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

AstraZeneca

Status and phase: Active, not recruiting; Phase 3

Conditions: Non-Small Cell Lung Cancer

Treatments: Drug: Durvalumab; Procedure: Surgery; Drug: Carboplatin; Drug: Paclitaxel; Other: Placebo; Drug: Gemcitabine; Drug: Cisplatin; Drug: Pemetrexed

Study type: Interventional

Funder types: Industry

Identifiers

NCT03800134

D9106C00001

2018-002997-29 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 826 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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826 participants in 2 patient groups, including a placebo group

Arm 1: Durvalumab with platinum-based chemotherapy

Experimental group

Description:

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)

Treatment:

Drug: Pemetrexed

Drug: Cisplatin

Drug: Gemcitabine

Drug: Paclitaxel

Drug: Carboplatin

Procedure: Surgery

Drug: Durvalumab

Arm 2: Placebo with platinum-based chemotherapy

Placebo Comparator group

Description:

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)

Treatment:

Drug: Pemetrexed

Drug: Cisplatin

Drug: Gemcitabine

Other: Placebo

Drug: Paclitaxel

Drug: Carboplatin

Procedure: Surgery