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)

Phase 3

Completed

Conditions: Non-small cell lung cancer / lung cancer
10038666

Registration Number: NL-OMON45219

Lead Sponsor: Astra Zeneca

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 18

Inclusion Criteria

- At least 18 years of age
- Documented evidence of NSCLC (Stage IIIB/ IV disease)
- Disease progression or recurrence after both a platinum-baed 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
- 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 acute or chronic hepatitis B, C and HIV
- Any unresolved toxicity CTCAE >Grade 2 from previous anti-cancer therapy
- Known EGFR TK activating mutations or ALK rearrangements. Patients with EGFR TK inactivating mutations, e.g. exon 20, are eligible
- 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)

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Sub-study A (PD-L1-positive population)<br /><br>To assess the efficacy of MEDI4736 monotherapy compared with Standard of Care<br /><br>in terms of OS and PFS.<br /><br><br /><br>Sub-study B (PD-L1-negative population)<br /><br>To assess the efficacy of MEDI4736+tremelimumab treatment compared with<br /><br>Standard of Care in terms of OS and PFS.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>To further assess the efficacy of MEDI4736 compared with Standard of Care in<br /><br>terms of: OS12, ORR, DoR, APF6, APF12, and PFS2.<br /><br><br /><br>To assess the safety and tolerability profile.<br /><br><br /><br>To assess the PK of MEDI4736 and tremelimumab.<br /><br><br /><br>To investigate the immunogenicity of MEDI4736 and tremelimumab.<br /><br><br /><br>To assess symptoms and health-related QoL using EORTC QLQ-C30 v3 and LC13.<br /><br><br /><br>Sub-study B (PD-L1-negative population)<br /><br>To evaluate the efficacy of MEDI4736+tremelimumab treatment compared with a)<br /><br>MEDI4736 monotherapy and b) tremelimunab monotherapy in terms of PFS.</p><br>