criteria (Consensus Conference on Acute GVHD Grading Criteria); or
  4. Prior chronic GVHD (as defined by the NIH Consensus Development Project) that persisted for >6 months and required systemic immunosuppression (with the exception of those patients who required 15 mg/day oral prednisone or equivalent). Patients who required 15 mg/day oral prednisone or equivalent must have discontinued it within 7 days prior to the first dose of study treatment; or
  5. A donor lymphocyte infusion (DLI) within 3 months prior to randomization for the lead-in phase or first dose of study treatment for the expansion phase.

• Prior therapy with an anti PD 1 or anti PD L1 mAb.

  1. Lead-in Phase: May be enrolled if patient stopped prior anti PD1 or anti-PD-L1 therapy more than one year prior to randomization and had a documented prior response.
  2. Expansion Phase: Prior therapy with an anti-PD-1 or anti-PD-L1 agent following allo-HSCT is prohibited unless the therapy was stopped more than one year prior to the first dose of study treatment, and the patient had a documented prior response. NOTE: Prior therapy with an anti-PD-1 or anti-PD-L1 agent prior to allo-HSCT is permitted with no time limits and irrespective of a documented response.
  3. Patients with a history of ?Grade 3 anti-PD-1 or anti-PD-L1-related immune toxicity are not eligible.