C349 Bronchus or lung, unspecified Bronchus or lung, unspecified
Conditions
Interventions
None listed
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Informed consent 1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol 2. Provision of signed and dated written ICF prior to any mandatory study specific procedures, sampling, and analyses 3. Provision of signed and dated written ICF prior to collection of sample for genetic analysis Age 4. Age =18 years at the time of screening. For patients aged 3 cm, central tumor, or clinical N1 (cN1), then it is recommended that nodal status be proven by biopsy via endobronchial ultrasound, mediastinoscopy, or thoracoscopy. See Section 6.1.3 (preoperative mediastinal lymph node staging) for more details. - Mandatory brain magnetic resonance imaging (MRI; preferred) with IV contrast or brain CT with IV contrast at the time of staging. 6. World Health Organization (WHO)/ECOG PS of 0 or 1 at enrollment 7. At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline. Tumor assessment by CT or MRI scan must be performed within 28 days prior to randomization. 8. 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. 9. Adequate organ and marrow function as defined below: - Hemoglobin =9.0 g/dL - Absolute neutrophil count =1.5 × 109/L - Platelet count =100 × 109/L - Serum bilirubin =1.5 × the upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome, who will be allowed in consultation with their physician. - ALT and AST =2.5 × ULN - Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL >40 mL/min as determined by Cockcroft-Gault (using actual body WT) 10. Must have a life expectancy of at least 12 weeks Weight 11. Body WT >30 kg Sex 12. Male and/or female Tumor sample requirements: 13. Confirmation of a patient’s tumor PD-L1 status must occur prior to randomization using Ventana PD-L1 (SP263) immunohistochemistry (IHC) assay applied to formalin fixed paraffin embedded tissue sample with testing completed by the central laboratory. Samples for PD-L1 testing may include the following: - Newly acquired tumor tissue (preferred) or archival tissue (<3 months old). - If the patient’s PD-L1 status has already been assessed using the analytically validated Ventana assay as a part of the screening process for another AstraZeneca study, this test re
Exclusion criteria
Exclusion criteria: Medical conditions 1 History of allogeneic organ transplantation 2 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 [eg, granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, or uveitis]). 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 3 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 4 History of another primary malignancy, except for the following: - Malignancy treated with curative intent and with no known active disease =5 years 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 5 History of active primary immunodeficiency 6 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 (known positive hepatitis B virus surface antigen [HBsAg] result), hepatitis C virus (HCV), or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved hepatitis B virus (HBV) infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA). 7 Deemed unresectable NSCLC by multidisciplinary evaluation that must include a thoracic surgeon who perform lung cancer surgery as a significant part of their practice 8 Patients who have pre-operative radiotherapy treatment as part of their care plan 9 Patients who have brain metastases or spinal cord compression. All patients will have an MRI (preferred) or high-quality CT with IV contrast of the brain, prior to study entry. 10 Stage IIIB N3 and Stages IIIC, IVA, and IVB NSCLC 11 Mean QT interval corrected for heart rate using Fridericia´s formula (QTcF) =470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart) 12 Mixed small cell and NSCLC histology 13 Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients 14 Any medical contraindication to treatment with platinum-based doublet chemotherapy as listed in the local labelling 15 Patients who are candidates to undergo only segmentectomies or wedge resections Prior/concomitant therapy 16 Any concurrent chemotherapy, IP, biologic, o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Investigator assessment using RECIST1.1 NAME OF THE RESULT: Event-free survival (EFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization until disease progression or death;10% or less residual viable tumor tissue in lung primary tumor after neoadjuvant treatment at the time of resection NAME OF THE RESULT: Major pathological response (mPR) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Since begining of neoadjuvant treatment, until surgery | — |
Secondary
| Measure | Time frame |
|---|---|
| Investigator assessment using RECIST1.1 NAME OF THE RESULT: Event-free survival (EFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization until disease progression or death;10% or less residual viable tumor tissue in lung primary tumor after neoadjuvant treatment at the time of resection NAME OF THE RESULT: Major pathological response (mPR) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Since begining of neoadjuvant treatment, until surgery;Efficacy of durvalumab + chemotherapy administered prior to surgery followed by durvalumab post-surgery compared with placebo + chemotherapy administered prior to surgery, followed by placebo post-surgery in terms of DFS NAME OF THE RESULT: Disease Free survival (DFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Since randomization until disease progression or death;Absence of any residual viable tumor in the primary lung lesion and lymph nodes at the time of surgical resection NAME OF THE RESULT: Pathological complete response (pCR) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Since neoadjuvant therapy until surgery;Efficacy of durvalumab + chemotherapy administered prior to surgery followed by durvalumab post-surgery compared with placebo + chemotherapy administered prior to surgery followed by placebo post-surgery in terms of OS NAME OF THE RESULT: Overall survival PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Since randomization until death | — |
Countries
Argentina, Austria, Belgium, Brazil, Chile, China, Costa Rica, France, Germany, Hungaria, India, Japan, Korea South, Netherlands, Peru, Philippines, Poland, Romania, Russian Federation, Spain, Taiwan, Thailand, United States, Vietnam
Outcome results
None listed