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

Study Overview
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Brief Summary
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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
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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

Official Title
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A Phase II,Non-comparative,Open Label, Multi-centre, International Study of MEDI4736, in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB-IV) Who Have Received at Least 2 Prior Systemic Treatment Regimens Including 1 Platinum-based Chemotherapy Regimen

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: MEDI4736


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI4736<br>see below | Drug: MEDI4736<br>* MEDI4736 (durvalumab) by intravenous infusion every two weeks. Treatment from Day 1 for a maximum of 12 months or study drug withdrawal if this occurs earlier. Patients who achieve CR, PR or SD through the end of the initial 12-month treatment period can restart treatment with MEDI4736 (durvalumab) when they eventually do progress. This retreatment period can continue for as long as the investigator considers to patient to be receiving clinical benefit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | 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 . | Responses recorded during initial 12 month treatment period (up to primary analysis DCO) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Response (TTR) | 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. | Responses recorded during initial 12 month treatment period (up to primary analysis DCO) | 
| Duration of Response (DoR) | 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. | Time from response to progression, death, or last assessment (up to approximately 2 years 3 months for the primary analysis DCO) | 
| Overall Survival (OS) | 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. | From date of first treatment until final DCO (up to approximately 3 years 8 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally advanced, metastatic, Non-Small Cell Lung Cancer, MEDI4736, Durvalumab, PD-L1