This is a single arm, proof-of-concept study. Fifteen subjects with urothelial cancer
interested in participation will sign a "tissue acquisition and vaccine preparation consent"
after which tumor tissue will be obtained from either a surgical resection specimen or
biopsy. Subjects are scheduled to undergo cystectomy or nephroureterectomy for invasive
urothelial cancer may consent prior to, or within 6 weeks after, surgery. The tumor specimen
will be submitted for genomic sequencing followed by neoantigen identification utilizing a
computational pipeline. Peptides corresponding to these neoantigens will be prepared for the
personalized vaccine product. Subjects eligible for the treatment phase of the protocol
(i.e., after surgery in adjuvant patients and chemotherapy in metastatic patients) will
receive atezolizumab every 3 weeks plus up to ten doses of PGV001 vaccination plus Poly-ICLC.
The primary objectives will be to determine the feasibility and safety of administration of a
personalized neoantigen-based vaccine (PGV001) plus atezolizumab in subjects with locally
advanced or metastatic urothelial cancer.
- Written informed consent and HIPAA authorization for release of personal health
- Age ≥ 18 years at the time of consent.
- ECOG Performance Status of ≤ 1 within fourteen days of registration for protocol
- Histological or cytological evidence of urothelial cancer of the bladder, urethra,
ureter, or renal pelvis. Differentiation with variant histologies (e.g., squamous cell
differentiated) will be permitted provided that the predominant histology is
- Clinical disease state specific criteria:
- Subjects with invasive urothelial cancer of the bladder or upper urinary tract
may consent either before or within 6 weeks after radical cystectomy or
- Subjects with metastatic and/or unresectable disease must have a metastatic site
amenable to biopsy. In situations where a metastatic biopsy does not yield
sufficient genetic material for sequencing, or a biopsy cannot be feasibly
performed, the use of archival tumor tissue may be considered on a case by case
basis. The archival tissue must be derived from a muscle-invasive urothelial
cancer specimen or metastatic urothelial cancer specimen.
- Required laboratory values must be obtained within thirty days of consent.
- ANC ≥ 1500 cells/µL
- WBC counts > 2500/µL
- Lymphocyte count ≥ 300/µL
- Platelet count ≥ 100,000/µL
- Hemoglobin ≥ 8.0 g/dL
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN) with the following exception:
o Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN
may be enrolled.
- AST and ALT ≤ 3.0 x ULN with the following exception:
o Patients with liver involvement: AST and/or ALT ≤ 5 x ULN
- Alkaline phosphatase ≤ 2.5 x ULN with the following exception:
o Patients with documented liver involvement or bone metastases: alkaline
phosphatase ≤ 5 x ULN
- Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 30 mL/min on the basis of
the Cockcroft-Gault glomerular filtration rate estimation:
- (140 - age) x (weight in kg) x (0.85 if female) / 72 x (serum creatinine in
- INR and aPTT ≤ 1.5 x ULN o This applies only to patients who do not receive
therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such
as low-molecular-weight heparin or warfarin) should be on a stable dose.
- Known clinically significant liver disease, including active viral, alcoholic, or
other hepatitis; cirrhosis; fatty liver; and inherited liver disease
- Symptomatic CNS metastases and/or metastases to brain stem, midbrain, pons, medulla,
cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm) and/or
history of intracranial hemorrhage or spinal cord hemorrhage
- Pregnancy, lactation, or breastfeeding
- Known hypersensitivity to Chinese hamster ovary cell products or other recombinant
- History or risk of autoimmune disease, including but not limited to systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's
syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune
thyroid disease, vasculitis, or glomerulonephritis
- Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid
replacement hormone may be eligible.
- Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be
- Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis would be
excluded) are permitted provided that they meet the following conditions:
- History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
pneumonia, etc.), or evidence of active pneumonitis on screening chest computed
tomography (CT) scan
o History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- History of HIV infection or active hepatitis B (chronic or acute) or hepatitis C
- Active tuberculosis
- A known additional primary malignancy that is progressing or requires active
treatment. Exceptions include cancers that have undergone potentially curative
- Medication-Related Exclusion Criteria:
- Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway
- No history of severe immune-related adverse effects from anti-CTLA 4 (NCI CTCAE
Grade 3 and 4)
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins
- Patients with prior allogeneic bone marrow transplantation or prior solid organ
Please contact site for other inclusion/exclusion criteria.