A Global Study to Assess the Effects of MEDI4736 (Durvalumab), Given as Monotherapy or in Combination With Tremelimumab Determined by PD-L1 Expression Versus Standard of Care in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer
Condition: Non - Small Cell Lung Cancer NSCLC
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Intervention: MEDI4736 (durvalumab); Vinorelbine; Gemcitabine; Erlotinib; MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4); tremelimumab (anti-CTLA4)
Intervention description: MEDI4736 (durvalumab) treatment by intravenous infusion; Vinorelbine by intravenous infusion. Administered at a dose of 30 mg/m2 iv on Days 1, 8, 15 and 22 of a 28-day cycle.; Gemcitabine by intravenous infusion. Administered at a dose of 1000 mg/m2 iv over 30 minutes on Days 1, 8, and 15 of a 28-day cycle.; Erlotinib administered at a dose of 150 mg once daily as a tablet for oral administration; MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4) treatment by intravenous infusion; tremelimumab (anti-CTLA4) treatment by intravenous infusion
Intervention MeSH terms: Gemcitabine; Erlotinib Hydrochloride; Durvalumab; Vinorelbine; Tremelimumab; Antibodies, Monoclonal
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 597.0
Sex: All
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No

Summary:

      This study is a Phase III, randomised, open label, multi-centre study assessing the efficacy
      and safety of MEDI4736 (durvalumab) versus Standard of Care in NSCLC patients with PD-L1
      positive tumours and the combination of MEDI4736 (durvalumab) plus tremelimumab
      (MEDI4736+treme) versus Standard of Care in NSCLC patients with PD-L1-negative tumours in the
      treatment of male and female patients with locally advanced or metastatic NSCLC (Stage
      IIIB-IV), who have received at least 2 prior systemic treatment regimens including 1
      platinum-based chemotherapy regimen for NSCLC. Patients with known EGFR (Epidermal growth
      factor receptor) tyrosine kinase (TK) activating mutations and anaplastic lymphoma kinase
      (ALK) rearrangements are not eligible for the study (prospective testing is not planned
      within this study). The Standard of Care options are: an EGFR tyrosine kinase inhibitor
      (erlotinib [TARCEVA®]), gemcitabine or vinorelbine (NAVELBINE®)
    

Eligibility criteria:

        Inclusion Criteria:

          -  Aged at least 18 years

          -  Documented evidence of NSCLC (Stage IIIB/ IV disease)

          -  Disease progression or recurrence after both a platinum-based chemotherapy regimen and
             at least 1 additional regimen for treatment of NSCLC

          -  World Health Organization (WHO) Performance Status of 0 or 1

          -  Estimated life expectancy more than 12 weeks

        Exclusion Criteria:

          -  Prior exposure to any anti-PD-1 or anti-PD-L1 antibody or anti-CTLA4

          -  Brain metastases or spinal cord compression unless asymptomatic, treated and stable
             (not requiring steroids)

          -  Active or prior documented autoimmune disease within the past 2 years

          -  Evidence of severe or uncontrolled systemic disease, including active bleeding
             diatheses or active infections including hepatitis B, C and HIV

          -  Any unresolved toxicity CTCAE (Common Terminology Criteria of Adverse Events) >Grade 2
             from previous anti-cancer therapy

          -  Known EGFR TK activating mutations or ALK rearrangements

          -  Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous
             immunotherapy agent, or any unresolved irAE >Grade 1

          -  Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative
             colitis)