Immuno-pet IMaging ResPonses AdministeRed Immune CheckpoiNt InhibiTor (IMPRINT)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Number of participants with successful completion of curative surgery within 42 days after start of subcutaneous sasanlimab as neo-adjuvant treatment.
研究概览
简要总结
This study investigates whether a single subcutaneous administration of anti-PD-1 antibody can induce CD8+ T-cell tumor-infiltration that can be non-invasively monitored with [89Zr]crefmirlimab berdoxam PET imaging as an imaging biomarker.
详细描述
This is a two-armed open-label feasibility study with exploratory endpoints, where subjects are participating for 2 years after completement of enrollment to determine disease-free survival rates. The therapeutic intervention is a single subcutaneous administration of the humanized hinge region-stabilized IgG4 monoclonal anti-PD1 antibody PF-06801591 (sasanlimab) in a fixed dose of 300 mg in a neo-adjuvant setting, with or without radiation therapy, followed by curative-intended surgery. The diagnostic intervention is a radiolabeled imaging tracer [89Zr]Zr-crefmirlimab berdoxam that entails two intravenous administrations of a fixed dose of 1.5 mg protein dose labelled with activity dose 37 MBq Zirconium-89; one at baseline and one at 2 weeks after sasanlimab injection, to visualize CD8+ T-cells in vivo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >50 years
- •Histologically or cytologically proven adenocarcinoma or squamous cell lung cancer
- •Primary tumors >1 cm and </= 5 cm largest diameter
- •Scheduled for curative surgery
- •Informed consent
- •Adequate bone marrow function (ANC >/= 1500, platelets >/=100k, Hgb > 9), renal function (CLCr >30 mL/min), liver function (TotalBili </= 1.5 x ULN; AST and ALT </=2.5 x ULN).
排除标准
- •Inability to undergo SPECT or PET scans
- •Pleiomorphic, lepidic, mucinous or large cell neuro-endocrine histological subtypes of non-small cell lung carcinoma
- •Histologically confirmed druggable mutation (EGFR, RET, ROS, ALK, BRAF V600, NTRK, NRG1, MET ex14Sk)
- •Pregnancy or lactation
- •Active infection, auto-immune disease, prior organ-transplantation or haematological condition that requires medication that potentially interferes with immune cell activation.
- •Documented medical history of auto-immune disease, organ-transplantation or haematological condition that potentially interferes with immune cell behavior
- •Prior radiation therapy to the chest
- •Splenectomy
- •Enrolled in a current investigational drug trial
研究组 & 干预措施
Site EKUT (Tuebingen)
Patients will receive a single subcutaneous administration of the immunotherapy sasanlimab in a fixed dose of 300 mg in a neo-adjuvant setting, followed by curative-intended surgery.
Patients will also receive a radiolabeled imaging tracer [89Zr]Zr-crefmirlimab berdoxam that entails two intravenous administrations of a fixed dose of 1.5 mg protein dose labelled with activity dose 37 MBq Zirconium-89; one at baseline and one at 2 weeks after sasanlimab injection.
干预措施: Sasanlimab (Drug)
Site EKUT (Tuebingen)
Patients will receive a single subcutaneous administration of the immunotherapy sasanlimab in a fixed dose of 300 mg in a neo-adjuvant setting, followed by curative-intended surgery.
Patients will also receive a radiolabeled imaging tracer [89Zr]Zr-crefmirlimab berdoxam that entails two intravenous administrations of a fixed dose of 1.5 mg protein dose labelled with activity dose 37 MBq Zirconium-89; one at baseline and one at 2 weeks after sasanlimab injection.
干预措施: [89Zr]Zr-crefmirlimab berdoxam (Drug)
Site Radboudumc (Nijmegen)
Patients will receive a single subcutaneous administration of the immunotherapy sasanlimab in a fixed dose of 300 mg in a neo-adjuvant setting, and 3 days of non-ablative dose radiation therapy starting with sasanlimab injection. This is followed by curative-intended surgery.
Patients will also receive a radiolabeled imaging tracer [89Zr]Zr-crefmirlimab berdoxam that entails two intravenous administrations of a fixed dose of 1.5 mg protein dose labelled with activity dose 37 MBq Zirconium-89; one at baseline and one at 2 weeks after sasanlimab injection.
干预措施: Sasanlimab (Drug)
Site Radboudumc (Nijmegen)
Patients will receive a single subcutaneous administration of the immunotherapy sasanlimab in a fixed dose of 300 mg in a neo-adjuvant setting, and 3 days of non-ablative dose radiation therapy starting with sasanlimab injection. This is followed by curative-intended surgery.
Patients will also receive a radiolabeled imaging tracer [89Zr]Zr-crefmirlimab berdoxam that entails two intravenous administrations of a fixed dose of 1.5 mg protein dose labelled with activity dose 37 MBq Zirconium-89; one at baseline and one at 2 weeks after sasanlimab injection.
干预措施: non-ablative radiotherapy (Radiation)
Site Radboudumc (Nijmegen)
Patients will receive a single subcutaneous administration of the immunotherapy sasanlimab in a fixed dose of 300 mg in a neo-adjuvant setting, and 3 days of non-ablative dose radiation therapy starting with sasanlimab injection. This is followed by curative-intended surgery.
Patients will also receive a radiolabeled imaging tracer [89Zr]Zr-crefmirlimab berdoxam that entails two intravenous administrations of a fixed dose of 1.5 mg protein dose labelled with activity dose 37 MBq Zirconium-89; one at baseline and one at 2 weeks after sasanlimab injection.
干预措施: [89Zr]Zr-crefmirlimab berdoxam (Drug)
结局指标
主要结局
Number of participants with successful completion of curative surgery within 42 days after start of subcutaneous sasanlimab as neo-adjuvant treatment.
时间窗: 2 years
Feasibility will be determined on all patients who have entered the treatment phase of the study, i.e. received at least one course of neo-adjuvant sasanlimab. Feasibility is defined as successful completion of curative surgery within 42 days after start of neo-adjuvant treatment (= day 1). No delays will be allowed. Results will be reported in a descriptive fashion, including percentages, mean and standard deviation, median and range for the time-related measures.
The number of CTC grade ≥3 toxicity related to subcutaneous sasanlimab as neo-adjuvant treatment.
时间窗: 2 years
Safety will be defined as the number of CTC grade ≥3 toxicity related to neo-adjuvant sasanlimab. Results will be reported in a descriptive fashion.
Detection of treatment induced immune related responses after subcutaneous sasanlimab as neo-adjuvant treatment.
时间窗: 2 years
Efficacy will be defined as the detection of treatment induced immune related responses in \>15% of the patients. Results will be reported in a descriptive fashion, for both cohorts of each n=10 patients (sasanlimab with and without radiotherapy).
次要结局
- Demonstrate induction of CD8+ T-cells(2 years)
- Framework for PETscan interpretation(2 years)
- Explore pathological response rate(2 years)
- Identify immune signatures(2 years)