Comparing 10 approaches for locally advanced or metastatic non-small cell lung cancer

Exclusion

• −HER2 mutation if previously known
• −Active primary immunodeficiency known HIV infection, or active chronic and resolved hepatitis B (positive hepatitis B virus surface antigen \[HBsAg+ve\] or hepatitis B virus core antibody (anti-HBc +ve) regardless of HBV DNA level)) or hepatitis C infection. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Patients should be tested for HIV prior to treatment assignment if required by local regulations or IRBResearch Ethics Board (REB)The independent committee that must approve a study before it can run.Read more →/EC
• −Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screeningScreeningThe checks done before joining, to see whether a study fits.Read more →
• −Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder and prior pneumonectomy
• −Active infection including tuberculosis and uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
• −Spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to controlControl groupThe group a new treatment is measured against.Read more → associated symptoms
• −Medical history of myocardial infarction within 6 months before treatment assignment, symptomatic CHF (New York Heart Association Class II to IV), clinically important cardiac arrhythmias, or a recent (\< 6 months) cardiovascular event including stroke
• −For Part 3, Part 4 and Part 5: Cardiomyopathy of any etiology, symptomatic CHF (as defined by New York Heart Association Class \> II), unstable angina pectoris, history of MI within the past 12 months, or cardiac arrhythmia are to be excluded. Patients with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before treatment assignment to rule out acute cardiopulmonary events.
• −Ascites or pericardial effusion that requires drainage, peritoneal shunt, Pleuroperitoneal shunt or CART (Concentrated Ascites Reinfusion Therapy)
• −For Part 3, Part 4 and Part 5: Active non-infectious skin disease (including any grade rash, urticarial, dermatitis, ulceration, or psoriasis) requiring systemic treatment, active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
• −Unresolved toxicities not yet resolved to Grade ≤ 1 or baselineBaselineYour starting measurements, taken before treatment begins.Read more → from previous anticancer therapy OR prior discontinuation of any planned study therapy due to toxicity.
• −For Part 3, Part 4 and Part 5: History of substance abuse or any other medical or psychological conditions that may, in the opinion of the InvestigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →, interfere with the subject's participation in the clinical study or evaluation of the clinical study results
• −For Part 3, Part 4 and Part 5: History of thromboembolic events within 3 months before the first dose of IP (limited to pulmonary embolism, deep vein thrombosis, or cerebral venous sinus thrombosis).
• −must not have any medical contraindication to platinum-based chemotherapy.
• −Part 3, Part 4 and Part 5 patients must not have had prior exposure to anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-TIGIT or any other experimental immunotherapy in any setting.