Study to Compare the Safety and Efficacy of CMB305 With Atezolizumab to Atezolizumab Alone in Participants With Sarcoma (IMDZ-C232/V943A-002)
Condition: Sarcoma; Myxoid/Round Cell Liposarcoma; Synovial Sarcoma; Metastatic Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Locally Advanced Sarcoma; Liposarcoma
MeSH terms: Sarcoma; Liposarcoma; Sarcoma, Synovial; Liposarcoma, Myxoid
Intervention: CMB305; atezolizumab
Intervention description: A combination of LV305 administered intradermally (ID) and G305 administered intramuscularly (IM); IV Infusion
Intervention MeSH terms: Atezolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 89.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: immunotherapy; CMB305; LV305; GLA-SE; atezolizumab; NY-ESO-1

Summary:

      This is an open-label Phase 2 randomized study that will examine the use of the study agents,
      CMB305 (sequentially administered LV305 which is a dendritic cell-targeting viral vector
      expressing the New York Esophageal Squamous Cell Carcinoma 1 gene [NY-ESO-1] and G305 which
      is a NY-ESO-1 recombinant protein plus glucopyranosyl lipid adjuvant-stable emulsion
      [GLA-SE]) in combination with atezolizumab or atezolizumab alone, in participants with
      locally advanced, relapsed or metastatic sarcoma (synovial or myxoid/round cell liposarcoma)
      expressing the NY-ESO-1 protein.

      There is no formal primary hypothesis for this study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Locally advanced, relapsed, or metastatic sarcoma with measurable tumor burden
             following therapy, as defined by Response Evaluation Criteria in Solid Tumors Version
             1.1 (RECIST 1.1); 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 immunohistochemistry (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

        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-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), anti-programmed cell death
             receptor 1 (PD-1), and anti-programmed cell death ligand (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 computed tomography (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 Chinese hamster ovary (CHO)
             cell products