Personalized Cancer Vaccine (PCV) Strategy in Patients With Solid Tumors and Molecular Residual Disease

Phase 1

Recruiting

• Conditions: Muscle-Invasive Bladder Carcinoma
• Interventions: Biological: Synthetic long peptide personalized cancer vaccine; Drug: Poly ICLC; Device: Signatera assay

• Registration Number: NCT06529822
• Lead Sponsor: Washington University School of Medicine

Brief Summary

This is a phase 1 clinical trial to evaluate the safety, feasibility and immunogenicity of a personalized cancer vaccine strategy in patients with solid tumors and molecular residual disease. The hypothesis of the trial is that synthetic long peptide personalized cancer vaccines will be safe and capable of generating measurable neoantigen-specific T-cell responses enabling ctDNA clearance. The personalized cancer vaccines are composed of synthetic long peptides corresponding to prioritized cancer neoantigens and will be co-administered with poly-ICLC.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-07-26
• Study First Submitted QC: 2024-07-26
• Study First Posted: 2024-07-31
• Study Start: 2025-03-20
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-15
• Last Update Posted: 2025-09-19
• Primary Completion: 2028-10-31
• Study Completion: 2033-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

Not provided

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 SOC practice. Any patients receiving steroids should be discussed with the 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.

• Known allergy, or history of serious adverse reaction to vaccines such as anaphylaxis, hives, or respiratory difficulty.

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort 1: Muscle Invasive Bladder Cancer (PCV)	Synthetic long peptide personalized cancer vaccine	The schedule for vaccination will be Days 1, 4, 8, 15, 29, 57, 85, 113, 141, and 169. All study injections will be given intramuscularly and co-administered with poly-ICLC by a trained healthcare provider.
Cohort 1: Muscle Invasive Bladder Cancer (PCV)	Poly ICLC	The schedule for vaccination will be Days 1, 4, 8, 15, 29, 57, 85, 113, 141, and 169. All study injections will be given intramuscularly and co-administered with poly-ICLC by a trained healthcare provider.
Cohort 1: Muscle Invasive Bladder Cancer (PCV)	Signatera assay	The schedule for vaccination will be Days 1, 4, 8, 15, 29, 57, 85, 113, 141, and 169. All study injections will be given intramuscularly and co-administered with poly-ICLC by a trained healthcare provider.

Primary Outcome Measures

Name	Time	Method
Safety as measured by treatment-emergent adverse events (TEAEs)	From 1st vaccine dose through 30 days following last dose of vaccine (estimated to be 13 months)
Safety as measured by treatment-related adverse events (TRAEs)	From 1st vaccine dose through 30 days following last dose of vaccine (estimated to be 13 months)	-At least possibly related to vaccine therapy
Safety as measured by serious adverse events (SAEs)	From 1st vaccine dose through 30 days following last dose of vaccine (estimated to be 13 months)	As defined in 21 CFR 312.32: Definition: an adverse event is considered "serious" if, in the view of the investigator, it results in any of the following outcomes: * Death; * A life-threatening adverse event; * Inpatient hospitalization or prolongation of existing hospitalization; * A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; * A congenital anomaly/birth defect; * Any other important medical event that does not fit the criteria above but, based upon appropriate medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed above
Feasibility as measured by the success of enrolling patients with molecular residual disease	Through 30 months	The trial will be feasible if 8 patients with molecular residual disease are enrolled in 30 months
Feasibility as measured by the expected time frame for vaccine design and manufacture	Through 24 weeks	The trial will be feasible if the vaccine is designed and manufactured within 24 weeks.
Feasibility as measured by the rate of successful vaccine delivery	Through 1st vaccine dose (estimated to be 24 weeks)	The trial will be feasible if at least 50% of patients receive the vaccine

Secondary Outcome Measures

Name	Time	Method
Immune response as measured by ELISPOT analysis	Through 2 years after completion of treatment (estimated to be 2.5 years)	Treatment screening, day 1, day 15, day 29, day 57, day 85, day 113, day 141, day 169, 1 year (optional), and 2 years (optional)
Molecular residual disease as evaluated by ctDNA clearance using the Signatera assay	Through completion of follow-up (estimated to be 66 months)	Treatment screening, day 1, day 8, day 15, day 29, day 57, day 85, day 113, day 141, day 169, and during follow-up.
Recurrence-free survival (RFS)	Through completion of follow-up (estimated to be 66 months)	Recurrence-free survival is defined as the rate of recurrence from treatment enrollment until disease recurrence per standard of care assessments, or until patient is off study, whichever occurs first.

Trial Locations

Locations (1)

Washington University School of Medicine; 🇺🇸 St Louis, Missouri, United States