A Global Study to Assess the Effects of MEDI4736 (Durvalumab) in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer

Phase 2

Completed

Brief Summary: A study to assess the Effects of MEDI4736 (Durvalumab) in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer in terms of efficacy, safety and tolerability

Detailed Description: This study is designed to investigate the efficacy, safety, tolerability of a new drug, MEDI4736 (Durvalumab), in patients with Locally Advanced or Metastatic Non Small Cell Lung Cancer. MEDI4736 will be investigated in patients who have received at least two prior treatment regimens including one platinum-based chemotherapy

Recruitment & Eligibility

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 and at least 1 additional regimen for treatment of NSCLC
World Health Organisation (WHO) Performance Status of 0 or 1
Estimated life expectancy of more than 12 weeks
Patient's tumour sample must be PD-L1 positive (≥25%of tumour cells with membrane staining (Cohort 1 and 2) or PD-L1 positive with ≥90% of tumour cells with membrane staining (Cohort 3))

Exclusion Criteria

Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
Brain metastases or spinal cord compression or unless asymptomatic, treated and stable (not requiring steroids).
Active or prior autoimmune disease or history of immunodeficiency
Evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses or active infections including hepatitis B, C and HIV.
Evidence of uncontrolled illness such as symptomatic congestive heart failure, uncontrolled hypertension or unstable angina pectoris.
Any unresolved toxicity CTCAE >Grade 2 from previous anti-cancer therapy.
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)

Arm && Interventions

Group	Intervention	Description
MEDI4736	MEDI4736	see below

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Responses recorded during initial 12 month treatment period (up to primary analysis DCO)	Patients commenced treatment with durvalumab on Day 1 and continued on a Q2W schedule for a maximum of 12 months. Tumor assessments using computed tomography / magnetic resonance imaging were performed every 8 weeks. Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) measurements as given by the Independent Central Review (ICR) were used to derive the primary variable of ORR .

Secondary Outcome Measures

Name	Time	Method
Time to Response (TTR)	Responses recorded during initial 12 month treatment period (up to primary analysis DCO)	TTR (per RECIST 1.1 as assessed by the ICR) is defined as the time from the date of first dose until the date of first documented response (which is subsequently confirmed). TTR was only analyzed for Cohort 2.
Duration of Response (DoR)	Time from response to progression, death, or last assessment (up to approximately 2 years 3 months for the primary analysis DCO)	DoR (per RECIST 1.1 as assessed by the ICR) was defined as the time from the date of first documented response (which was subsequently confirmed) until the first date of documented progression or death in the absence of disease progression (ie, date of PFS event or censoring - date of first response + 1). DoR was only analyzed for Cohort 2. Cohort 2: Median DoR was 12.3 months in the PD-L1 high (TC\>=25%) group at DCO (Q3 was NR). Of the 7 evaluable patients, the median DoR was not reached in the PD-L1 low/neg group (TC \<25%); therefore the DoR "number of participants analyzed" field has been entered as "0" and the DoR results field has been left blank.
Overall Survival (OS)	From date of first treatment until final DCO (up to approximately 3 years 8 months)	OS was defined as the time from the date of first dose until death due to any cause (ie, date of death or censoring - date of first dose + 1). Results are reported as median OS, calculated using the Kaplan-Meier methodology.