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.
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.
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.
Parallel
Synthetic long peptide personalized cancer vaccine
Biological/VaccineNeoantigen vaccines will be provided on a patient-specific basis
Poly ICLC
DrugPoly-ICLC will be supplied by Oncovir, Inc.
Signatera or Altera testing
DeviceTesting used to identify and prioritize neoantigens.
Safety as measured by treatment-emergent adverse events (TEAEs)
Safety as measured by treatment-related adverse events (TRAEs)
-At least possibly related to vaccine therapy
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
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
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)
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.
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.
Click on the lead sponsor to view all of their trials.
Washington University School of Medicine
Lead sponsor
Natera, Inc.
Collaborator
