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

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ClinicalTrials.gov Identifier: NCT03359239
Recruitment Status : Not yet recruiting
First Posted : December 2, 2017
Last Update Posted : April 26, 2018
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Matthew Galsky, Icahn School of Medicine at Mount Sinai

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.

Condition or disease Intervention/treatment Phase
Urothelial/Bladder Cancer, Nos Drug: Atezolizumab Biological: PGV001 Drug: Poly ICLC Drug: Normal saline Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Atezolizumab Plus PGV001, a Multipeptide Personalized Neoantigen Vaccine, in Patients With Locally Advanced or Metad or Metastatic Urothelial Cancer
Estimated Study Start Date : July 1, 2018
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: Atezolizumab
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.
Other Name: TECENTRIQ

Biological: PGV001

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)


Drug: Poly ICLC
1.4 mg (0.7 mL, 2 mg/mL)

Drug: Normal saline
0.19 mL




Primary Outcome Measures :
  1. Number of neoantigens [ Time Frame: up to 24 months ]
    Feasibility parameter: Number of neoantigens identified per subject

  2. Number of peptides synthesized [ Time Frame: up to 24 months ]
    Feasibility parameter: Number of peptides synthesized per subject for vaccination

  3. Vaccine Production time [ Time Frame: up to 24 months ]
    Feasibility parameter:

  4. 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 with available vaccine at the time of otherwise meeting eligibility for the treatment phase

  5. 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

  6. 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


Secondary Outcome Measures :
  1. Objective Response Rate [ Time Frame: up to 24 hours ]
    Objective Response Rate by RECIST 1.1 . RECIST: complete response, partial response, stable disease, and progressive disease.

  2. Duration of response [ Time Frame: up to 24 months ]
    The duration of response by RECIST 1.1 and immune-related RECIST criteria in patients with metastatic disease

  3. Time to Progression In Adjuvant patients [ Time Frame: up to 24 months ]
    Time-to-progression in adjuvant patients using RECIST: complete response, partial response, stable disease, and progressive disease

  4. Overall Survival [ Time Frame: up to 24 months ]
    Number of participants living



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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) 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.

    • 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 mg/dL)
    • 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.

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.

  • 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.
  • Medication-Related Exclusion Criteria:

    • 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)
    • 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 transplantation

Please contact site for other inclusion/exclusion criteria.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03359239


Contacts
Contact: Suresh Ramanathan (212) 824-7372 suresh.ramanathan@mssm.edu

Locations
United States, New York
Icahn School of Medicine at Mount Sinai Not yet recruiting
New York, New York, United States, 10029
Sponsors and Collaborators
Matthew Galsky
Genentech, Inc.
Investigators
Principal Investigator: Matthew Galsky, MD Icahn School of Medicine at Mount Sinai

Responsible Party: Matthew Galsky, Professor, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT03359239     History of Changes
Other Study ID Numbers: GCO 16-1387
First Posted: December 2, 2017    Key Record Dates
Last Update Posted: April 26, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Matthew Galsky, Icahn School of Medicine at Mount Sinai:
PGV001
atezolizumab
urothelial cancer
personalized neoantigen vaccine

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Vaccines
Antibodies, Monoclonal
Poly ICLC
Atezolizumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Interferon Inducers