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Clinical Trial 19851

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

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Rohit Jain

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

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

Summary

Objective

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 (T4b, any N M0; or any T, N 1−3 M0) or metastatic (M1, Stage IV; or metastatic recurrence after locoregional treatment) UC (including renal pelvis, ureters, urinary bladder, urethra). a. Patients with mixed histologies were required to have a dominant transitional cell pattern. b. 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).
  • Measurable disease, as defined by RECIST 1.1. 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.
  • Adequate organ function as defined by laboratory values per protocol. All screening labs should be performed within 14 days prior to the first trial product
  • Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks preferred) or at least ten 4μm and one 20μm unstained slides, with an associated pathology report. This specimen will be reviewed by a central reader but results of review will not be required prior to registration and treatment of the subject.
  • Inclusion for Cohort 1:
  • Untreated with chemotherapy for metastatic disease
  • Have at least one of the following: a. ECOG (Eastern Cooperative Oncology Group) performance status of 2, b. Glomerular filtration rate calculated as creatinine clearance (Cockroft-Gault formula) of ≥20 mL/min and less than 60 mL/min, c. Hearing loss or neuropathy of any cause Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2.
  • Inclusion 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, as defined per protocol.
  • 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 product; the following exceptions are allowed: a. Palliative radiotherapy for bone metastases or non-target soft tissue lesions completed > 7 days prior to baseline imaging. b. Hormone-replacement therapy or oral contraceptives.
  • Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to Day 1 (first dose of trial product) given that all AEs related to prior treatment have resolved to baseline or Grade 1.
  • Active central nervous system (CNS) metastases defined as computed tomography (CT) or magnetic resonance imaging (MRI) evidence of progression and prior radiographic assessments or Leptomeningeal disease.
  • Patients that have had prior diagnosis need to have stable disease by having results or performing CT/MRI with 1 month prior to 1st dose of treatment.
  • Uncontrolled tumor-related pain: a. Patients requiring pain medication must be on a stable regimen at trial entry. b. Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to trial entry. c. Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not currently associated with spinal cord compression) could be considered for loco-regional therapy if appropriate prior to first dose of trial product.
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). a. Patients with indwelling catheters (e.g., PleurX) are allowed.
  • Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or Ca > 12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab: a. Patients who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who did not have a history of clinically significant hypercalcemia are eligible. b. Patients who are receiving denosumab prior to first dose of trial product have to be willing and eligible to receive a bisphosphonate instead while in the trial.
  • 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 (T1/T2b, Gleason score ≤ 7 undergoing active surveillance and treatment naive).
  • Pregnant and lactating women.
  • 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, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, granulomatosis with polyangiitis, Sjogren¿s syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Some exceptions apply.
  • Additional exclusions apply