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

Phase 1 Clinical Trial of a Personalized Cancer Vaccine (PCV) Strategy in Patients With Solid Tumors and Molecular Residual Disease

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.

Study Overview

• Status: Recruiting
• Conditions: Gastroesophageal Adenocarcinoma; Muscle-Invasive Bladder Carcinoma
• Intervention / Treatment: Biological: Synthetic long peptide personalized cancer vaccine; Drug: Poly ICLC; Device: Signatera assay

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Russell Pachynski, M.D.; Phone Number: 314-286-2341; Email: rkpachynski@wustl.edu
• Study Contact Backup: Name: William Gillanders, M.D.; Phone Number: 314-747-0072; Email: gillanders@wustl.edu

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Sub-Investigator: Joel Picus, M.D.
      • Sub-Investigator: Patrick Grierson, M.D.
      • Contact: William Gillanders, M.D.; Phone Number: 314-747-0072; Email: gillandersw@wustl.edu
      • Principal Investigator: William Gillanders, M.D.
      • Sub-Investigator: Robert Schreiber, Ph.D.
      • Sub-Investigator: Malachi Griffith, Ph.D.
      • Sub-Investigator: Feng Gao, M.D., Ph.D., MPH
      • Sub-Investigator: Peter Oppelt, M.D.
      • Sub-Investigator: Obi Griffith, Ph.D.
      • Sub-Investigator: Eric Knoche, M.D.
      • Sub-Investigator: Melissa Reimers, M.D.
      • Sub-Investigator: Ramon Jin, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria Cohort #1:

• 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
  • Creatinine clearance > 30 mL/min by Cockcroft-Gault
• The effects of synthetic long peptide personalized cancer vaccines and Hiltonol 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.
• No concurrent investigational therapies outside of this protocol are allowed.
• Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Exclusion Criteria Cohort #1:

• 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.
• 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.

Inclusion Criteria Cohort #2:

• Age ≥ 18 years.
• ECOG performance status ≤ 2 (Karnofsky ≥ 60%)
• Histologically confirmed gastroesophageal adenocarcinoma
• Stage II or III gastroesophageal adenocarcinoma (GEC).

• Complete surgical resection of GEC (R0). Full recovery from surgery and enrollment within 52 weeks following surgery with curative intent. 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:

  • Esophageal and Esophagogastric junction adenocarcinoma T1 N1-3 M0 or T2-4 N0-2M0.
  • Gastric adenocarcinoma T1-2 N1-3 M0 or T3-4 N0-3 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
  • Creatinine clearance > 30 mL/min by Cockcroft-Gault
• 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.
• No concurrent investigational therapies outside of this protocol are allowed.
• Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Exclusion Criteria Cohort #2:

• 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.
• 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 14 days of study entry.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Muscle Invasive Bladder Cancer (PCV); 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; Neoantigen vaccines will be provided on a patient-specific basis; Other Names: PCV; Drug: Poly ICLC; Poly-ICLC will be supplied by Oncovir, Inc.; Other Names: Hiltonol; Device: Signatera assay; 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
Experimental: Cohort 2: Gastroesophageal Adenocarcinoma (GEC); 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; Neoantigen vaccines will be provided on a patient-specific basis; Other Names: PCV; Drug: Poly ICLC; Poly-ICLC will be supplied by Oncovir, Inc.; Other Names: Hiltonol; Device: Signatera assay; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune response as measured by ELISPOT analysis	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)	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	Treatment screening, day 1, day 8, day 15, day 29, day 57, day 85, day 113, day 141, day 169, and during follow-up.	Through completion of follow-up (estimated to be 66 months)
Recurrence-free survival (RFS)	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.	Through completion of follow-up (estimated to be 66 months)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Natera, Inc.
• Investigators: Principal Investigator: William Gillanders, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2025
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): March 31, 2033

Study Registration Dates

• First Submitted: July 26, 2024
• First Submitted That Met QC Criteria: July 26, 2024
• First Posted (Actual): July 31, 2024

Study Record Updates

• Last Update Posted (Actual): January 13, 2026
• Last Update Submitted That Met QC Criteria: January 9, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Bladder cancer; Immunotherapy; Solid tumor; Gastroesophageal Adenocarcinoma; GEC; Personalized cancer vaccine
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urologic Neoplasms; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Immunologic Factors; Physiological Effects of Drugs; Interferon Inducers; poly ICLC
• Other Study ID Numbers: 202412028

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No