A Personalized Cancer Vaccine for the Treatment of Muscle-invasive Bladder Cancer in Patients with Molecular Residual Disease
This phase I trial studies the side effects of a personalized cancer vaccine (PCV) and tests how well it works in treating muscle-invasive bladder cancer (MIBC) in patients that have tumor cells in the body after complete surgical removal (molecular residual disease). A PCV includes up to 20 peptides as well as a dose of a drug called poly ICLC, which is a medication that improves the activity of the vaccine. A peptide is a naturally occurring biological molecule made up of amino acids. The PCV is designed to target mutations specific to each person’s tumor that are discovered during genetic testing of the tumor. Injection of the PCV may help the body build an effective immune response to kill more tumor cells.
Inclusion Criteria
- COHORT #1: Age ≥ 18 years
- COHORT #1: Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
- COHORT #1: Histologically confirmed muscle-invasive bladder cancer (MIBC) or upper tract urothelial carcinoma (renal pelvis and/or ureter)
- COHORT #1: Patients with carcinomas showing mixed histologies are required to have a dominant transitional cell pattern
- COHORT #1: Complete surgical resection of MIBC (R0) or upper tract urothelial carcinoma (renal pelvis and/or ureter).tumor, nodes, metastases (TNM) classification (based on the American Joint Committee on Cancer [AJCC] Cancer Staging Manual 8th ed.) at pathological examination of surgical resection specimen as follows: pT2-4aN0M0 or pT0-4aN+M0
- COHORT #1: Patient must have fully recovered from surgical resection in the opinion of the treating medical doctor (MD)
- COHORT #1: Circulating tumor deoxyribonucleic acid (ctDNA) positive result as identified by Signatera
- COHORT #1: Radiologic confirmation (by conventional imaging) of absence of residual disease and absence of metastasis
- COHORT #1: White blood cells (WBC) ≥ 1.5 K/cumm
- COHORT #1: Absolute neutrophil count ≥ 1.0 K/cumm
- COHORT #1: Platelets ≥ 50 K/cumm
- COHORT #1: Hemoglobin ≥ 8.0 g/dL
- COHORT #1: Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN)
- COHORT #1: Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) ≤ 3.0 x IULN
- COHORT #1: Creatinine clearance > 30 mL/min by Cockcroft-Gault
- COHORT #1: The effects of synthetic long peptide personalized cancer vaccines and Hiltonol and on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 5 months after completion of study interventions. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately
- COHORT #1: No concurrent investigational therapies outside of this protocol are allowed
- COHORT #1: Ability to understand and willingness to sign an institutional review board (IRB) approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
Exclusion Criteria
- Receiving any other investigational agents or planning to receive other investigational agents as part of neoadjuvant therapy. Patients who have received perioperative neoadjuvant chemotherapy and durvalumab are allowed
- Known allergy, or history of serious adverse reaction to vaccines such as anaphylaxis, hives, or respiratory difficulty
- A psychiatric illness or social situations that would limit compliance with study requirements as determined by the investigator from the medical history, physical exam, and/or medical record
- Prior or currently active autoimmune disease requiring management with immunosuppression. This includes inflammatory bowel disease, ulcerative colitis, Crohn’s disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, sarcoidosis, or other rheumatologic disease or any other medical condition or use of medication (e.g., corticosteroids) which might make it difficult for the patient to complete the full course of treatments or to generate an immune response to vaccines. In the case of asthma or chronic obstructive pulmonary disease taking inhaled corticosteroids that does not require daily systemic corticosteroids is acceptable. Additionally, local acting steroids (topical, inhaled, or intraarticular) will be allowed. Patients on intermittent or short course steroids will be allow if the dose does not exceed 4 mg of dexamethasone (or equivalent) per day for > 7 consecutive days. Premedication for chemotherapy does not apply to this criterion and may be administered as per standard of care (SOC) practice. Any patients receiving steroids should be discussed with the principal investigator (PI) to determine if eligible
- Pregnant and/or breastfeeding
- Known HIV-positive status
- History of positive test for hepatitis B virus surface antigen (HBsAg) and/or positive hepatitis C antibody result with detectable hepatitis C virus (HCV) ribonucleic acid (RNA) indicating acute or chronic infection
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia. For treatment enrollment the patient must have completed all prior cancer treatments > 28 days prior to vaccine administration with the exception of adjuvant SOC immunotherapy
- History of immuno-oncology treatment for MIBC in the neoadjuvant setting, with the following exceptions: * Treatment with adjuvant nivolumab as per current SOC * Receipt of perioperative neoadjuvant chemotherapy and durvalumab
- Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial per discussion with the PI
- Currently receiving any other investigational agents
- Live vaccine administered within 30 days prior to enrollment
- Immunodeficiency, systemic steroid therapy, or any other immunosuppressive therapy within 30 days of enrollment
- Active autoimmune disease (excluding diabetes mellitus and/or vitiligo), solid organ or allogeneic bone marrow transplant, or other known contraindications to receiving immunotherapy
- Severe hypersensitivity (grade ≥ 3) to checkpoint inhibitors and/or any of its excipients
- A psychiatric illness or social situations that would limit compliance with study requirements, as determined by the investigator from the medical history, physical exam, and/or medical record
- Current pneumonitis, a history of (non-infectious) pneumonitis requiring steroids, or history of clinically significant interstitial lung disease
- Active tuberculosis test within 3 months prior to treatment initiation
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum/urine pregnancy test within 7 days of study entry
Additional locations may be listed on ClinicalTrials.gov for NCT06529822.
Locations matching your search criteria
United States
Missouri
Saint Louis
PRIMARY OBJECTIVES:
I. Evaluate the safety of the synthetic long peptide personalized cancer vaccine strategy in patients with solid tumors and molecular residual disease.
II. Assess the feasibility of successful design and manufacture of a synthetic long peptide personalized cancer vaccine in patients with solid tumors and molecular residual disease.
SECONDARY OBJECTIVES:
I. Assess the immune response to the synthetic long peptide personalized cancer vaccines.
II. Assess the impact of the synthetic long peptide personalized cancer vaccines on molecular residual disease.
III. Evaluate the impact of the synthetic long peptide personalized cancer vaccines on the expression of cancer neoantigens.
TERTIARY/EXPLORATORY OBJECTIVES:
I. Assess the impact of the synthetic long peptide personalized cancer vaccines on the phenotype and function of neoantigen-specific T cells.
II. Assess the impact of the synthetic long peptide personalized cancer vaccines on the expression of cancer neoantigens.
OUTLINE:
Patients receive personalized synthetic long peptide vaccine (PCV) with poly-ICLC intramuscularly (IM) on days 1, 4, 8, 15, 29, 57, 85, 113, 141, and 169 in the absence of disease progression or unacceptable toxicity. Patients may also receive standard of care (SOC) nivolumab therapy at the discretion of the treating physician and according to institutional standards on study. Additionally, patients undergo blood sample collection and radiologic imaging throughout the study.
After completion of study treatment, patients are followed up at 28 days and then yearly for up to 5 years.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationSiteman Cancer Center at Washington University
Principal InvestigatorWilliam E. Gillanders
- Primary ID202412028
- Secondary IDsNCI-2025-00334
- ClinicalTrials.gov IDNCT06529822