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

• ClinicalTrials.gov Identifier: NCT03800134
• Recruitment Status: Active, not recruiting
• First Posted: January 11, 2019
• Last Update Posted: April 18, 2023
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: December 7, 2018
• First Posted Date: January 11, 2019
• Last Update Posted Date: April 18, 2023
• Actual Study Start Date: December 6, 2018
• Estimated Primary Completion Date: April 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 8, 2022)

• Pathological Complete Response (pCR) in modified intent-to-treat (mITT) [ Time Frame: From screening pathology to an average of 15 weeks after first dose. ]
  Defined as the lack of any viable tumour cells after complete evaluation in the resected lung cancer specimen and all sampled regional lymph nodes.
• Event-Free Survival (EFS) [ Time Frame: Up to 5.5 years after first patient randomized. ]
  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.

• Original Primary Outcome Measures (submitted: January 8, 2019): Major Pathological Response (mPR) [ Time Frame: From screening pathology to an average of 15 weeks after first dose. ]

Current Secondary Outcome Measures (submitted: May 26, 2021)

• Disease-free survival (DFS) in modified resected population [ Time Frame: From date of randomization to 5.5 years after date of resection ]
• Major Pathological Response (mPR) [ Time Frame: From screening pathology to an average of 15 weeks after first dose. ]
• Overall Survival (OS) [ Time Frame: From date of randomization to 5.5 years after randomization ]
• Event-free survival (EFS) in PD-L1-TC ≥1% positive patients [ Time Frame: From date of randomization to 5.5 years after randomization ]
• pCR in PD-L1-TC ≥1% positive patients [ Time Frame: From screening pathology to an average of 15 weeks after first dose ]
• Disease-Free Survival (DFS) in PD-L1-TC ≥1% positive patients [ Time Frame: From date of randomization to 5.5 years after date of resection ]
• Major Pathological Response (mPR) in PD-L1-TC ≥1% positive patients [ Time Frame: From screening pathology to an average of 15 weeks after first dose. ]
• Overall Survival (OS) in PD-L1-TC ≥1% positive patients [ Time Frame: 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 [ Time Frame: From date of screening to 6 months after last dose of IP ]
  To assess disease-related symptoms, functioning, and global health status/quality of life in patients.
• 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 [ Time Frame: From date of screening to 6 months after last dose of IP ]
  To assess disease-related symptoms, functioning, and global health status/quality of life in patients.
• To assess the PK of durvalumab in blood (through concentration) [ Time Frame: From date of randomization to 2 months after resection ]
  To assess concentration of durvalumab in bloodstream.
• Presence of ADA for durvalumab [ Time Frame: From date of randomization to 3 months after last dose of IP ]
  To evaluate the presence of antibodies following treatment with study medications.

Original Secondary Outcome Measures (submitted: January 8, 2019)

• Pathological complete response (pCR) [ Time Frame: From screening pathology to an average of 15 weeks after first dose. ]
• Overall Survival (OS) [ Time Frame: From date of randomization to 5.5 years after randomization ]
• Event-free survival (EFS) [ Time Frame: From date of randomization to 5.5 years after randomization ]
• Disease-free survival (DFS) [ Time Frame: From date of randomization to 5.5 years after date or resection ]
• 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 [ Time Frame: From date of screening to 6 months after last dose of IP ]
• To assess the PK of durvalumab in blood (through concentration) [ Time Frame: From date of randomization to 2 months after resection ]
• Presence of ADA for durvalumab [ Time Frame: From date of randomization to 3 months after last dose of IP ]
• mPR in PD-L1-TC positive patients [ Time Frame: From screening pathology to an average of 15 weeks after first dose ]
• 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 [ Time Frame: From date of screening to 6 months after last dose of IP ]

• Current Other Pre-specified Outcome Measures (submitted: May 26, 2021): Number of participants with all adverse events as assessed by CTCAE v5.0 [ Time Frame: 64 months ]
• Original Other Pre-specified Outcome Measures (submitted: January 8, 2019): Number of participants with all adverse events as assessed by CTCAE v4.0 in durva + chemo prior to surgery followed by durva post-surgery compared with placebo + chemo prior to surgery followed by placebo post-surgery [ Time Frame: 82 months ]

Descriptive Information

• Brief Title: A Study of Neoadjuvant/Adjuvant Durvalumab for the Treatment of Patients With Resectable Non-small Cell Lung Cancer
• Official Title: 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)
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Care Provider); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer

Intervention

• Drug: Durvalumab
  Durvalumab IV (intravenous infusion)
  Other Name: MEDI4736
• Other: Placebo
  Placebo IV (intravenous infusion)
• Drug: Carboplatin/Paclitaxel
  Carboplatin/Paclitaxel, as per standard of care
• Drug: Cisplatin/Gemcitabine
  Cisplatin/Gemcitabine, as per standard of care
• Drug: Pemetrexed/Cisplatin
  Pemetrexed/Cisplatin, as per standard of care
• Drug: Pemetrexed/Carboplatin
  Pemetrexed/Carboplatin, as per standard of care

Study Arms

• Experimental: Arm 1: Durvalumab + platinum-based chemotherapy

  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
  Interventions:

  • Drug: Durvalumab
  • Drug: Carboplatin/Paclitaxel
  • Drug: Cisplatin/Gemcitabine
  • Drug: Pemetrexed/Cisplatin
  • Drug: Pemetrexed/Carboplatin
• Placebo Comparator: Arm 2: Placebo + platinum-based chemotherapy

  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
  Interventions:

  • Other: Placebo
  • Drug: Carboplatin/Paclitaxel
  • Drug: Cisplatin/Gemcitabine
  • Drug: Pemetrexed/Cisplatin
  • Drug: Pemetrexed/Carboplatin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: November 18, 2022): 825
• Original Estimated Enrollment (submitted: January 8, 2019): 300
• Estimated Study Completion Date: April 30, 2024
• Estimated Primary Completion Date: April 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 120 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Costa Rica, France, Germany, Hungary, India, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Peru, Philippines, Poland, Romania, Russian Federation, Spain, Taiwan, Thailand, United States, Vietnam
• Removed Location Countries: Puerto Rico, Ukraine

Administrative Information

• NCT Number: NCT03800134
• Other Study ID Numbers: D9106C00001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Current Responsible Party: AstraZeneca
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: John Heymach, MD; UT MD Anderson Cancer Institute

• PRS Account: AstraZeneca
• Verification Date: April 2023