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: Paclitaxel; Procedure: Surgery; Drug: Gemcitabine; Other: Placebo; Drug: Durvalumab; Drug: Carboplatin; 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: Carboplatin

Procedure: Surgery

Drug: Gemcitabine

Drug: Durvalumab

Drug: Paclitaxel

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: Carboplatin

Procedure: Surgery

Drug: Gemcitabine

Other: Placebo

Drug: Paclitaxel