Completely resected 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 version: 21.1 Level: PT Classification c
Conditions
Interventions
Product Code: 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
Clinipace Global Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically confirmed diagnosis of primary non-small cell carcinoma of the lung according to WHO Classification of Tumours (WHO/IARC Classification of Tumours, 4th Edition, Volume 7). Patients with largecell neuroendocrine carcinomas are not eligible. 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. Although T3N2M0 tumours have been reclassified to stage IIIB in the 8th edition of the IASLC staging system, these patients remain eligible (as stage IIIA under the 7th edition 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 strongly encouraged to dissect or sample all accessible nodal levels in accordance with the European Society of Thoracic Surgeons guidelines. It is recommended that a minimum of three lobe specific mediastinal nodal stations (N2), one of which should include station 7, and at least one N1 station - inclusive of the ones removed with the pulmonary specimen have been sampled at the end of the procedure. - If preoperative CT and/or PET are suspicious for mediastinal nodal involvement, it is recommended that invasive mediastinal staging with mediastinoscopy or EBUS-TBNA is 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. Note: Where a resection has been extended by means of a wedge resection of an adjacent lobe in order to ensure complete resection of a tumour at or crossing a fissure between lobes, as long as the margins are clear this is acceptable. Where the resection of a second tumour nodule, even where not considered to be a co-primary, is undertaken by means of a wedge resection of a separate lobe then the patient is not eligible. - 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 discontinue chemotherapy for toxicity prior to completion of all planned chemotherapy are eligible. If adjuvant platinum based chemotherapy is given, it is strongly recommended that this be started within 8 weeks of surgery. Patients must have recovered from all acute, reversible toxic effects from chemotherapy (excluding alopecia). - 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. - Patients with N2 disease only who receive adjuvant post-operative radiation therapy are eligible provided they meet the protocol specified timing criteria for surgery, adjuvant chemotherapy and
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 malignancies 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, pulmonary carcinoid tumour or large-cell neuroendocrine carcinoma (LCNEC).. - History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. NOTE: patients with Grave’s disease and/or psoriasis not requiring systemic therapy within the last two years from randomization and patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement are not excluded. - 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. * NOTE: Intranasal/inhaled corticosteroids or systemic steroids that do not to exceed 10 mg/day of prednisone or equivalent dose of an alternative corticosteroid are permissible. - Live attenuated vaccination administered within 30 days prior to randomization. - History of hypersensitivity to MEDI4736 or any excipient. - Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction within the previous year or cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects). Patients with a significant cardiac history, even if controlled, must 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. This includes but is not limited to: • known clinical diagnosis of tuberculosis; • known active hepatitis B infection (positive HBV surface antigen (HBsAg)). Patients with a past or resolved hepatitis B infection (defined as presence of hepatitis B core antibody (anti-HBc) and absence of HBSAg) are eligible; • known active hepatitis C infection. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RA; • known human immunodeficiency virus infection (positive HIV antibodies); • known pneumonitis or pulmonary fibrosis with clinically significant impairment of pulmonary function. - Pregnant or lactating women. Women of childbearing potential must have a urine pregnancy test proven negative within 14 days prior to randomization. Men and women of child-bearing potential must agree to use adequate contraception.
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 of patients with completely resected (stage IB > 4cm, stage II or IIIA), non-small cell lung cancer that is PD-L1 expression TC = 25% and EGFR-/ALK-.;Secondary Objective: -Compare DFS in MEDI4736 arm to placebo arm in remaining 5 patient sub-populations defined by PD-L1 expression levels and EGFR/ALK status - OS and Lung CSS in MEDI4736 arm vs placebo arm in six patient sub-populations defined by PD-L1 expression levels and EGFR/ALK status - Evaluate the nature, severity, and frequency of toxicities, between arms - Evaluate QoL between two arms the six patient sub-populations defined by PD-L1 expression levels and EGFR/ALK status - To determine the survival benefits participants judge necessary to make adjuvant immunotherapy worthwhile, and the factors influencing their preferences - 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): Disease free survival (DFS) for patients with NSCLC that is PD-L1 positive expression TC = 25%, and EGFR /ALK-.;Timepoint(s) of evaluation of this end point: Follow-up for disease event and survival (q12 weeekly until 2 years from randomization, then q6 months in year 3 then annualy until disease event). After disease event follow-up for survival (q6 months until 3 years from randomization, then annualy). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -DFS in the remaining 5 patient sub-populations defined by PD-L1 expression levels and EGFR/ALK status. - OS defined as the time from the randomization to the date of death of any cause, or censored at their last known alive date. - Lung cancer specific survival (CSS) defined as the time from the date of randomization to the date of patients died of lung cancer, or censored at the last contact date. A competing risk analysis will be used to test for difference in CSS between the two treatment arms;Timepoint(s) of evaluation of this end point: According to protocol schedules | — |
Countries
Australia, Bulgaria, Canada, China, France, Hungary, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Poland, Romania, Singapore, Spain, Taiwan, United States
Contacts
Public ContactEU Contact Point
Clinipace Global Ltd.
Outcome results
None listed