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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
1200 mg administered by IV infusion every 3 weeks (21 \[+/-2\] days) for up to 12 months in the adjuvant setting and up to 24 months in the metastatic setting.
PGV001: up to ten total doses of PGV001with helper peptides. The product is prepared within the ISMMS . The product consists of two independent preparations of patient specific long peptides mixed with poly-ICLC. A dose of PGV001 consists of the following: Up to ten synthetic peptides - 100μg (0.01 mL, 10 mg/mL) per peptide. One tetanus helper peptide - 100μg (0.01 mL, 10 mg/mL)
1.4 mg (0.7 mL, 2 mg/mL)
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Number of neoantigens
Feasibility parameter: Number of neoantigens identified per subject
Time frame: up to 24 months
Number of peptides synthesized
Feasibility parameter: Number of peptides synthesized per subject for vaccination
Time frame: up to 24 months
Vaccine Production time
Feasibility parameter:
Time frame: up to 24 months
Proportion of consent to tissue acquisition phase
Feasibility parameter: Proportion of subjects who consent to the tissue acquisition phase for whom a vaccine product is prepared
Time frame: up to 24 months
Proportion of subjects eligible for the treatment phase
Feasibility parameter: Proportion of subjects eligible for the treatment phase who complete the priming course of vaccination plus atezolizumab
Time frame: up to 24 months
Number of toxicities
Safety will be assessed by the frequency of toxicities as assessed by NCI-CTCAE 4.0 criteria
Time frame: up to 24 months
Objective Response Rate
Objective Response Rate by RECIST 1.1 . RECIST: complete response, partial response, stable disease, and progressive disease.
Time frame: up to 24 hours
Duration of response
The duration of response by RECIST 1.1 and immune-related RECIST criteria in patients with metastatic disease
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
0.19 mL
Time frame: up to 24 months
Time to Progression In Adjuvant patients
Time-to-progression in adjuvant patients using RECIST: complete response, partial response, stable disease, and progressive disease
Time frame: up to 24 months
Overall Survival
Number of participants living
Time frame: up to 24 months