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

NCT05843448 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: UCDCC#290NCI-2023-02851P30CA093373
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 30 days after last dose

Secondary Outcomes (4)

• Complete response (CR)

  At 3 months

• Event-free survival

  At 18 months

• Cystectomy-free survival

  At 18 months

• Duration of response (DOR)

  Up to 3 years

Study Arms (1)

Treatment (IO102-IO103, pembrolizumab)

EXPERIMENTAL

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.

Biological: PD-L1/IDO Peptide Vaccine; Biological: Pembrolizumab

Interventions

PD-L1/IDO Peptide Vaccine BIOLOGICAL

Given SC

Also known as: IO102-IO103 Peptide Vaccine, IO103/IO102 Peptide Vaccine, PD-L1/IDO Peptide

Treatment (IO102-IO103, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (IO102-IO103, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Davis: lead
• IO Biotech: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Mamta Parikh

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Office of Clinical Research

CONTACT

916-382-6970; OCRReferral@health.ucdavis.edu

Study Design

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

Study Record Dates

• First Submitted: April 24, 2023
• First Posted: May 6, 2023
• Study Start: April 19, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 13, 2026

Record last verified: 2026-03

Locations

US (1)