Pilot Study of Atezolizumab Plus PGV001, a Multipeptide Personalized Neoantigen Vaccine, in Patients With Locally Advanced or Metad or Metastatic Urothelial Cancer
Overview
- Phase
- Phase 1
- Intervention
- Atezolizumab
- Conditions
- Urothelial/Bladder Cancer, Nos
- Sponsor
- Matthew Galsky
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Number of neoantigens
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
The purpose of this study is to determine the good and bad effects of atezolizumab given in combination with a personalized cancer vaccine in patients with urothelial cancer either after surgery to remove organ where the tumor arose (for example, removal of the bladder) or for urothelial cancer that has spread to other organs.
Detailed Description
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.
Investigators
Matthew Galsky
Professor
Icahn School of Medicine at Mount Sinai
Eligibility Criteria
Inclusion Criteria
- •Written informed consent and HIPAA authorization for release of personal health information.
- •Age ≥ 18 years at the time of consent.
- •ECOG Performance Status of ≤ 1 within fourteen days of registration for protocol therapy.
- •Histological or cytological evidence of urothelial cancer of the bladder, urethra, ureter, or renal pelvis. Differentiation with variant histologies (e.g., squamous cell differentiated) or pure variant histologies will be permitted provided that the predominant histology is urothelial carcinoma.
- •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 nephroureterectomy.
- •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
Exclusion Criteria
- •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 human antibodies
- •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 eligible.
- •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.
Arms & Interventions
PGV 001 with Atezolizumab
Atezolizumab: programmed death-ligand 1 PGV001:personalized cancer vaccine PGV 001 - vaccine Poly ICLC- adjuvant The product is prepared within the Icahn School of Medicine at Mount Sinai (ISMMS) . The product consists of two independent preparations of patient specific long peptides mixed with poly-ICLC.
Intervention: Atezolizumab
PGV 001 with Atezolizumab
Atezolizumab: programmed death-ligand 1 PGV001:personalized cancer vaccine PGV 001 - vaccine Poly ICLC- adjuvant The product is prepared within the Icahn School of Medicine at Mount Sinai (ISMMS) . The product consists of two independent preparations of patient specific long peptides mixed with poly-ICLC.
Intervention: PGV001
PGV 001 with Atezolizumab
Atezolizumab: programmed death-ligand 1 PGV001:personalized cancer vaccine PGV 001 - vaccine Poly ICLC- adjuvant The product is prepared within the Icahn School of Medicine at Mount Sinai (ISMMS) . The product consists of two independent preparations of patient specific long peptides mixed with poly-ICLC.
Intervention: Poly ICLC
PGV 001 with Atezolizumab
Atezolizumab: programmed death-ligand 1 PGV001:personalized cancer vaccine PGV 001 - vaccine Poly ICLC- adjuvant The product is prepared within the Icahn School of Medicine at Mount Sinai (ISMMS) . The product consists of two independent preparations of patient specific long peptides mixed with poly-ICLC.
Intervention: Normal saline
Outcomes
Primary Outcomes
Number of neoantigens
Time Frame: up to 24 months
Feasibility parameter: Number of neoantigens identified per subject
Vaccine Production time
Time Frame: up to 24 months
Feasibility parameter:
Proportion of subjects eligible for the treatment phase
Time Frame: up to 24 months
Feasibility parameter: Proportion of subjects eligible for the treatment phase who complete the priming course of vaccination plus atezolizumab
Number of toxicities
Time Frame: up to 24 months
Safety will be assessed by the frequency of toxicities as assessed by NCI-CTCAE 4.0 criteria
Number of peptides synthesized
Time Frame: up to 24 months
Feasibility parameter: Number of peptides synthesized per subject for vaccination
Proportion of consent to tissue acquisition phase
Time Frame: up to 24 months
Feasibility parameter: Proportion of subjects who consent to the tissue acquisition phase for whom a vaccine product is prepared
Secondary Outcomes
- Duration of response(up to 24 months)
- Objective Response Rate(up to 24 hours)
- Time to Progression In Adjuvant patients(up to 24 months)
- Overall Survival(up to 24 months)