Atezolizumab Given in Combination With a Personalized Vaccine in Patients With Urothelial Cancer

NCT03359239 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: GCO 16-1387
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Urothelial/Bladder Cancer, Nos

Keywords

PGV001; atezolizumab; urothelial cancer; personalized neoantigen vaccine

Outcome Measures

Primary Outcomes (6)

• Number of neoantigens

  Feasibility parameter: Number of neoantigens identified per subject

  up to 24 months

• Number of peptides synthesized

  Feasibility parameter: Number of peptides synthesized per subject for vaccination

  up to 24 months

• Vaccine Production time

  Feasibility parameter:

  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

  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

  up to 24 months

• Number of toxicities

  Safety will be assessed by the frequency of toxicities as assessed by NCI-CTCAE 4.0 criteria

  up to 24 months

Secondary Outcomes (4)

• Objective Response Rate

  up to 24 hours

• Duration of response

  up to 24 months

• Time to Progression In Adjuvant patients

  up to 24 months

• Overall Survival

  up to 24 months

Study Arms (1)

PGV 001 with Atezolizumab

EXPERIMENTAL

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.

Drug: Atezolizumab; Biological: PGV001; Drug: Poly ICLC; Drug: Normal saline

Interventions

Atezolizumab DRUG

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.

Also known as: TECENTRIQ

PGV 001 with Atezolizumab

PGV001 BIOLOGICAL

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)

PGV 001 with Atezolizumab

Poly ICLC DRUG

1.4 mg (0.7 mL, 2 mg/mL)

PGV 001 with Atezolizumab

Normal saline DRUG

0.19 mL

PGV 001 with Atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• History of HIV infection or active hepatitis B (chronic or acute) or hepatitis C infection
• Active tuberculosis
• A known additional primary malignancy that is progressing or requires active treatment. Exceptions include cancers that have undergone potentially curative therapy.
• Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway targeting agents
• No history of severe immune-related adverse effects from anti-CTLA 4 (NCI CTCAE Grade 3 and 4)

Sponsors & Collaborators

• Matthew Galsky: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (1)

• Saxena M, Anker JF, Kodysh J, O'Donnell T, Kaminska AM, Meseck M, Hapanowicz O, Niglio SA, Salazar AM, Shah HR, Kinoshita Y, Brody R, Rubinsteyn A, Sebra RP, Bhardwaj N, Galsky MD. Atezolizumab plus personalized neoantigen vaccination in urothelial cancer: a phase 1 trial. Nat Cancer. 2025 Jun;6(6):988-999. doi: 10.1038/s43018-025-00966-7. Epub 2025 May 9.

  PMID: 40346292 DERIVED

MeSH Terms

Conditions

Urologic Neoplasms

Interventions

atezolizumab; poly ICLC; Saline Solution

Condition Hierarchy (Ancestors)

Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Matthew Galsky, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 27, 2017
• First Posted: December 2, 2017
• Study Start: May 8, 2019
• Primary Completion: October 12, 2021
• Study Completion: October 12, 2021
• Last Updated: May 16, 2023

Record last verified: 2023-05

Locations

US (1)