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: February 29, 2024
• 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: February 29, 2024
• Actual Study Start Date: December 6, 2018
• Actual Primary Completion Date: November 10, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 8, 2024)

• Pathological Complete Response (pCR) in modified intent-to-treat (mITT) population [ Time Frame: Up to approximately 15 weeks after randomization ]
  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) in modified intent to treat (mITT) population [ Time Frame: Up to 5.5 years after first patient randomized. ]
  An event is 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: February 8, 2024)

• Disease-free survival (DFS) in modified resected population [ Time Frame: From date of randomization to approximately 5.5 years after date of resection ]
• Major Pathological Response (mPR) in modified intent to treat (mITT) population [ Time Frame: Up to approximately 15 weeks after randomization ]
• Overall Survival (OS) in modified intent to treat (mITT) population [ Time Frame: From date of randomization to 5.5 years after randomization ]
• Event-free survival (EFS) in PD-L1-TC ≥1% patients in modified intent to treat (mITT) population [ Time Frame: From date of randomization to 5.5 years after randomization ]
• pCR in PD-L1-TC ≥1% patients in modified intent to treat (mITT) population [ Time Frame: Up to approximately 15 weeks after randomization ]
• Disease-Free Survival (DFS) in PD-L1-TC ≥1% patients in modified resected population [ Time Frame: From date of randomization to 5.5 years after date of resection ]
• Major Pathological Response (mPR) in PD-L1-TC ≥1% patients in modified intent to treat (mITT) population [ Time Frame: Up to approximately 15 weeks after randomization ]
• Overall Survival (OS) in PD-L1-TC ≥1% patients in modified intent to treat (mITT) population [ 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 durvalumab + chemotherapy prior to surgery followed by durvalumab post-surgery compared with placebo + chemotherapy 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 durvalumab + chemotherapy prior to surgery followed by durvalumab post-surgery compared with placebo + chemotherapy 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 [ 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: February 8, 2024): Number of participants with adverse events as assessed by CTCAE v5.0 [ Time Frame: From date of randomization to 3 months after last dose of IP ]
• 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
  1500mg on Day 1 of each 3-week cycle for 4 cycles during the neoadjuvant period and 1500mg on Day 1 of each 4-week cycle for 12 cycles during the adjuvant period
  Other Name: MEDI4736
• Other: Placebo
  Day 1 of each 3-week cycle for 4 cycles during the neoadjuvant period and Day 1 of each 4-week cycle for 12 cycles during the adjuvant period
• Drug: Carboplatin
  Area under the curve of 5/6 on Day 1 of each 3-week cycle for 4 cycles
• Drug: Cisplatin
  75 mg/m2 on Day 1 of each 3-week cycle, for 4 cycles
• Drug: Pemetrexed
  500 mg/m2 on Day 1 of each 3-week cycle for 4 cycles.
• Drug: Paclitaxel
  200mg/m2 on Day 1 of each 3-week cycle for 4 cycles.
• Drug: Gemcitabine
  1250 mg/m2 on Day 1 and Day 8 of each 3-week cycle, for 4 cycles.
• Procedure: Surgery
  Expected within 40 days from the last dose of IP following the completion of neoadjuvant treatment (4 cycles of platinum based chemotherapy concurrent with durvalumab or placebo)

Study Arms

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

  Patients will receive durvalumab 1500 mg in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by durvalumab 1500 mg monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity

  The platinum-based chemotherapy will be based on tumour histology and Investigator discretion:

  • cisplatin with pemetrexed
  • carboplatin with pemetrexed
  • carboplatin with paclitaxel
  • cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment)
  Interventions:

  • Drug: Durvalumab
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Pemetrexed
  • Drug: Paclitaxel
  • Drug: Gemcitabine
  • Procedure: Surgery
• Placebo Comparator: Arm 2: Placebo with platinum-based chemotherapy

  Patients will receive placebo in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by placebo monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity

  The platinum-based chemotherapy will be based on tumour histology and Investigator discretion:

  • cisplatin with pemetrexed
  • carboplatin with pemetrexed
  • carboplatin with paclitaxel
  • cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment)
  Interventions:

  • Other: Placebo
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Pemetrexed
  • Drug: Paclitaxel
  • Drug: Gemcitabine
  • Procedure: Surgery

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 31, 2023): 826
• Original Estimated Enrollment (submitted: January 8, 2019): 300
• Estimated Study Completion Date: September 11, 2028
• Actual Primary Completion Date: November 10, 2022 (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; 2018-002997-29 ( EudraCT Number )
• 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 Center

• PRS Account: AstraZeneca
• Verification Date: February 2024