Copanlisib for Treatment of Locally Advanced Unresectable Non-small Cell Lung Cancer When Starting Durvalumab

Inclusion Criteria

• Histologically confirmed NSCLC (e.g., adenocarcinoma, squamous cell) treated with concurrent chemoradiation
• Starting Durvalumab as consolidation therapy (either intravenously per current standard of care or subcutaneously on a clinical trial). Patient must have at least stable disease after chemoradiation (complete response [CR], partial response [PR], or stable disease [SD])
• Have at least one measurable lesion before initiation of chemoradiation therapy. Radiated lesion(s) can be counted as measurable disease if they have confirmed radiographic progression.
• Age >= 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2.
• Absolute neutrophil count >= 1,500/mcL.
• Platelets >= 100,000/mcL.
• Total bilirubin =< institutional upper limit of normal (ULN).
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN.
• Serum creatinine =< 1.5 x IULN.
• Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Patients with a prior malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

• Mixed non-small cell and small cell histology; known EGFR and/or ALK driver mutations.
• Patients who were treated with sequential chemoradiation therapy.
• Patients who are receiving any other investigational agents orally or intravenously.
• Autoimmune disease, such as rheumatoid arthritis, systemic lupus erythematosus, requiring systemic treatment with immunosuppressant in the past two years.
• Systemic steroid for other purpose exceeding 10 mg prednisone a day except local injection at the discretion of the investigator.
• Solid organ or bone marrow transplant recipients.
• History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function as judged by the investigator.
• Patients with uncontrolled inter-current illness such as hypertension, blood pressure (BP) > 150/90 mm Hg at the time of entry, diabetes Hemoglobin (HB)A1c > 8.5; or hypercholesterolemia not controlled, G3 or above.
• Patients with psychiatric illness/social situations that would limit compliance with study requirements and patients with seizure disorder not well controlled.
• Received live vaccine in the past 4 weeks.
• Pregnant or breastfeeding/lactating women.
• Receiving medications prohibited by the study. Examples of prohibited medications include the following: Strong CYP3A4/5 inhibitors; any medications that induce QT prolongation strongly; strong CYP3A4 inducers; Antiarrhythmic medications (other than beta blocker or digoxin); Anti-neoplastic drug (other than study drugs); Herbal remedies.
• New York Heart Association Class 3 or above.
• Myocardial infarction within the last 6 months.
• Unstable angina.
• Venous thromboembolism within last 3 months.
• Evidence or history of bleeding diathesis. Any hemorrhage or bleeding event >= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 within 4 weeks prior to the start of study medication.
• Proteinuria of >= CTCAE grade 3 as assessed by a 24 hour (h) protein quantification or estimated by urine protein: creatinine ratio > 3.5 on a random urine sample.
• Major surgeries within the last 28 days.
• Any illness or medical conditions that are unstable or could jeopardize the safety of patients and their compliance in the study.