A Phase Ib Trial of a Maintenance Multipeptide Vaccine (S-588210) in Patients With Unresectable Malignant Pleural Mesothelioma Without Progression After First-Line Chemotherapy
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Proportion of patients who show in vitro cytotoxic T lymphocyte induction to at least 2 of the 5 antigens determined by Enzyme-Linked ImmunoSpot (ELISPOT) assay
研究概览
简要总结
A phase Ib study investigating the safety, the immunogenicity and the optimal administration frequency of the S-588210 5-peptide vaccine in MPM patients without progression after pemetrexed-based chemotherapy will be conducted. Additionally, to identify more accurate predictive biomarkers of response to S-588210, T-cell-receptor-sequencing (TCR) pre- and post-vaccination will be performed in blood samples of patients treated with the vaccine. Immunohistochemical analysis of the vaccine oncoantigens will also be correlated with induction of antigen-specific T-cell responses. Finally, to explore the infiltration of tumors with T-cells and the potential presence of an immunosuppressive tumor microenvironment, immunohistochemistry for immune checkpoints (including PDL1/PD1, CTLA4) and immune suppressive cell subsets (T-regs, macrophages) will be performed.
详细描述
Primary Objective:
To evaluate the rate of peptide-specific CTL induction to S-588210 within the first 8 months in HLA-A*02:01-positive patients with MPM who have not progressed on first-line pemetrexed-based chemotherapy treated on a weekly or every other week vaccination schedule.
Secondary Objectives:
- To evaluate the safety of S-588210 in HLA-A*02:01-positive patients with MPM treated with S-588210
- To determine the disease control rate (DCR) in HLA-A*02:01-positive patients with MPM treated with S-588210
- To determine the progression-free-survival (PFS) in HLA-A*02:01-positive patients with MPM who have not progressed on first-line pemetrexed-based chemotherapy and who are treated with S-588210
- To evaluate the peptide-specific CTL response to S-588210 over time up to 8 months in HLA-A*02:01-positive patients with MPM who have not progressed on first-line pemetrexed-based chemotherapy
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with unresectable MPM that have completed 4-6 cycles of standard first-line pemetrexed-based chemotherapy for at least 1 month and have not progressed
- •Able to provide informed consent for the study
- •HLA-A*02:01 positive
- •ECOG PS=0-1 at enrollment
- •Measurable indicator lesion by modified RECIST criteria
- •Adequate bone marrow (ANC > 1000cells/ml, PLT > 50,000/ml, Hg > 8gr/dL), renal (Cr > 2.5xUNL) and liver function (AST, ALT< 3x UNL, total bilirubin < 2x UNL, ALP < 3x UNL)
- •Archival tumor tissue available for IHC (1 paraffin-embedded block)
- •Epithelioid or biphasic histology
排除标准
- •Chemotherapy or investigational antineoplastic drug within 1 month of planned initiation of vaccine therapy
- •Patients who received DEPDC1, MPHOSPH1, URLC10, CDCA1, or KOC1 peptide vaccines before
- •Active treatment with corticosteroids or other immunosuppressive agents
- •Patients who are expected to require any of the following therapies between enrollment and completion or discontinuation of the study treatment:
- •immunosuppressive drugs, including corticosteroids, methotrexate, mercaptopurine, azathioprine, cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, ATG (anti-thymoglobulin), IL2-receptor antibodies (basiliximab, daclizumab), TNF-a antibodies (infliximab, etanercept, adalimumab)
- •radiotherapy for the target disease
- •surgical therapy for the target disease
- •History of bone marrow transplantation
- •Active infection
- •Human immunodeficiency virus infection
- •History of or active systemic autoimmune disorder or immunodeficiency syndromes
- •History of severe (CTCAE v.4.03 grade 3 or higher) allergic reaction to a drug, vaccination, or biological preparation.
- •Pregnancy
- •Patients who cannot or do not intend to practice effective contraception
- •Severe illness requiring hospitalization
- •Lymphocytes <15% of total WBCs at baseline
- •Sarcomatoid histology
- •Severe (CTCAE v.4.03 grade 3 or higher) concurrent hepatic impairment, renal impairment, heart disease, hematological disease, respiratory disease, or metabolic disease
研究组 & 干预措施
Every other Week Vaccination
Maintenance multipeptide vaccine (S-588210) administered every other week
干预措施: Multipeptide vaccine S-588210 (Biological)
Weekly Vaccination
Maintenance multipeptide vaccine (S-588210) administered every week
干预措施: Multipeptide vaccine S-588210 (Biological)
结局指标
主要结局
Proportion of patients who show in vitro cytotoxic T lymphocyte induction to at least 2 of the 5 antigens determined by Enzyme-Linked ImmunoSpot (ELISPOT) assay
时间窗: Within 8 months from initiation of vaccination
次要结局
- 6-month progression-free survival (PFS) rate(6 months)
- Peptide-specific cytotoxic T lymphocyte response determined by Enzyme-Linked ImmunoSpot (ELISPOT) assay(At 2, 3, 4, 6 and 8 months of vaccination)
- Toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v4.03(Up to 4 weeks)
- Disease control rate defined as the proportion of patients who are assessed as having complete response (CR), partial response (PR), or stable disease (SD) (>3 months)(6 months)