This is a phase II trial of durvalumab and tremelimumab in combination of platinum-based chemotherapy. Patients with stage IV Non-Small-Cell-Lung Cancer (NSCLC) with human immunodeficiency virus (HIV) infection will be eligible. Patients will receive standard platinum-based chemotherapy plus durvalumab for 4 cycles (every 3 weeks), followed by durvalumab (with or without pemetrexed for non-squamous NSCLC) maintenance therapy. It is hypothesized that Durvalumab and tremelimumab in combination with standard chemotherapy is safe and effective for the treatment of stage IV NSCLC in patients with HIV infection.
Patients with stage IV NSCLC who had undergone no previous systemic therapy for stage IV disease.
Patients with HIV must be on an effective combination anti-retroviral therapy (cART) regimen for ≥ 4 weeks. Also, patients need to meet the following criteria.
Documented HIV viral load < 400 copies/mL
No AIDS-defining opportunistic infections within the last 12 months
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.
2. Coinfection of HIV + HBV (coinfection of HIV and HBV allowed if the patient is on appropriate anti-viral therapy for HBV) or HIV + HCV (coinfection of HIV and HCV allowed if HCV is cured or patient is on appropriate anti-viral therapy for hepatitis C). 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.
Single group
Durvalumab
Drugdurvalumab 1500 mg, intravenous, every 3 weeks for 4 cycles, followed by 1500 mg, intravenous, every 4 weeks (maintenance treatment)
Tremelimumab
Drugtremelimumab 75 mg, intravenous, every 3 weeks for 4 cycles. A dose of tremelimumab 75 mg will be given at week 16.
Adverse Events
Incidence of treatment-emergent Adverse Events according to NCI CTCAE v5.0.
Radiological Response
Radiological response will be evaluated using Recist Version 1.1 Criteria
Changes in Viral Load
Evaluate changes in viral load with study treatment
Change in Cytokine Secretion Assays
Cytokine secretion assays will be performed on blood samples before, during, and after treatment.
Correlation of Multiplex IHC to response
Baseline immune biomarkers (e.g. PD-L1 expression, composition of T cells in tumor microenvironment) using multiplex IHC will be compared between responders and non-responders to find predictive biomarkers associated with response to treatment.
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Georgetown University
Lead sponsor
AstraZeneca
Collaborator
