Moffitt logo

Clinical Trials Search

Clinical Trial 19851

Cancer Type: Genitourinary
Interventions:Atezolizumab (Tecentriq); FPV-CV301; MVA-BN-CV301

Study Type: Treatment
Phase of Study: Phase II

  • Rohit Jain

Call 813-745-6100
or 1-800-679-0775

Study Title

A Phase 2, Multicenter, Single-Arm Trial of CV301 in Combination with PD-1/L1 Blockade in Patients with Locally Advanced or Metastatic Urothelial Bladder Cancer



Primary Objective: Objective Response Rate (ORR; Complete Response [CR] + Partial Response [PR] Rate) as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Secondary Objectives: Progression-Free Survival (PFS), Overall Survival (OS), Duration of Response, and Safety of the treatment combination of CV301 with atezolizumab. Exploratory Objectives: Analysis of biopsy tissue for differences between pre- and post-treatment samples correlation to patient survival e.g.: T cell receptor (TCR) clonality, Tumor-Infiltrating-Lymphocytes (TILs), Protein expression for e.g. Programmed Death Ligand 1 (PD-L1) and other biomarkers, Gene expression profiling for molecular subtyping, Tumor mutational burden; DNA damage response gene mutations, MSI status, MMR deficiency status, cell-free ctDNA. Analysis of peripheral blood mononuclear cells (PBMCs) / serum for differences between pre- and post-treatment samples correlation to patient survival e.g.: Antigen-specific immune responses to carcinoembryonic antigen (CEA) and mucin-1 (MUC-1) as well as to other tumor-associated antigens (TAAs) to assess antigen cascade, Immunophenotyping of immune cell subsets by flow cytometry, Soluble biomarkers (e.g. cytokines and classical tumor markers), TCR clonality, PD-1/L1 staining

Inclusion Criteria

  • Histologically or cytologically documented locally advanced or metastatic urothelial carcinoma
  • Participants with mixed histologies were required to have a dominant transitional cell pattern.
  • Locally advanced bladder cancer that was inoperable on the basis of involvement of the pelvic sidewall or adjacent viscera (clinical stage T4b) or bulky nodal metastasis (N2−N3).
  • Life expectancy ≥ 12 weeks.
  • Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions cannot be counted as target lesions unless there has been demonstrated progression in the lesion since radiotherapy and no other lesions are available for selection as target lesions.
  • Demonstrate adequate organ function.
  • For female participants of childbearing potential and male participants with partners of childbearing potential, agreement to use a highly effective form(s) of contraception and to continue its use for 5 months after the last dose of atezolizumab.
  • Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks preferred) or 10-15 unstained slides, with an associated pathology report.
  • For Cohort 1:
  • Untreated with chemotherapy
  • ECOG (Eastern Cooperative Oncology Group) performance status of 2, or Glomerular filtration rate calculated as creatinine clearance (Cockroft-Gault formula) of ≥20 mL/min and less than 60 mL/min or Hearing loss or neuropathy of any cause Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2
  • For Cohort 2:
  • Disease progression during or following treatment with at least one platinum-containing regimen (e.g., GC, MVAC, CarboGem, carboplatin-paclitaxel) for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence
  • ECOG (Eastern Cooperative Oncology Group) performance status of >Calculated creatinine clearance (Cockroft-Gault formula) of ≥20 mL/min

  • Exclusion Criteria

  • Any approved anti-cancer therapy, including chemotherapy, within 3 weeks prior to initiation of trial treatment
  • Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to screening
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).Participants with indwelling catheters (e.g., PleurX) are allowed
  • Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
  • Malignancies other than urothelial carcinoma within 3 years prior to Day 1, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or localized prostate cancer treated with curative intent and no intent for further treatment or incidental prostate cancer
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins, or aminoglycoside antibiotics or egg products, poxvirus-based vaccinations, or beef or bovine meat
  • Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
  • History of autoimmune disease. Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible for this trial or Participants with controlled Type I diabetes mellitus on a stable dose of insulin regimen are eligible for this trial
  • Participants with history of vitiligo and controlled psoriasis are eligible for the trial
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
  • Positive test for Human Immunodeficiency Virus (HIV)
  • Participants with active hepatitis B virus or hepatitis C virus (HCV)
  • Participants with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of HbsAg, negative polymerase chain reaction (PCR) for HBV) are eligible. HBV Deoxyribonucleic Acid (DNA) PCR must be obtained in these participants prior to Day 1
  • Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV Ribonucleic Acid (RNA) prior to enrollment
  • Active tuberculosis
  • Signs or symptoms clinically significant of infection within 2 weeks prior to Day 1
  • Received therapeutic oral or intravenous (IV) antibiotics within 1 week prior to Day 1
  • Participants receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible
  • Significant cardiovascular disease
  • Major surgical procedure other than for diagnosis within 28 days prior to Day 1 or anticipation of need for a major surgical procedure during the course of the trial
  • Prior allogeneic stem cell or solid organ transplant
  • Administration of a live, attenuated vaccine within 4 weeks before Day 1 or anticipation that such a live attenuated vaccine would be required during the trial
  • Influenza vaccination may be given during influenza season only). Participants cannot receive live, attenuated influenza vaccine (e.g., FluMist®) within 4 weeks prior to Day 1 or at any time during the trial
  • Refer to protocol for other exclusion criteria that may apply