A Study of Neoadjuvant/Adjuvant Durvalumab for the Treatment of Patients With Resectable Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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This is a Phase III, randomized, double-blind, placebo-controlled, multi-center international study assessing the activity of durvalumab and chemotherapy administered prior to surgery compared with placebo and chemotherapy administered prior to surgery in terms of pathological complete response.

Official Title
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A Phase III, Double-blind, Placebo-controlled, Multi-center International Study of Neoadjuvant/Adjuvant Durvalumab for the Treatment of Patients With Resectable Stages II and III Non-small Cell Lung Cancer (AEGEAN)

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Durvalumab
* Other: Placebo
* Drug: Carboplatin/Paclitaxel
* Drug: Cisplatin/Gemcitabine
* Drug: Pemetrexed/Cisplatin
* Drug: Pemetrexed/Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Newly diagnosed and previously untreated patients with histologically or cytologically documented NSCLC with resectable (Stage IIA to select [ie, N2] Stage IIIB) disease World Health Organization (WHO)/ECOG PS of 0 or 1 at enrollment At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 Target Lesion (TL) at baseline No prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies, excluding therapeutic anticancer vaccines Adequate organ and marrow function Confirmation of a patient's tumour PD-L1 status Provision of sufficient tumour biopsy sample for evaluation and confirmation of EGFR and ALK status Planned surgery must comprise lobectomy, sleeve resection, or bilobectomy Exclusion Criteria: History of allogeneic organ transplantation Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome) History of another primary malignancy History of active primary immunodeficiency Active infection including tuberculosis hepatitis B and C, or human immunodeficiency virus Deemed unresectable NSCLC by multidisciplinary evaluation Patients who have pre-operative radiotherapy treatment as part of their care plan Patients who have brain metastases or spinal cord compression Stage IIIB N3 and Stages IIIC, IVA, and IVB NSCLC Known allergy or hypersensitivity to any of the study drugs or excipients Existence of more than one primary tumour such as mixed small cell and NSCLC histology Patients whose planned surgery at enrollment includes any of the following procedures: pneumonectomy, segmentectomies, or wedge resections Patients with a documented test result confirming the presence of EGFRm or ALK translocation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Durvalumab + platinum-based chemotherapy<br>Durvalumab (MEDI4736) in concurrence with platinum-based chemotherapy. All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on tumour histology and Investigator discretion: carboplatin/paclitaxel cisplatin/gemcitabine pemetrexed/cisplatin pemetrexed/carboplatin | Drug: Durvalumab<br>* Durvalumab IV (intravenous infusion)<br>* Other names: MEDI4736;Drug: Carboplatin/Paclitaxel<br>* Carboplatin/Paclitaxel, as per standard of care<br>Drug: Cisplatin/Gemcitabine<br>* Cisplatin/Gemcitabine, as per standard of care<br>Drug: Pemetrexed/Cisplatin<br>* Pemetrexed/Cisplatin, as per standard of care<br>Drug: Pemetrexed/Carboplatin<br>* Pemetrexed/Carboplatin, as per standard of care<br>|
| Placebo Comparator: Arm 2: Placebo + platinum-based chemotherapy<br>Placebo in concurrence with platinum-based chemotherapy. All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on tumour histology and Investigator discretion: carboplatin/paclitaxel cisplatin/gemcitabine pemetrexed/cisplatin pemetrexed/carboplatin | Other: Placebo<br>* Placebo IV (intravenous infusion)<br>Drug: Carboplatin/Paclitaxel<br>* Carboplatin/Paclitaxel, as per standard of care<br>Drug: Cisplatin/Gemcitabine<br>* Cisplatin/Gemcitabine, as per standard of care<br>Drug: Pemetrexed/Cisplatin<br>* Pemetrexed/Cisplatin, as per standard of care<br>Drug: Pemetrexed/Carboplatin<br>* Pemetrexed/Carboplatin, as per standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological Complete Response (pCR) in modified intent-to-treat (mITT) | Defined as the lack of any viable tumour cells after complete evaluation in the resected lung cancer specimen and all sampled regional lymph nodes. | From screening pathology to an average of 15 weeks after first dose. | 
| Event-Free Survival (EFS) | An event defined as documented RECIST 1.1 local or distant recurrence of lung cancer; death due to any cause; disease progression that precludes surgery or discovered upon attempting surgery that prevents completion of surgery. | Up to 5.5 years after first patient randomized. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival (DFS) in modified resected population |  | From date of randomization to 5.5 years after date of resection | 
| Major Pathological Response (mPR) |  | From screening pathology to an average of 15 weeks after first dose. | 
| Overall Survival (OS) |  | From date of randomization to 5.5 years after randomization | 
| Event-free survival (EFS) in PD-L1-TC ≥1% positive patients |  | From date of randomization to 5.5 years after randomization | 
| pCR in PD-L1-TC ≥1% positive patients |  | From screening pathology to an average of 15 weeks after first dose | 
| Disease-Free Survival (DFS) in PD-L1-TC ≥1% positive patients |  | From date of randomization to 5.5 years after date of resection | 
| Major Pathological Response (mPR) in PD-L1-TC ≥1% positive patients |  | From screening pathology to an average of 15 weeks after first dose. | 
| Overall Survival (OS) in PD-L1-TC ≥1% positive patients |  | From date of randomization to 5.5 years after randomization. | 
| To assess disease-related symptoms and HRQoL (EORTC QLQ-C30) in patients treated with durva + chemo prior to surgery followed by durva post-surgery compared with placebo + chemo prior to surgery followed by placebo post-surgery | To assess disease-related symptoms, functioning, and global health status/quality of life in patients. | From date of screening to 6 months after last dose of IP | 
| To assess disease-related symptoms and HRQoL (EORTC QLQ-LC13) in patients treated with durva + chemo prior to surgery followed by durva post-surgery compared with placebo + chemo prior to surgery followed by placebo post-surgery | To assess disease-related symptoms, functioning, and global health status/quality of life in patients. | From date of screening to 6 months after last dose of IP | 
| To assess the PK of durvalumab in blood (through concentration) | To assess concentration of durvalumab in bloodstream. | From date of randomization to 2 months after resection | 
| Presence of ADA for durvalumab | To evaluate the presence of antibodies following treatment with study medications. | From date of randomization to 3 months after last dose of IP | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Resectable Non-small Cell Lung Cancer, NSCLC, Carcinoma, Non-small Cell Lung Cancer