Carcinoma, Non- Small Cell Lung
Conditions
Interventions
Intravenous administration of Durvalumab or Placebo
Sponsors
Hibi Kazushige
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICFs and in the protocol. 2. Provision of signed and dated, written informed consent form prior to any mandatory study-specific procedures, sampling, and analyses. 3. Provision of signed and dated written optional genetic informed consent prior to collection of the optional sample for genetic analysis. This consent should be signed at the time of second screening. This optional sample and analyses are separate from the mandatory genetic testing consent included in ICF1. The following criteria must have been met at the time of surgery or at the time of the curative intent therapy (first screening): 4. Age 18 years or more at the time of screening (ICF1); 5. Male and/or female 6. Histologically confirmed NSCLC with resectable stage II-III disease who have undergone curative intent therapy (complete resection of the primary tumor +-neoadjuvant and/or adjuvant therapy) per SoC. Select stage IIIB (ie, T3N2 or T4N2) patients will be eligible, provided they are upstaged to T3N2 or T4N2 based on confirmed pathology after surgery. Patients who are staged as T3N2 or T4N2 prior to surgery are not eligible. 7. A contrast-enhanced CT/MRI scan of the chest and abdomen (including liver and adrenal glands) along with brain MRI (preferred) or brain CT with IV contrast must have been done for surgical planning prior to surgery. It is recommended that patients undergo combined FDG-PET (18F-Fluoro-deoxyglucose positron emission tomography) and CT scan (computerized tomography) within the 6 weeks prior to surgery in order to rule out detectable extrathoracic, extracranial metastasis and to assess for potential mediastinal lymph node involvement prior to surgery. If the positron emission tomography (PET) scan was not performed, or data from a PET is not available, patients may still be enrolled into the study provided appropriate imaging (CT/MRI) is performed prior to randomization. 8. Complete resection of the primary NSCLC is mandatory. Invasive (pre-operative or intra-operative) exploration of hilar and mediastinal lymph nodes must have been performed to confirm primary tumor nodal status (prior to or after surgery). Surgical resection of the primary NSCLC can occur by open thoracotomy or by video-assisted thoracic surgery (VATs) and resection can be achieved by segmentectomy, lobectomy, sleeve resection, bilobectomy or pneumonectomy. Patients undergoing wedge resection are not eligible for this study. Criteria for prior systemic chemotherapy/radiotherapy: 9. Patients should have completed (or be undergoing) curative intent therapy (surgery +- neoadjuvant and/or adjuvant therapy; adjuvant therapy can include PORT) with exceptions noted below: Patients who discontinue chemotherapy and/or PORT for toxicity prior to completion of all planned therapy are eligible. Patients who have not received any neoadjuvant and/or adjuvant chemotherapy, and meet all other eligibility criteria, may be eligible under the following circumstances: - All patients who are eligible for adjuvant chemotherapy MUST be offered adjuvant chemotherapy. - The patient has declined adjuvant chemotherapy, and in the opinion of the Investigator, this is the patient's final decision after receiving appropriate information and adequate time to make the decision. The patient's refusal of adjuvant chemotherapy must be documented. - If in the view of the Inves
Exclusion criteria
Exclusion criteria: Diagnostics assessments: 1. EGFR and/or ALK mutant as assessed either from the tumor biopsy taken prior to surgery or the resected tumor tissue. Testing must be performed using a wellvalidated, local regulatory-approved test. EGFR/ALK may be tested centrally if local testing is unavailable. 2. Mixed small cell and NSCLC histology. 3. Require re-resection or are deemed to have unresectable NSCLC by amultidisciplinary evaluation that must include a thoracic surgeon who performs lung cancer surgery as a significant part of their practice. 4. Baseline imaging demonstrating unequivocal evidence of RECIST 1.1-defined disease recurrence or evidence of clinical recurrence outside of imaging prior to randomization. In the event of lymphadenopathy on imaging that would lead to exclusion, histopathological confirmation of lymph node metastasis should be obtained prior to excluding a patient from the study. If pathological confirmation of lymph node metastasis is not technically feasible and imaging appearance are deemed unequivocal for relapse, the patient will be excluded. Medical conditions 5. History of allogeneic organ or bone marrow transplantation. 6. Non-leukocyte-depleted whole blood transfusion in 120 days of genetic sample collection 7. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion: Patients with vitiligo or alopecia Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement Any chronic skin condition that does not require systemic therapy Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician Patients with celiac disease controlled by diet alone 8. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active ILD, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent. 9. History of another primary malignancy except for Malignancy treated with curative intent and with no known active disease 5 years or more before the first dose of IP and of low potential risk for recurrence Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in-situ without evidence of disease 10. History of active primary immunodeficiency 11. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B virus (HBV) (known positive HBV surface antigen (HBsAg) result), hepatitis C virus (HCV), or human immunodeficiency virus (positive HIV 1/2 antibodies).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| DFS in PD-L1 TC 1% or more (using Investigator assessments according to RECIST 1.1) [ Time Frame: Approximately 5 years ] To assess the efficacy of durvalumab compared to placebo as measured by DFS in the PD-L1 TC 1% or more analysis set | — |
Countries
Australia, Belgium, Czechia, Germany, Greece, Hungary, India, Japan, Mexico, Netherlands, Peru, Poland, Republic of Korea, Spain, Switzerland, Taiwan, Turkey, United Kingdom, United States, Vietnam
Contacts
Public ContactKazushige Hibi
Astrazeneka K.K
Outcome results
None listed