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IDO and PD-L1 Peptide Based Immune-Modulatory Therapeutic (IO102-IO103) in Combination With Pembrolizumab for BCG-Unresponsive or Intolerant, Non-Muscle Invasive Bladder Cancer

Primary Purpose

High Risk Non-Muscle Invasive Bladder Urothelial Carcinoma, Stage 0a Bladder Cancer AJCC v8, Stage 0is Bladder Cancer AJCC v8

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PD-L1/IDO Peptide Vaccine
Pembrolizumab
Sponsored by
University of California, Davis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for High Risk Non-Muscle Invasive Bladder Urothelial Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Adults >= 18 years of age Histologically confirmed high-risk NMIBC (T1, high-grade Ta, or carcinoma in situ [CIS]/Tis). Mixed histologies are allowed if predominantly transitional cell histology. Archival tissue or planned cystoscopy within 28 day of planned initiation of treatment Maximally resected tumor on study entry Cystectomy ineligible or declined Two induction courses of BCG attempted, regardless of exact doses received ECOG (Eastern Cooperative Oncology Group) performance status score of 0 - 2 Life expectancy >= 6 months Absolute neutrophil count (ANC) > 1000 cells/uL (=< 14 days of the first study treatment) Platelet count > 50,000/uL (=< 14 days of the first study treatment) Hemoglobin > 8 g/dL (=< 14 days of the first study treatment) Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 5 x upper limit of normal (ULN) (=< 14 days of the first study treatment) Alkaline phosphatase =< 5 x upper limit of normal (ULN) (=< 14 days of the first study treatment) Total bilirubin =< 2 x ULN (=< 14 days of the first study treatment) Creatinine clearance > 30 mL/min as measured using Cockcroft-Gault equation or the estimated glomerular filtration rate from the Modification of Diet in Renal Disease Study (=< 14 days of the first study treatment) International normalized ratio (INR) or activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless the subject is receiving anticoagulant therapy. Individuals on anticoagulant therapy should have a prothrombin time (PT) or partial thromboplastin time (PTT) within therapeutic range of intended use and no history of severe hemorrhage Ability to understand and willingness to sign an informed consent document Ability to adhere to the study visit schedule and other protocol requirements For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use methods of contraception Exclusion Criteria: Patients with a prior or concurrent malignancy whose natural history or treatment may, in the opinion of the investigator, have the potential to interfere with the safety or efficacy assessment of the investigational regimen Uncontrolled concomitant disease that in the opinion of the investigator would interfere with the patient's safety or compliance on trial Known history of positive test for human immunodeficiency virus (HIV) with CD4 < 200 or acquired immunodeficiency syndrome (AIDS)-defining condition Known active tuberculosis Active infection requiring systemic therapy, including active or intractable urinary tract infection (UTI) Previous treatment with checkpoint inhibitors targeting either PD-(L)1 or CTLA-4 Prior exposure to IO102 or IO103 Received systemic chemotherapy, targeted small molecule therapy, or radiotherapy =< 2 weeks before study treatment initiation Any adverse events from prior cancer therapy have resolved to grade =< 1 according to Common Terminology Criteria for Adverse Events (CTCAE) version 5 Congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to study entry or a history of myocarditis Any medical condition requiring systemic steroid equivalent to prednisone > 10 mg daily or immunosuppressive therapy within 14 days or 5 half-lives prior to first dose of trial therapy. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible. Patients who have adrenal insufficiency and hypophysitis from prior immunotherapy if they are on stable medical replacement doses are eligible Received a live or live-attenuated vaccine =< 30 days before the first dose of study treatment. Administration of killed vaccines, messenger ribonucleic acid (mRNA) based vaccines (e.g., COVID-19), and vector based vaccines are allowed Pregnant and/or breast feeding women. If a urine pregnancy test is positive or cannot be confirmed as negative, a serum pregnancy test will be required =< 24 hours prior to planned treatment initiation Evidence of active interstitial lung disease or history of non-infectious pneumonitis requiring systemic steroids Known allergy or reaction to any component of either study drug formulation Any condition that would prohibit the understanding or rendering of informed consent Any condition that in the opinion of the investigator would interfere with the patient's safety or compliance while on trial

Sites / Locations

  • University of California Davis Comprehensive Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (IO102-IO103, pembrolizumab)

Arm Description

Patients receive PD-L1/IDO peptide vaccine SC and pembrolizumab IV on study. Patients also undergo CT and/or CT/PET and collection of blood samples throughout the trial.

Outcomes

Primary Outcome Measures

Incidence of adverse events
Safety and toxicity will be evaluated according to Common Terminology Criteria for Adverse Events version 5.0 and pre-defined treatment-limiting toxicities.

Secondary Outcome Measures

Complete response (CR)
The CR rate will be estimated as the proportion of participants who experience an objective response, along with its exact 95% confidence interval. The CR rate at 3 months will be used to determine whether the trial will be expanded based on Simon's two-stage design.
Event-free survival
Kaplan-Meier methods will be used to estimate event-free (including recurrence on biopsy, development of muscle-invasive urothelial carcinoma, progression requiring radical cystectomy, or development of metastatic disease) survival at 18 months, along with 95% confidence intervals.
Cystectomy-free survival
Kaplan-Meier methods will also be used to estimate cystectomy-free survival at 18 months, along with 95% confidence intervals.
Duration of response (DOR)
DOR will be analyzed using Kaplan-Meier methods; medians and 95% confidence intervals will be computed.

Full Information

First Posted
April 24, 2023
Last Updated
July 6, 2023
Sponsor
University of California, Davis
Collaborators
IO Biotech, National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT05843448
Brief Title
IDO and PD-L1 Peptide Based Immune-Modulatory Therapeutic (IO102-IO103) in Combination With Pembrolizumab for BCG-Unresponsive or Intolerant, Non-Muscle Invasive Bladder Cancer
Official Title
Pilot Study of an IDO and PD-L1 Peptide Based Immune-Modulatory Therapeutic (IO102-IO103) in Combination With Pembrolizumab for BCG-Unresponsive or Intolerant, Non-Muscle Invasive Bladder Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 19, 2023 (Actual)
Primary Completion Date
June 2026 (Anticipated)
Study Completion Date
December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, Davis
Collaborators
IO Biotech, National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase I trial tests the safety and side effects of a PD-L1/IDO peptide vaccine (IO102-IO103) in combination with pembrolizumab in treating patients with non-muscle invasive bladder cancer. IO102-IO103 is a novel IDO and PD-L1 peptide based immune-modulatory therapeutic. It is designed to activate the patient's own immune cells (called T-cells) to fight the tumor and stop the tumor cells escaping from the body's immune system. IO102-IO103 works to directly kill tumor cells and remove the body's immune suppressive cells, which are cells that prevent the immune system from fighting the tumor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving IO102-IO103 in combination with pembrolizumab may make tumor cells more visible/recognizable to the immune system.
Detailed Description
PRIMARY OBJECTIVE: I. Evaluate the feasibility, safety and toxicity of the PD-L1/IDO peptide vaccine (IO102-IO103) in combination with pembrolizumab in patients with Bacillus Calmette-Guerin (BCG)-unresponsive or intolerant, non-muscle invasive bladder cancer (NMIBC). SECONDARY OBJECTIVES: I. To assess preliminary efficacy of IO102-IO103 in combination with pembrolizumab. II. To obtain preliminary efficacy of IO102-IO103 in combination with pembrolizumab. OUTLINE: Patients receive PD-L1/IDO peptide vaccine subcutaneously (SC) and pembrolizumab intravenously (IV) on study. Patients also undergo computed tomography (CT) and/or CT/positron emission tomography (PET) and collection of blood samples throughout the trial.After completion of study treatment, patients are followed up for 30 days and then every 3 months thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
High Risk Non-Muscle Invasive Bladder Urothelial Carcinoma, Stage 0a Bladder Cancer AJCC v8, Stage 0is Bladder Cancer AJCC v8, Stage I Bladder Cancer AJCC v8

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (IO102-IO103, pembrolizumab)
Arm Type
Experimental
Arm Description
Patients receive PD-L1/IDO peptide vaccine SC and pembrolizumab IV on study. Patients also undergo CT and/or CT/PET and collection of blood samples throughout the trial.
Intervention Type
Biological
Intervention Name(s)
PD-L1/IDO Peptide Vaccine
Other Intervention Name(s)
IO102-IO103 Peptide Vaccine, IO103/IO102 Peptide Vaccine, PD-L1/IDO Peptide
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda, Lambrolizumab, MK-3475, SCH 900475
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Incidence of adverse events
Description
Safety and toxicity will be evaluated according to Common Terminology Criteria for Adverse Events version 5.0 and pre-defined treatment-limiting toxicities.
Time Frame
Up to 30 days after last dose
Secondary Outcome Measure Information:
Title
Complete response (CR)
Description
The CR rate will be estimated as the proportion of participants who experience an objective response, along with its exact 95% confidence interval. The CR rate at 3 months will be used to determine whether the trial will be expanded based on Simon's two-stage design.
Time Frame
At 3 months
Title
Event-free survival
Description
Kaplan-Meier methods will be used to estimate event-free (including recurrence on biopsy, development of muscle-invasive urothelial carcinoma, progression requiring radical cystectomy, or development of metastatic disease) survival at 18 months, along with 95% confidence intervals.
Time Frame
At 18 months
Title
Cystectomy-free survival
Description
Kaplan-Meier methods will also be used to estimate cystectomy-free survival at 18 months, along with 95% confidence intervals.
Time Frame
At 18 months
Title
Duration of response (DOR)
Description
DOR will be analyzed using Kaplan-Meier methods; medians and 95% confidence intervals will be computed.
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adults >= 18 years of age Histologically confirmed high-risk NMIBC (T1, high-grade Ta, or carcinoma in situ [CIS]/Tis). Mixed histologies are allowed if predominantly transitional cell histology. Archival tissue or planned cystoscopy within 28 day of planned initiation of treatment Maximally resected tumor on study entry Cystectomy ineligible or declined Two induction courses of BCG attempted, regardless of exact doses received ECOG (Eastern Cooperative Oncology Group) performance status score of 0 - 2 Life expectancy >= 6 months Absolute neutrophil count (ANC) > 1000 cells/uL (=< 14 days of the first study treatment) Platelet count > 50,000/uL (=< 14 days of the first study treatment) Hemoglobin > 8 g/dL (=< 14 days of the first study treatment) Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 5 x upper limit of normal (ULN) (=< 14 days of the first study treatment) Alkaline phosphatase =< 5 x upper limit of normal (ULN) (=< 14 days of the first study treatment) Total bilirubin =< 2 x ULN (=< 14 days of the first study treatment) Creatinine clearance > 30 mL/min as measured using Cockcroft-Gault equation or the estimated glomerular filtration rate from the Modification of Diet in Renal Disease Study (=< 14 days of the first study treatment) International normalized ratio (INR) or activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless the subject is receiving anticoagulant therapy. Individuals on anticoagulant therapy should have a prothrombin time (PT) or partial thromboplastin time (PTT) within therapeutic range of intended use and no history of severe hemorrhage Ability to understand and willingness to sign an informed consent document Ability to adhere to the study visit schedule and other protocol requirements For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use methods of contraception Exclusion Criteria: Patients with a prior or concurrent malignancy whose natural history or treatment may, in the opinion of the investigator, have the potential to interfere with the safety or efficacy assessment of the investigational regimen Uncontrolled concomitant disease that in the opinion of the investigator would interfere with the patient's safety or compliance on trial Known history of positive test for human immunodeficiency virus (HIV) with CD4 < 200 or acquired immunodeficiency syndrome (AIDS)-defining condition Known active tuberculosis Active infection requiring systemic therapy, including active or intractable urinary tract infection (UTI) Previous treatment with checkpoint inhibitors targeting either PD-(L)1 or CTLA-4 Prior exposure to IO102 or IO103 Received systemic chemotherapy, targeted small molecule therapy, or radiotherapy =< 2 weeks before study treatment initiation Any adverse events from prior cancer therapy have resolved to grade =< 1 according to Common Terminology Criteria for Adverse Events (CTCAE) version 5 Congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to study entry or a history of myocarditis Any medical condition requiring systemic steroid equivalent to prednisone > 10 mg daily or immunosuppressive therapy within 14 days or 5 half-lives prior to first dose of trial therapy. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible. Patients who have adrenal insufficiency and hypophysitis from prior immunotherapy if they are on stable medical replacement doses are eligible Received a live or live-attenuated vaccine =< 30 days before the first dose of study treatment. Administration of killed vaccines, messenger ribonucleic acid (mRNA) based vaccines (e.g., COVID-19), and vector based vaccines are allowed Pregnant and/or breast feeding women. If a urine pregnancy test is positive or cannot be confirmed as negative, a serum pregnancy test will be required =< 24 hours prior to planned treatment initiation Evidence of active interstitial lung disease or history of non-infectious pneumonitis requiring systemic steroids Known allergy or reaction to any component of either study drug formulation Any condition that would prohibit the understanding or rendering of informed consent Any condition that in the opinion of the investigator would interfere with the patient's safety or compliance while on trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mamta Parikh
Organizational Affiliation
University of California, Davis
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California Davis Comprehensive Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mamta Parikh
Phone
916-734-5959
Email
mbparikh@ucdavis.edu
First Name & Middle Initial & Last Name & Degree
Mamta Parikh

12. IPD Sharing Statement

Learn more about this trial

IDO and PD-L1 Peptide Based Immune-Modulatory Therapeutic (IO102-IO103) in Combination With Pembrolizumab for BCG-Unresponsive or Intolerant, Non-Muscle Invasive Bladder Cancer

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