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

NCT06529822 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: 202412028
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Muscle-Invasive Bladder Carcinoma; Gastroesophageal Adenocarcinoma

Keywords

Personalized cancer vaccine; Solid tumor; Immunotherapy; Bladder cancer; Gastroesophageal Adenocarcinoma; GEC

Outcome Measures

Primary Outcomes (6)

• 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)

  -At least possibly related to vaccine therapy

  From 1st vaccine dose through 30 days following last dose of vaccine (estimated to be 13 months)

• Safety as measured by serious adverse events (SAEs)

  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

  From 1st vaccine dose through 30 days following last dose of vaccine (estimated to be 13 months)

• Feasibility as measured by the success of enrolling patients with molecular residual disease

  The trial will be feasible if 8 patients with molecular residual disease are enrolled in 30 months

  Through 30 months

• Feasibility as measured by the expected time frame for vaccine creation

  The trial will be feasible if the vaccine is created within 24 weeks from signing of treatment consent to vaccine availability.

  Through 24 weeks

• Feasibility as measured by the rate of successful vaccine delivery

  The trial will be feasible if at least 50% of patients receive the vaccine

  Through 1st vaccine dose (estimated to be 24 weeks)

Secondary Outcomes (3)

• Immune response as measured by ELISPOT analysis

  Through 2 years after completion of treatment (estimated to be 2.5 years)

• Molecular residual disease as evaluated by ctDNA clearance using the Signatera assay

  Through completion of follow-up (estimated to be 66 months)

• Recurrence-free survival (RFS)

  Through completion of follow-up (estimated to be 66 months)

Study Arms (2)

Cohort 1: Muscle Invasive Bladder Cancer (PCV)

EXPERIMENTAL

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.

Biological: Synthetic long peptide personalized cancer vaccine; Drug: Poly ICLC; Device: Signatera assay

Cohort 2: Gastroesophageal Adenocarcinoma (GEC)

EXPERIMENTAL

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.

Biological: Synthetic long peptide personalized cancer vaccine; Drug: Poly ICLC; Device: Signatera assay

Interventions

Synthetic long peptide personalized cancer vaccine BIOLOGICAL

Neoantigen vaccines will be provided on a patient-specific basis

Also known as: PCV

Cohort 1: Muscle Invasive Bladder Cancer (PCV); Cohort 2: Gastroesophageal Adenocarcinoma (GEC)

Poly ICLC DRUG

Poly-ICLC will be supplied by Oncovir, Inc.

Also known as: Hiltonol

Cohort 1: Muscle Invasive Bladder Cancer (PCV); Cohort 2: Gastroesophageal Adenocarcinoma (GEC)

Signatera assay DEVICE

Signatera is a clinically validated, personalized, tumor-informed, multiplex-PCR and next-generation sequencing (NGS) based clinical trial assay targeting 16 tumor-specific mutations. It is intended for the detection of ctDNA isolated from anticoagulated peripheral whole blood from post-surgical patients previously diagnosed with localized or advanced solid tumors to aid physician assessment and treatment decision-making, together with other clinical factors

Cohort 1: Muscle Invasive Bladder Cancer (PCV); Cohort 2: Gastroesophageal Adenocarcinoma (GEC)

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years.
• ECOG performance status ≤ 2 (Karnofsky ≥ 60%).
• Histologically confirmed muscle-invasive bladder cancer (MIBC) or upper tract urothelial carcinoma (renal pelvis and/or ureter).
• Patients with carcinomas showing mixed histologies are required to have a dominant transitional cell pattern.
• 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.
• Patient must have fully recovered from surgical resection in the opinion of the treating MD.
• ctDNA positive result as identified by Signatera.
• Radiologic confirmation (by conventional imaging) of absence of residual disease and absence of metastasis.
• Adequate bone marrow and organ function as defined below:
• WBC ≥ 1.5 K/cumm
• Absolute neutrophil count ≥ 1.0 K/cumm
• Platelets ≥ 50 K/cumm
• Hemoglobin ≥ 8.0 g/dL
• Total bilirubin ≤ 1.5 x IULN
• AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN

You may not qualify if:

• 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 immunotherapy 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.
• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Natera, Inc.: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

poly ICLC

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

• William Gillanders, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

William Gillanders, M.D.

CONTACT

314-747-0072; gillanders@wustl.edu

Russell Pachynski, M.D.

CONTACT

314-286-2341; rkpachynski@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2024
• First Posted: July 31, 2024
• Study Start: March 20, 2025
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): March 31, 2033
• Last Updated: January 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)