Patient case: 48-year-old female with melanoma; genetic feature: tumor cells with >50% membranous PD-L1 expression

Clinical trial: A Study of Combination Therapies With Viagenpumatucel-L (HS-110) in Patients With Non-Small Cell Lung Cancer

Summary: This study will test whether vaccination with viagenpumatucel-L combined with strategies to modulate the immune response is safe for patients with non-small cell lung adenocarcinoma who have failed at least one prior line of therapy for incurable or metastatic disease. These methods collectively use the body's immune system to target the patient's own tumor. Immunosuppression hinders than response, and may develop in NSCLC patients in a variety of ways, such as activation of checkpoint pathways in the tumor microenvironment. Drugs that disrupt checkpoint molecule signaling like anti-PD-1 monoclonal antibodies nivolumab, may release this brake on the immune system. Tumor expression of PD-L1 plays an important role in patient response to checkpoint inhibitors; in general, clinical response to checkpoint inhibitors requires tumor expression of PD-L1 and presence of Tumor Infiltrating Lymphocytes (TIL). Combining viagenpumatucel-L with anti-PD-1 agents may enhance the vaccine's anti-tumor activity while prolonging or increasing the efficacy of the checkpoint inhibitor.


Eligibility: Inclusion Criteria:
  -  Non-small cell lung adenocarcinoma
  -  One site of measureable disease by RECIST 1.1
  -  Received at least one prior line of therapy for incurable or metastatic NSCLC
  -  Life expectancy ≥18 weeks
  -  Disease progression at study entry
  -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1; PS=2 patients may be considered
  -  Central nervous system (CNS) metastases may be permitted but must be treated and neurologically stable
  -  Adequate laboratory parameters
  -  Willing and able to comply with the protocol and sign informed consent
  -  Female patients who are of childbearing potential and fertile male patients must agree to use an effective form of contraception throughout study participation
  -  Willing to provide archival or fresh tumor biopsy at Screening and Week 10
  -  Suitable for treatment with nivolumab per package insert
  Exclusion Criteria:
  -  Received systemic anticancer therapy within the previous 21 days
  -  Human immunodeficiency virus (HIV), hepatitis B or C, or severe/uncontrolled infections or concurrent illness, unrelated to the tumor, requiring active therapy
  -  Any condition requiring concurrent systemic immunosuppressive therapy
  -  Known immunodeficiency disorders, either primary or acquired
  -  Known leptomeningeal disease
  -  Active malignancies within 12 months with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
  -  Pregnant or breastfeeding
  -  Prior treatment with a cancer vaccine for this indication
  -  Prior participation in a clinical study of viagenpumatucel-L
  -  Administration of a live, attenuated vaccine within 30 days prior to first dose of study drug
  -  Active, known or suspected autoimmune disease
  -  Prior treatment of checkpoint inhibitor

Relevance to patient case: not relevant