Personalized Cancer Vaccine (PCV) Strategy in Patients With Solid Tumors and Molecular Residual Disease
NCT06529822 · Phase 1 · Orlando, Florida, United States
- Condition
- Bladder Cancer
- Disease stage
- Stage I-IV
- Phase
- Phase 1
- Study type
- BIOLOGICAL, DRUG, DEVICE
- Intervention
- Poly ICLC
- Age
- 18 Years to
- Gender
- All
- Sponsor
- Washington University School of Medicine
- Research institution
- Washington University School of Medicine
- Facility
- AdventHealth
- Research center
- AdventHealth
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.
Inclusion criteria
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: ypT0N0M0, pT2-4N0M0, 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, including enfortumab vedotin plus pembrolizumab (EV+P), 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. * Known HIV-positive status. * History of positive test for Hep
Primary outcomes
Safety as measured by treatment-emergent adverse events (TEAEs); Safety as measured by treatment-related adverse events (TRAEs); Safety as measured by serious adverse events (SAEs)
Secondary outcomes
Immune response as measured by ELISPOT analysis; Molecular residual disease as evaluated by ctDNA clearance using the Signatera assay; Recurrence-free survival (RFS)