Personalized Cancer Vaccine (PCV) Strategy in Patients With Solid Tumors and Molecular Residual Disease
- Conditions
- Interventions
- 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 res...
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 16
- Age ≥ 18 years.
- Histologically confirmed muscle-invasive bladder cancer (MIBC).
- Patients with carcinomas showing mixed histologies are required to have a dominant translational cell pattern.
- 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
- Availability of a ctDNA report that is based on tumor tissue specimen and matched blood.
- Radiologic confirmation (by conventional imaging) of absence of residual disease and absence of metastasis no more than 28 days prior to enrollment.
- 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.
Step 0
- Receiving any other investigational agents, or planning to receive other investigational agents as part of neoadjuvant therapy.
- Known allergy, or history of serious adverse reaction to vaccines such as anaphylaxis, hives, or respiratory difficulty.
- Acute or chronic, clinically significant hematologic, pulmonary, cardiovascular, hepatic renal, and/or other functional abnormality that might jeopardize the health and safety of the participant as determined by the investigator based on medical history, physical examination, laboratory values, and/or diagnostic studies. If needed and appropriate. the final determination related to study eligibility prior to the administration of the first vaccine will be documented by both the PI and Sub-Investigators in consultation with a specialist.
- 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.
Step 1 Inclusion Criteria:
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ctDNA positive result as identified by Signatera.
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ECOG performance status ≤ 1 (Karnofsky ≥ 60%).
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Complete surgical resection of MIBC (R0).
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Full recovery from cystectomy and enrollment within 52 weeks following cystectomy.
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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
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The effects of synthetic long peptide personalized cancer vaccines, Hiltonol and nivolumab 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 and/or SOC nivolumab therapy. 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.
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Women of childbearing potential and men must agree to use two forms of adequate contraception prior to study entry, for the duration of study participation, and for 3 months after completion of the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
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It is anticipated that patients will be treated with adjuvant nivolumab therapy during personalized vaccine therapy. Of note, adjuvant nivolumab therapy is considered standard of care in this patient population. No concurrent investigational therapies outside of this protocol are allowed.
Step 1 Exclusion Criteria:
- 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 Step 1 Enrollment the patient must have completed all prior cancer treatments > 28 days prior to vaccine administration with the exception of adjuvant nivolumab. No concurrent investigational therapies allowed.
- History of immuno-oncology treatment for MIBC in the neoadjuvant setting. (It is anticipated that patients will be treated with adjuvant nivolumab as per current SOC and this is allowed).
- 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.
- Acute or chronic, clinically significant hematologic, pulmonary, cardiovascular, hepatic renal, and/or other functional abnormality that might jeopardize the health and safety of the participant as determined by the investigator based on medical history, physical examination, laboratory values, and/or diagnostic studies. If needed and appropriate. the final determination related to study eligibility prior to the administration of the first vaccine will be documented by both the PI and Sub-Investigators in consultation with a specialist.
- 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 & 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. It is anticipated that the PCV will be administered concurrently with nivolumab in patients enrolled in Cohort #1 Muscle Invasive Bladder Cancer. Adjuvant nivolumab is considered standard of care in this patient population. Concurrent administration with adjuvant nivolumab is anticipated but not required. Cohort 1: Muscle Invasive Bladder Cancer (PCV) Nivolumab 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. It is anticipated that the PCV will be administered concurrently with nivolumab in patients enrolled in Cohort #1 Muscle Invasive Bladder Cancer. Adjuvant nivolumab is considered standard of care in this patient population. Concurrent administration with adjuvant nivolumab is anticipated but not required. 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. It is anticipated that the PCV will be administered concurrently with nivolumab in patients enrolled in Cohort #1 Muscle Invasive Bladder Cancer. Adjuvant nivolumab is considered standard of care in this patient population. Concurrent administration with adjuvant nivolumab is anticipated but not required. 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. It is anticipated that the PCV will be administered concurrently with nivolumab in patients enrolled in Cohort #1 Muscle Invasive Bladder Cancer. Adjuvant nivolumab is considered standard of care in this patient population. Concurrent administration with adjuvant nivolumab is anticipated but not required.
- Primary Outcome Measures
Name Time Method Safety as measured by treatment-related adverse events (TRAEs) From step 1 enrollment through 30 days following last dose of vaccine (estimated to be 13 months) -At least possibly related to vaccine therapy
Safety as measured by treatment-emergent adverse events (TEAEs) From step 1 enrollment through 30 days following last dose of vaccine (estimated to be 13 months) Safety as measured by serious adverse events (SAEs) From step 1 enrollment 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
...Feasibility as measured by the success of enrolling patients with molecular residual disease Through 30 months The trial will be feasible if 16 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 3 years) Step 0 enrollment, Step 1 enrollment, 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 Signaterra assay Through completion of follow-up (estimated to be 78 months) Step 1, 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 78 months) Recurrence-free survival is defined as the rate of recurrence from Step 1 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
🇺🇸Saint Louis, Missouri, United States