Patient case: 78-year-old female with sarcoma; genetic feature: MDM2

Clinical trial: Trial of CMB305 and Atezolizumab in Patients With Sarcoma

Summary: This is an open-label Phase 2 randomized study that will examine the use of the study agents, CMB305 (sequentially administered LV305 [a dendritic cell-targeting viral vector expressing the NY-ESO-1 gene] and G305 [NY-ESO-1 recombinant protein plus GLA-SE]) in combination with atezolizumab or atezolizumab alone, in patients with locally advanced, relapsed or metastatic sarcoma (synovial or myxoid/round cell liposarcoma) expressing the NY-ESO-1 protein.
  CMB305 is a novel approach designed to stimulate the body's immune system to fight the spread and growth of cancer in patients whose tumors express the NY-ESO-1 protein. LV305 will be given in a prime-boost approach with G305 to induce a potentially synergistic immunotherapeutic response in combination with atezolizumab.

Detailed description: This study is designed to investigate and examine the time to progression for CMB305 in combination with atezolizumab or atezolizumab alone in the treatment of patients with sarcoma expressing NY-ESO-1 protein.

Eligibility: Selected Inclusion Criteria:
  -  Locally advanced, relapsed, or metastatic sarcoma with measurable tumor burden following therapy, as defined by RECIST v1.1; the total of all lesions must be ≤12 cm (for synovial sarcoma) or ≤15 cm (for myxoid/round cell liposarcoma [MRCL]).
  -  Tumor histology consistent with synovial sarcoma or MRCL.
  -  Tumor specimen positive for NY-ESO-1 expression by IHC.
  -  Inadequate response, relapse, and/or unacceptable toxicity with ≥ 1 prior systemic, surgical, or radiation cancer therapies.
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  Selected Exclusion Criteria:
  -  Investigational therapy within 4 weeks prior to CMB305 dosing
  -  Prior administration of other NY-ESO-1-targeting immunotherapeutics.
  -  Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti PD-1, and anti PD-L1 therapeutic antibodies, or any other antibody or drug targeting T-cell costimulation.
  -  Treatment with systemic immunostimulatory agents (including but not limited to interleukin-2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to first dose.
  -  Significant immunosuppression.
  -  Other cancer therapies, including chemotherapy, radiation, biologics or kinase inhibitors within 3 weeks prior to the first scheduled dosing.
  -  History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
  -  History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), risk of pulmonary toxicity, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  -  History of other cancer within 3 years.
  -  Evidence of active tuberculosis or recent (<1 week prior to first scheduled dosing) clinically significant infection requiring systemic therapy.
  -  Evidence of active hepatitis B (HepB), hepatitis C (HepC), or Human Immunodeficiency Virus (HIV) infection.
  -  Known active or untreated central nervous system (CNS) metastases. - Pregnant, planning to become pregnant within 6 months of treatment, or nursing.
  -  Known allergy(ies) to any component of CMB305, atezolizumab, or severe allergic reactions to monoclonal antibodies, fusion proteins, or CHO cell products.

Relevance to patient case: not relevant