Completely resected primary stage IB (>4cm), II and IIIA non-small cell lung cancer MedDRA version: 21.1 Level: PT Classification code 10029520 Term: Non-small cell lung cancer stage IIIA System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10029517 Term: Non-small cell lung cancer stage I System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA ver
Conditions
Interventions
Product Name: MEDI4736
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Not assigned
CAS Number: 1428935-60-7
Current Sponsor code: MEDI4736
Other descriptive name: durv
Sponsors
Stichting NVALT studies
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically confirmed diagnosis of primary non-small cell carcinoma of the lung. Patients must have an adequate histopathology, must consent to release of an adequate histological specimen and the tissue blocks must be available for submission after registration. Patients with synchronous primary tumors will not be elegible - Patients must be classified post-operatively as Stage IB (= 4cm in the longest diameter), II or IIIA on the basis of pathologic criteria. - A pre-surgical PET scan of the thorax and a MRI or CT scan of the brain is considered standard of care and thus must be done prior to surgery. Patients in whom this was not done prior to surgery may still be enrolled providing that appropriate imaging is performed prior to randomization. - Complete surgical resection of the primary NSCLC is also mandatory. - Surgeons are encouraged to dissect or sample all accessible nodal levels in accordance with the European Society of Thoracic Surgeons guidelines. A minimum of three lobe specific mediastinal nodal stations (N2), one of which must include station 7, and at least one N1 station - inclusive of the ones removed with the pulmonary specimen must have been sampled at the end of the procedure. - If preoperative CT and/or PET are suspicious for mediastinal nodal involvement, invasive mediastinal staging with mediastinoscopy or EBUS-TBNA should be performed. - Surgery may consist of lobectomy, sleeve resection, bilobectomy or pneumonectomy as determined by the attending surgeon based on the intraoperative findings. Patients who have had only segmentectomies or wedge resections are not eligible for this study. - Pre-operative (neo-adjuvant) platinum based or other chemotherapy is not permissible. - Patients may have received prior post-operative platinum based chemotherapy as per standard of care. - Patients who have not received adjuvant chemotherapy, and meet all other eligibility criteria, may be eligible under the circumstances specified in the protocol. - No prior anticancer therapy for treatment of NSCLC other than standard post-operative adjuvant chemotherapy is permissible. - Pre-operative or post-operative or planned radiation therapy is not permissible. - Timing between surgery and adjuvant chemotherapy and randomization according to the protocol - The patient must have an ECOG performance status of 0, 1. - Hematology done within 14 days prior to randomization and with values within the ranges specified in the protocol - Biochemistry done within 14 days prior to randomization and with values within the ranges specified in the protocol - Other investigations detailed in the section 6 of the protocol must have been performed within the timelines indicated. - Patient able (i.e. sufficiently fluent) and willing to complete the questionnaires - Patient consent must be appropriately obtained - Patients must be accessible for treatment and follow-up - Protocol treatment is to begin within 2 working days of patient randomization. - Age of at least 18 years Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 605 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 495
Exclusion criteria
Exclusion criteria: - Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other solid tumours curatively treated with no evidence of disease for = 5 years following the end of treatment and which, in the opinion of the treating physician, do not have a substantial risk of recurrence of the prior malignancy. - A combination of small cell and non-small cell lung cancer or pulmonary carcinoid tumour. - History of autoimmune disease - History of primary immunodeficiency, history of allogenic organ transplant, use of immunosuppressive agents within 28 days of randomization or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy. - Live attenuated vaccination administered within 30 days prior to randomization. - History of hypersensitivity to MEDI4736 or any excipient. - Mean QTc correction > 470msec in screening ECG measured using standard institutional method or history of familial long QT syndrome. - Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction. Patients with a significant cardiac history, even if controlled, should have a LVEF > 50% within 12 weeks prior to randomization. - Concurrent treatment with other investigational drugs or anti-cancer therapy. - Patients with active or uncontrolled infections or with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol. - Pregnant or lactating women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess in comparison to placebo, the impact of adjuvant therapy with MEDI4736 given by intravenous infusion for one year on the disease free survival (DFS) of patients with completely resected (stage IB = 4cm, stage II or IIIA), non-small cell lung cancer that is PD-L1 positive.;Secondary Objective: - DFS in all randomized patients - OS in the MEDI4736 arm vs the placebo arm in patients with NSCLC that is PD-L1 positive - OS in the MEDI4736 arm vs the placebo arm in all randomized patients - Lung cancer specific survival in the MEDI4736 arm vs the placebo arm for patients with PD-L1+ NSCLC as well as all randomized patients - To evaluate the nature, severity, and frequency of toxicities, between arms - To evaluate the QoL between the two arms - To determine the survival benefits participants judge necessary to make adjuvant immunotherapy worthwhile, and the factors influencing their preferences - To determine the incremental cost effectiveness and cost utility ratios for MEDI4736 - To evaluate the prognostic and predictive significance of PD-L1 expression - To evaluate changes in blood and tissue based biomarkers after treatment with MEDI4736 and at the first disease event - To explore polymorphisms that may be associated with outcomes;Primary end point(s): DFS for patients with NSCLC that is PD-L1 positive.;Timepoint(s) of evaluation of this end point: Follow up for disease event and survival (q 12 weekly until 2 years from randomization, then q 6 months in year 3 then annually until disease event). After disease event follow for survival (q 6 months until 3 years from randomization, then annually). Primary Analysis of DFS: We will perform a primary analysis on DFS and an interim analysis on OS in the cohort with NSCLC that is PD-L1 positive when 210 DFS events have been observed, estimated to occur approximately 5.5 years after the start of the study. Final Analysis of DFS: The final analysis of DFS in the cohort of patients with NSCLC that is | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - DFS in all randomized patients. - OS for patients with NSCLC that is PD-L1 positive. - OS for all randomized patients. - Lung cancer specific survival for patients with NSCLC that is PD-L1 positive and all randomized patients. - Adverse effects and tolerability of MEDI4736. - Quality of life. - Survival benefits participants judge necessary to make adjuvant immunotherapy worthwhile. - Economic evaluation (cost effectiveness and cost utility). - Evaluation of predictive/prognostic significance of PD-L1 expression. - Evaluation of changes in plasma/serum cytokines and other blood and tissue based biomarkers after treatment with MEDI4736 and at disease event. - Exploratory pharmacogenomic assays (baseline only).;Timepoint(s) of evaluation of this end point: According to protocol schedules | — |
Countries
Australia, Bulgaria, Canada, France, Hungary, Italy, Korea, Republic of, Netherlands, New Zealand, Poland, Romania, Singapore, Spain, Taiwan, United States
Contacts
Public ContactResearch coordinator
StichtingNVALT studies
Outcome results
None listed