Safety, Tolerability and Immunogenicity of a Personalized Neoantigen Cancer Vaccine Combined With Anti-PD-1 and Radiofrequency Ablation in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- iNeo-Vac-P01
- Conditions
- Advanced Malignant Solid Tumor
- Sponsor
- Sir Run Run Shaw Hospital
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- The IFN-γ T cells responses induced by neoantigen
- Status
- Recruiting
- Last Updated
- 5 years ago
Overview
Brief Summary
This research study is evaluating a new type of personalized neoantigen cancer vaccine（iNeo-Vac-P01）combined with anti-PD-1 antibody and radiofrequency ablation as a possible treatment for patients with advanced solid tumors. The primary objective of this trial is to evaluate safety, tolerability and immunogenicity of iNeo-Vac-P01 in combination with anti-PD-1 and radiofrequency ablation, so as to provide a new personalized therapeutic strategy for patients.
It is known that cancer patients have mutations (changes in genetic material) that are specific to an individual patient and tumor. These mutations can cause the tumor cells to produce proteins that appear very different from the body's own cells. It is possible that these proteins used in a vaccine may induce strong immune responses, which may help the participant's body fight any tumor cells that could cause the cancer to come back in the future. The study will examine the safety of the vaccine when given at several different time points and will examine the participant's blood cells for signs that the vaccine induced an immune response.
Investigators
Yong Fang
Chief Physician
Sir Run Run Shaw Hospital
Eligibility Criteria
Inclusion Criteria
- •Must freely sign informed consent;
- •Aged 18 to 75 years old;
- •Life expectancy of greater than 3 months.
- •At least one measurable lesion according to RECIST 1.1 criteria(Radiofrequency ablation of lesions was excluded).
- •histologically confirmed Advanced solid tumors,
- •have failed standard treatment, or unsuitable to receive standard treatment
- •Liver metastases are present and are suitable for radiofrequency ablation；
- •agreeable to allow tumor and normal samples to be submitted for complete exome and transcription sequencing.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
- •Good hematopoietic function ， defined as absolute neutrophils count ≥1.5×109 /L, platelet count ≥100 ×109 /L, and hemoglobin ≥90g/L；
Exclusion Criteria
- •Currently participating in an interventional clinical study treatment or has received other investigational drugs or used investigational devices within 4 weeks prior to the first administration;
- •Major surgical treatment within 3 weeks prior to first administration;
- •Completed palliative radiotherapy within 7 days prior to first administration;
- •Clinical active diverticulitis, abdominal abscess, and gastrointestinal obstruction;
- •Have none suitable neoantigen;
- •Have been bone marrow or stem cell transplants;
- •Clinically uncontrollable pleural effusion/peritoneal effusion/pericardial effusion;
- •Severe known allergic reactions (≥ grade 3) to the active ingredient and/or any excipient of PD-1 monoclonal antibody；
- •Active autoimmune disease requiring systemic treatment occurred within 2 years prior to initial administration；
- •Diagnosed with immunodeficiency or was receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dosing of the study；
Arms & Interventions
RFA+PD-1+iNeo-Vac-P01
Patients will undergo radiofrequency ablation. At Week 3, patients will receive PD-1 at a dose of 200mg administered by intravenous infusion (IV) every 2 weeks. At Week 12,all patients,regardless of their disease status,iNeo-Vac-P01(300mcg per peptide)+ GM-CSF (40mcg) on days 1, 4, 8, 15, 22, 52, and 82 from week 12. Additional booster vaccines might be administered depending on ethics and patients' potential benefit.
Intervention: iNeo-Vac-P01
RFA+PD-1+iNeo-Vac-P01
Patients will undergo radiofrequency ablation. At Week 3, patients will receive PD-1 at a dose of 200mg administered by intravenous infusion (IV) every 2 weeks. At Week 12,all patients,regardless of their disease status,iNeo-Vac-P01(300mcg per peptide)+ GM-CSF (40mcg) on days 1, 4, 8, 15, 22, 52, and 82 from week 12. Additional booster vaccines might be administered depending on ethics and patients' potential benefit.
Intervention: GM-CSF
RFA+PD-1+iNeo-Vac-P01
Patients will undergo radiofrequency ablation. At Week 3, patients will receive PD-1 at a dose of 200mg administered by intravenous infusion (IV) every 2 weeks. At Week 12,all patients,regardless of their disease status,iNeo-Vac-P01(300mcg per peptide)+ GM-CSF (40mcg) on days 1, 4, 8, 15, 22, 52, and 82 from week 12. Additional booster vaccines might be administered depending on ethics and patients' potential benefit.
Intervention: PD-1
RFA+PD-1+iNeo-Vac-P01
Patients will undergo radiofrequency ablation. At Week 3, patients will receive PD-1 at a dose of 200mg administered by intravenous infusion (IV) every 2 weeks. At Week 12,all patients,regardless of their disease status,iNeo-Vac-P01(300mcg per peptide)+ GM-CSF (40mcg) on days 1, 4, 8, 15, 22, 52, and 82 from week 12. Additional booster vaccines might be administered depending on ethics and patients' potential benefit.
Intervention: RFA
RFA+iNeo-Vac-P01+PD-1
Patients will undergo radiofrequency ablation. At Week 12, patients will receive iNeo-Vac-P01(300mcg per peptide)+ GM-CSF (40mcg) on days 1, 4, 8, 15, 22, 52, and 82 from week 12. Additional booster vaccines might be administered depending on ethics and patients' potential benefit. At Week 16, patients,regard of their disease status,will receive PD-1 at a dose of 200mg administered by intravenous infusion (IV) every 2 weeks.
Intervention: iNeo-Vac-P01
RFA+iNeo-Vac-P01+PD-1
Patients will undergo radiofrequency ablation. At Week 12, patients will receive iNeo-Vac-P01(300mcg per peptide)+ GM-CSF (40mcg) on days 1, 4, 8, 15, 22, 52, and 82 from week 12. Additional booster vaccines might be administered depending on ethics and patients' potential benefit. At Week 16, patients,regard of their disease status,will receive PD-1 at a dose of 200mg administered by intravenous infusion (IV) every 2 weeks.
Intervention: GM-CSF
RFA+iNeo-Vac-P01+PD-1
Patients will undergo radiofrequency ablation. At Week 12, patients will receive iNeo-Vac-P01(300mcg per peptide)+ GM-CSF (40mcg) on days 1, 4, 8, 15, 22, 52, and 82 from week 12. Additional booster vaccines might be administered depending on ethics and patients' potential benefit. At Week 16, patients,regard of their disease status,will receive PD-1 at a dose of 200mg administered by intravenous infusion (IV) every 2 weeks.
Intervention: PD-1
RFA+iNeo-Vac-P01+PD-1
Patients will undergo radiofrequency ablation. At Week 12, patients will receive iNeo-Vac-P01(300mcg per peptide)+ GM-CSF (40mcg) on days 1, 4, 8, 15, 22, 52, and 82 from week 12. Additional booster vaccines might be administered depending on ethics and patients' potential benefit. At Week 16, patients,regard of their disease status,will receive PD-1 at a dose of 200mg administered by intravenous infusion (IV) every 2 weeks.
Intervention: RFA
Outcomes
Primary Outcomes
The IFN-γ T cells responses induced by neoantigen
Time Frame: 2 years
The response of IFN-γ T cells induced by neoantigen was detected by ELispot.
Objective Response Rate
Time Frame: 5 years
ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study.
Number of participants experiencing clinical and laboratory adverse events (AEs)
Time Frame: 1 year
Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.
Measurement of CD4/CD8 T lymphocyte subsets.
Time Frame: 3 years
CD4/CD8 T lymphocyte subsets were detected by flow cytometry.
Secondary Outcomes
- Overall Survival(OS)(5 years)
- Peripheral blood T cell receptor sequencing analysis(2 years)
- Progression-free Survival(PFS)(3 years)