An Open-Label, Multi-Centre, Study to Assess the Safety of Fixed-Dose Durvalumab + Tremelimumab Combination Therapy or Durvalumab Monotherapy in Advanced Solid Malignancies.
Condition: Advanced Solid Malignancies
MeSH terms: Neoplasms
Study type: Interventional
Phase: Phase 3

Summary: 
      To evaluate the safety, tolerability, and anti-tumor activity of the combination of
      durvalumab + tremelimumab or durvalumab alone in different solid tumors.
    

Detailed description: 
      This is an open-label, multi-center, study to determine the short and long term safety of
      fixed doses of durvalumab 1500 mg + tremelimumab 75 mg combination therapy or durvalumab 1500
      mg monotherapy in patients with advanced solid malignancies. This study is modular in design,
      one or more of the modules will be opened in a given country / region based on local patient
      population prevalence, and results of feasibility studies. The total number of patients to be
      enrolled overall and in each module will depend on the types and number of tumor modules
      added to the main study and country-specific ancillary studies. The number of patients and
      sites to be involved in individual countries will be dependent on each module or ancillary
      study. This study consisted of a screening period, a treatment period, a 90 day safety
      follow-up period and a survival follow-up period. Patients will receive the investigation
      product (IP) via intravenous (IV) infusion once every 4 weeks (Q4W) in combination therapy or
      monotherapy as mentioned below - Combination therapy: Durvalumab 1,500 mg + tremelimumab 75
      mg on Week 0, for up to a maximum of 4 doses (or cycles) followed by durvalumab 1,500 mg
      starting 4 weeks after the last infusion of the combination or discontinuation of
      tremelimumab.

      Monotherapy: Durvalumab 1,500 mg on week 0.

      Patients will attend a safety follow-up visit 90 days after study treatment discontinuation.
      Thereafter, patients will be contacted by phone or electronic communication every 3 months
      for survival status up to 5 years following date of first patient treatment initiation. All
      patients will be followed for a minimum of 6 months following enrolment of last patient. It
      is anticipated that the total enrolment period for the overall study will be approximately 2
      to 3 years, with an overall duration of approximately 5 years
    

Intervention name(s): MEDI4736 (Durvalumab); MEDI4736 (Durvalumab) + Tremelimumab
Intervention type(s): Biological; Biological
Intervention description(s): A human monoclonal antibody (mAb) of the immunoglobulin G (IgG) 1 kappa subclass that blocks the interaction of PD-L1 (but not programmed cell death ligand-2) with PD-1 on T cells and CD80 (B7.1) on immune cells (IC).; Durvalumab: A human mAb of IgG 1 kappa subclass that blocks the interaction of PD-L1 (but not programmed cell death ligand-2) with PD-1 on T cells and CD80 (B7.1) on IC.
Tremelimumab: A human Ig G2 mAb that completely blocks the interaction of human CTLA-4 (cluster of differentiation [CD]152) with CD80 and CD86 and increase release of cytokines (interleukin [IL]-2 and interferon [IFN]-γ) from human T cells, peripheral blood mononuclear cells and whole blood.
Intervention MeSH terms: Durvalumab; Tremelimumab; Antibodies, Monoclonal
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Programmed death ligand 1 (PD-L1); Cytotoxic T-lymphocyte antigen-4 (CTLA-4); Durvalumab in combination with tremelimumab