Multi-peptide Vaccination and Bispecific PSMAxCD3 Antibody Treatment in Patients With Prostate Cancer (ImmProCure)
Randomized Phase II Study of Multi-peptide Vaccination and Bispecific PSMAxCD3 Antibody Treatment in Patients With Biochemical Relapse of Prostate Cancer
This trial is a phase II, randomized, open label study designed to evaluate safety, tolerability and efficacy of CC-1, a bispecific antibody (bsAb) with PSMAxCD3 specificity, and of VACXS15-PC01, a prostate cancer (PC)-specific multi-peptide vaccine, both administered as single agent or in combination to patients affected with biochemical recurrence (BCR) of PC after local therapy with curative intent. Patients will not receive other treatments during trial participation.
研究概览
详细说明
CC-1 contains a PSMA binder with particular reactivity in PC and also binds to tumor vessels, thereby allowing for a dual mode of anti-cancer action. CC-1 was developed in a novel format which not only prolongs serum half-life, but most importantly reduces off-target T cell activation with expected fewer side effects. The multi-peptide vaccine VAC-XS15-PC01 is composed of 10 HLA-restricted antigens, comprising immunopeptidome-defined PC-associated epitopes, adjuvanted with the TLR1/2 ligand XS15 emulsified in Montanide ISA 51 VG.
The study entails three-arms: (1) the multi-peptide vaccine VAC-XS15-PC01 alone, (2) PSMAxCD3 bispecific antibody CC-1 alone and (3) combinatorial treatment of CC-1 and VAC-XS15-PC01. Up to 84 patients are recruited (n = up to 28 per arm) and patients are randomly assigned 1:1:1 (drop-out rate of 15% anticipated). A translational research program comprising, among others, a strict evaluation of prostate specific antigen (PSA) course integrated with analysis of CC-1 induced immune response and immunogenicity of VAC-XS15-PC01 serves to detect early signs of efficacy. Furthermore, safety of the investigational medical products is evaluated, and tolerability of their combination are assessed.
研究类型
注册 (估计的)
阶段
- 阶段2
联系人和位置
学习联系方式
- 姓名：Susanne Jung, Dr. med.
- 电话号码：+49 (0)7071-29 83275
- 邮箱：kketi@med.uni-tuebingen.de
学习地点
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Baden-Wurttemberg
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Heidelberg、Baden-Wurttemberg、德国、69120
- 尚未招聘
- NCT Studienzentrale; Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg
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接触：
- Stefanie Zschaebitz, Dr. med.
- 电话号码：+49 (0)6221-56-35950
- 邮箱：kketi@med.uni-tuebingen.de
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Tübingen、Baden-Wurttemberg、德国、72076
- 招聘中
- CCU Transltional Immunolgy, University Hospital Tübingen
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接触：
- Susanne Jung, Dr. med.
- 电话号码：+49 (0)7071-29 83275
- 邮箱：kketi@med.uni-tuebingen.de
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Beriln
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Berlin、Beriln、德国、12203
- 尚未招聘
- Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin - Studienzentrale Onkologie
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接触：
- Sebastian Ochsenreither, Prof. Dr.
- 电话号码：+49 30 450 613 483
- 邮箱：kketi@med.uni-tuebingen.de
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North Rhine-Westphalia
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Essen、North Rhine-Westphalia、德国、45147
- 尚未招聘
- Universitätsklinikum Essen, Abteilung Urologie
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接触：
- Darr Christopher, Dr. med.
- 电话号码：+49 (0)201 723-3210
- 邮箱：kketi@med.uni-tuebingen.de
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
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Understand and voluntarily sign an IC document prior to any study related assessments/procedures
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Understand and voluntarily sign an IC document prior to any study related assessments/procedures
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Patient is able to understand and comply with the protocol for the duration of the study including treatment and scheduled visits and examinations
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Men aged ≥ 18 and ≤80 years
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Histologic diagnosis of prostatic adenocarcinoma
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Biochemical recurrence (BCR): PSA recurrence after treatment with curative intent; PSA ≥0.2 ng/mL or PSA > nadir + 2 ng/mL (after definitive RT), with two increasing PSA values prior to study treatment; AND no distant metastasis upon PSMA-PET imaging
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Patients are ineligible to receive available treatment alternatives
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Low risk of rapid disease progression, defined as:
o PSA-DT > 1 year AND pathological ISUP grade < 4 for men with prior RP OR Interval to BCR > 18 months AND biopsy ISUP grade < 4 for men with prior radiation therapy
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In case of second relapse PSA-DT > 9 months
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Eastern Cooperative Oncology Group (ECOG) performance status ≤1
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Exclusion Criteria:
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• PSA >5 ng/mL (at screening)
- Patients who are receiving or have previously received androgen deprivation treatment.
Except testosterone has recovered to normal levels: patients who have previously received anti-hormonal treatment testosterone must be >12 nmol/l.
- Patients who are planned to or are undergoing salvage therapy (e.g. radiation)
- Clinically significant xerostomia (dry mouth >1grade according to CTCAE v6.0)
- Untreated current or prior distant metastasis of PC
- Other malignancy within the last 2 years except: adequately treated non-melanoma skin cancer and non-muscle invasive bladder cancer.
- Concurrent or previous treatment within 30 days in another interventional clinical trial with an investigational anti-cancer therapy
- Clinical signs of active infection (> grade 2 according to CTCAE v6.0)
- History of HIV infection
- Viral active or chronic hepatitis (HBV or HCV)
- Autoimmune disease that requires or has required treatment with systemic immunosuppressive treatments, except low dose corticosteroids (< 10 mg/ day), in the past 1 year
- Ongoing relevant CNS pathology (e.g. seizure, paresis, aphasia, cerebrovascular ischemia, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder)
- Epilepsy requiring pharmacologic treatment
- Major surgery within 4 weeks of starting study treatment. Patients must have recovered from any effects of major surgery.
- Heart failure NYHA III/IV
- Severe obstructive or restrictive ventilation disorder
- Known intolerance to CC-1, or other immunoglobulin drug products as well as hypersensitivity to any of the excipients present in the respective drug products (CC-1, VAC-XS15-PC01)
- Refrain from blood donation during the course of the study
- Male patients have to refrain from sperm donations for 6 months after last IMP
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
有源比较器：Multi-peptide vaccine VAC-XS15-PC01
The vaccine VAC-XS15-PC01 consists of 300 µg of each of 10 PC-associated peptides. The vaccine cocktail (final volume 500 µL) will be administered subcutaneously (SC), adjuvanted with the TLR1/2 ligand XS15 (50 µg) and emulsified in Montanide ISA 51 VG at a 1:1 ratio. A total of three vaccinations are planned in Arm 1, administered 4 weeks apart from each other. |
The vaccine VAC-XS15-PC01 consists of 300 µg of each of 10 PC-associated peptides. The vaccine cocktail (final volume 500 µL) will be administered subcutaneously (SC), adjuvanted with the TLR1/2 ligand XS15 (50 µg) and emulsified in Montanide ISA 51 VG at a 1:1 ratio. A total of three vaccinations are planned in Arm 1, administered 4 weeks apart from each other. |
|
有源比较器：PSMAxCD3 bispecific antibody CC-1
CC-1 is applied subcutaneously once per week for 12 weeks in Arm 2. Due to priming doses up to 14 applications are planned. |
CC-1 is applied subcutaneously once per week for 12 weeks in Arm 2. Due to priming doses up to 14 applications are planned. |
|
实验性的：PSMAxCD3 bispecific antibody CC-1 + Multi-peptide vaccine VAC-XS15-PC01
The vaccine VAC-XS15-PC01 consists of 300 µg of each of 10 PC-associated peptides. The vaccine cocktail (final volume 500 µL) will be administered subcutaneously (SC), adjuvanted with the TLR1/2 ligand XS15 (50 µg) and emulsified in Montanide ISA 51 VG at a 1:1 ratio. A total of three vaccinations are planned in Arm 3, administered 4 weeks apart from each other. CC-1 is applied subcutaneously once per week for 12 weeks in Arm 3. Due to priming doses up to 14 applications are planned. |
The vaccine VAC-XS15-PC01 consists of 300 µg of each of 10 PC-associated peptides. The vaccine cocktail (final volume 500 µL) will be administered subcutaneously (SC), adjuvanted with the TLR1/2 ligand XS15 (50 µg) and emulsified in Montanide ISA 51 VG at a 1:1 ratio. A total of three vaccinations are planned in Arm 1, administered 4 weeks apart from each other. CC-1 is applied subcutaneously once per week for 12 weeks in Arm 2. Due to priming doses up to 14 applications are planned. |
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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PSA response defined as ≥50% reduction in PSA at FU1 compared to baseline.
大体时间：Screening: 21 days before Cycle (C1);C1: Day (D) -1, D0 to D3, D8, D15, and D22; C2-3: D1, D8, D15, and D22 (each cycle is 22 days); End of Treatment (EOT): D29 of C3; Follow-Up 1-5: every 30 days after the EOT; End of study (EOS): 12 months after EOT
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PSA serum levels [ng/ml] are determined during screening, before every treatment, and then every 30 days until end of follow up. PSA serum levels for one study patient should be locally assessed in the same lab during the whole study treatment. Furthermore, 5ml serum are taken and should be processed locally and stored at -80 °C at the study site. Tübingen for central assessment of PSA. |
Screening: 21 days before Cycle (C1);C1: Day (D) -1, D0 to D3, D8, D15, and D22; C2-3: D1, D8, D15, and D22 (each cycle is 22 days); End of Treatment (EOT): D29 of C3; Follow-Up 1-5: every 30 days after the EOT; End of study (EOS): 12 months after EOT
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合作者和调查者
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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