A Phase III, Open Label, Randomised, Multi-centre, International Study of MEDI4736, 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 (Stage IIIB-IV) Who Have Received at Least Two Prior Systemic Treatment Regimens Including One Platinum Based Chemotherapy Regimen and Do Not Have Known EGFR TK Activating Mutations or ALK Rearrangements (ARCTIC).

D4191C00004

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®)

2015-01-13

2018-02-09

2023-08-30

Completed

Early phase I

597

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)

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 597, 'type': 'ACTUAL'}}

2023-10-11