Durvalumab in Combination with Standard Chemotherapy for Treatment of Stage IV Non-small Cell Lung Cancer in Patients with HIV, Hepatitis B, or Hepatitis C

Inclusion Criteria

• Patients with stage IV NSCLC who had undergone no previous systemic therapy for stage IV disease
• Cohort 1: Patients with HIV must be on an effective combination anti-retroviral therapy (cART) regimen for >= 4 weeks
• Cohort 2: Patients with chronic HBV infection will be eligible. Patients with positive hepatitis B core antibody (anti-HBc) but negative surface antigen (HBsAg) will be eligible. Those with detectable HBV deoxyribonucleic acid (DNA) who are negative for HBsAg will also be eligible. For hepatitis C, patients with detectable HCV RNA will be eligible. Those who have completed antiviral therapy for HCV and undetectable HCV RNA will also be eligible
• Age >= 18 years at time of study entry
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Body weight > 30 kg
• Hemoglobin >= 9.0 g/dL
• Absolute neutrophil count (ANC) >= 1,000 per mm^3
• Platelet count >= 100,000 per mm^3
• CD4 T-cell count >= 100 per mm^3 for HIV-infected patients
• Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =< 5 x ULN
• Measured creatinine clearance (CL) > 40 mL/min or calculated creatinine CL > 40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: * Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy) * Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
• Must have a life expectancy of at least 12 weeks

Exclusion Criteria

• Sensitizing EGFR mutations (deletion in exon 19, L858R in exon 21, G719X, and L861Q) and/or ALK translocations by locally approved laboratory testing including blood-based liquid biopsy
• Coinfection of HIV + HBV or HIV + HCV (coinfection of HIV and HCV allowed if HCV is cured). Coinfection of HBV and HCV is allowed if otherwise eligible
• No measurable disease
• Receipt of the last dose of anticancer therapy (chemotherapy, targeted therapy) =< 21 days prior to the first dose of study treatment
• Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade >= 2 from previous anticancer therapy (chemotherapy, targeted therapy, radiation therapy) with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
• Patients who have had whole brain radiation therapy (WBRT) during the previous 2 weeks before treatment (no washout period is required for patients who have received stereotactic body radiation therapy)
• Subject has had major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks prior to starting study drug or has not recovered from side effects of such procedure (>= grade 2 adverse event [AE] related to such procedure). Video-assisted thoracic surgery (VATS) and mediastinoscopy will not be counted as major surgery and subject can be enrolled in the study >= 1 week after the procedure
• History of allogenic organ transplantation
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion: * Patients with vitiligo or alopecia * Patients with hypothyroidism (e.g., 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
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, 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
• Patients with prior or concurrent 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
• Previously untreated central nervous system (CNS) metastases or leptomeningeal disease. Patients who have had whole brain radiation therapy (WBRT) during the previous 2 weeks before treatment (no washout period is required for patients who have received stereotactic body radiation therapy)
• Active tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice)
• Current or prior use of immunosuppressive medication within 7 days before the first dose of durvalumab. The following are exceptions to this criterion: * Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) * Systemic corticosteroids at doses not to exceed 20 mg/day of prednisone or its equivalent * Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication) * Decreasing dose of systemic corticosteroids after radiation therapy for brain metastasis
• Receipt of live attenuated vaccine within 30 days prior to the first dose of investigational product (IP). Note: Patients, if enrolled, should not receive live vaccine whilst receiving study treatment and up to 30 days after the last dose of IP
• Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
• Patients who have received prior anti–PD-1, anti PD-L1 or anti CTLA-4 within 12 months of the first dose of durvalumab
• Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements