RECRUITING

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

Conditions

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

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2023-04-19

Study Completion:2026-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05843448

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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

Inclusion Criteria

Exclusion 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

* 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

Contacts and Locations

Principal Investigator

Mamta Parikh

PRINCIPAL_INVESTIGATOR

University of California, Davis

Study Locations (Sites)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817

United States

Collaborators and Investigators

Sponsor: University of California, Davis

Mamta Parikh, PRINCIPAL_INVESTIGATOR, University of California, Davis

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-04-19

Study Completion Date2026-12

Study Record Updates

Study Start Date2023-04-19

Study Completion Date2026-12

Terms related to this study

Additional Relevant MeSH Terms

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