A Two-part, Open-label, Clinical Study to Assess the Safety, Tolerability and Activity of Intravenous Doses of ICT01 in Combination With Low-dose Subcutaneous Interleukin-2 in Patients With Advanced Solid Tumors (EVICTION-2)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 56
- 试验地点
- 9
- 主要终点
- Treatment-Emergent Adverse Events
研究概览
简要总结
This is a phase I/IIa, two-part, open-label study to characterize the safety, tolerability, pharmacodynamics, and antitumor activity of ICT01 in combination with LDSC IL-2 in patients with advanced-stage solid tumors.
Part 1 will be a dose escalation of IV ICT01 administered on the first day of every 21-day cycle (CnD1) to patients with advanced-stage solid tumors in combination with LDSC IL-2 (Proleukin®) administered daily on days 1-5 of cycles 1-3 (C1-3D1-5). Objectives of part 1 are to characterize the safety of the combination regimen and determine the RP2D for Part 2.
Part 2 will comprise a maximum of 2 indications and 2 combination dosing regimens of ICT01 +LDSC IL-2, which will be supported by statistical power calculations once the indications are selected. The final regimen will be ICT01 + LDSC IL-2 + Pembrolizumab on a Q3W cycle. The primary objective of Part 2 is to demonstrate the efficacy of the combination regimen based on RECIST1.1 in one or more solid tumor indications.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Relapsed/refractory patients who have failed at least 2 lines of systemic therapy or who failed first line therapy and are intolerant of or have a contraindication to the standard second line of therapy with histologically or cytologically confirmed diagnosis of:
- •metastatic colorectal cancer (CRC):
- •metastatic ovarian cancer:
- •metastatic castration-resistant prostate cancer (mCRPC)
- •metastatic pancreatic ductal adenocarcinoma (PDAC)
- •metastatic or unresectable refractory melanoma
- •2) Availability of baseline tumor biopsy and willingness to undergo on-study tumor biopsies 3) Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 4) Life expectancy > 3 months as assessed by the Investigator 5) At least 1 measurable lesion per RECIST1.1
排除标准
- •Any malignancy of γ9δ2 T cell origin
- •Any systemic anti-tumor-directed drug therapy within 28 days or 5 times the elimination half-life (whichever is shorter) before study treatment
- •Treatment with investigational drugs within 28 days before study treatment
- •Systemic steroids at a daily dose of > 10 mg of prednisone, > 2 mg of dexamethasone or equivalent, for the last 28 days and ongoing
- •Patients with rapidly progressing disease defined as advanced/metastatic, symptomatic, visceral spread, with a risk of life-threatening complications in the short term (e.g., during Screening Period/ treatment washout) that includes patients with massive uncontrolled effusions pleural, pericardial, peritoneal, pulmonary lymphangitis, and over 50% liver involvement
- •Ongoing immune-related adverse events (irAEs) ≥grade 2 not resolved from previous therapies except vitiligo, stable neuropathy up to grade 2, hair loss, and stable endocrinopathies with substitutive hormone therapy.
- •Ongoing systemic autoimmune disease requiring systemic immunosuppressive therapy
- •Primary or secondary immune deficiency
- •Active and uncontrolled infections requiring intravenous antibiotic or antiviral treatment
- •Patients with contraindication to IL-2 treatment according to the SmPC/package insert
研究组 & 干预措施
Dose level 3 ICT01 + Low dose SC IL-2
For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.
干预措施: ICT01 (Drug)
Primer Dose level 2 ICT01+ Low dose SC IL-2 + Booster Dose level 3 ICT01
ICT01 IV is given on Day 1 of every 21-day cycle and on day 8 of Cycles 1-3. SC IL-2 is administered on Days 1-5 of Cycles 1/2/3 only.
干预措施: ICT01 (Drug)
Dose level 2 ICT01 + Low dose SC IL-2 + Pembrolizumab
ICT01 IV and Pembrolizumab are given on Day 1 of every 21-day cycle. SC IL-2 is administred Days 1-5 of cycles 1/2/3 only.
干预措施: Pembrolizumab injection (Drug)
Dose level 2 ICT01 + Low dose SC IL-2
For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.
干预措施: ICT01 (Drug)
Dose level 2 ICT01 + Low dose SC IL-2
For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.
干预措施: Proleukin Injectable Product (Drug)
Dose Level 1 ICT01 + High dose SC IL-2
For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.
干预措施: ICT01 (Drug)
Dose Level 1 ICT01 + High dose SC IL-2
For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.
干预措施: Proleukin Injectable Product (Drug)
Dose level 1 ICT01 + Low dose SC IL-2
For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.
干预措施: ICT01 (Drug)
Dose level 1 ICT01 + Low dose SC IL-2
For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.
干预措施: Proleukin Injectable Product (Drug)
Dose level 3 ICT01 + Low dose SC IL-2
For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.
干预措施: Proleukin Injectable Product (Drug)
Dose level 5 ICT01 + Low dose SC IL-2
For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.
干预措施: ICT01 (Drug)
Dose level 5 ICT01 + Low dose SC IL-2
For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.
干预措施: Proleukin Injectable Product (Drug)
Primer Dose level 2 ICT01+ Low dose SC IL-2 + Booster Dose level 2 ICT01
ICT01 IV is given on Day 1 of every 21-day cycle and on day 8 of Cycles 1-3. SC IL-2 is administered on Days 1-5 of Cycles 1/2/3 only.
干预措施: ICT01 (Drug)
Primer Dose level 2 ICT01+ Low dose SC IL-2 + Booster Dose level 2 ICT01
ICT01 IV is given on Day 1 of every 21-day cycle and on day 8 of Cycles 1-3. SC IL-2 is administered on Days 1-5 of Cycles 1/2/3 only.
干预措施: Proleukin Injectable Product (Drug)
Primer Dose level 2 ICT01+ Low dose SC IL-2 + Booster Dose level 3 ICT01
ICT01 IV is given on Day 1 of every 21-day cycle and on day 8 of Cycles 1-3. SC IL-2 is administered on Days 1-5 of Cycles 1/2/3 only.
干预措施: Proleukin Injectable Product (Drug)
Dose level 2 ICT01 + Low dose SC IL-2 + Pembrolizumab
ICT01 IV and Pembrolizumab are given on Day 1 of every 21-day cycle. SC IL-2 is administred Days 1-5 of cycles 1/2/3 only.
干预措施: ICT01 (Drug)
Dose level 2 ICT01 + Low dose SC IL-2 + Pembrolizumab
ICT01 IV and Pembrolizumab are given on Day 1 of every 21-day cycle. SC IL-2 is administred Days 1-5 of cycles 1/2/3 only.
干预措施: Proleukin Injectable Product (Drug)
Dose level 4 ICT01 + Low dose SC IL-2 + Pembrolizumab
ICT01 IV and Pembrolizumab are given on Day 1 of every 21-day cycle. SC IL-2 is administred Days 1-5 of cycles 1/2/3 only.
干预措施: ICT01 (Drug)
Dose level 4 ICT01 + Low dose SC IL-2 + Pembrolizumab
ICT01 IV and Pembrolizumab are given on Day 1 of every 21-day cycle. SC IL-2 is administred Days 1-5 of cycles 1/2/3 only.
干预措施: Proleukin Injectable Product (Drug)
Dose level 4 ICT01 + Low dose SC IL-2 + Pembrolizumab
ICT01 IV and Pembrolizumab are given on Day 1 of every 21-day cycle. SC IL-2 is administred Days 1-5 of cycles 1/2/3 only.
干预措施: Pembrolizumab injection (Drug)
Primer Dose level 2 ICT01+ Low dose SC IL-2 + Pembrolizumab + Booster Dose level 2 ICT01
ICT01 IV and Pembrolizumab are given on Day 1 of every 21-day cycle. ICT01 IV is given on day 8 of Cycles 1-3. SC IL-2 is administered on Days 1-5 of Cycles 1/2/3 only.
干预措施: ICT01 (Drug)
Dose level 4 ICT01 + Low dose SC IL-2
For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.
干预措施: ICT01 (Drug)
Dose level 4 ICT01 + Low dose SC IL-2
For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.
干预措施: Proleukin Injectable Product (Drug)
Primer Dose level 2 ICT01+ Low dose SC IL-2 + Pembrolizumab + Booster Dose level 2 ICT01
ICT01 IV and Pembrolizumab are given on Day 1 of every 21-day cycle. ICT01 IV is given on day 8 of Cycles 1-3. SC IL-2 is administered on Days 1-5 of Cycles 1/2/3 only.
干预措施: Proleukin Injectable Product (Drug)
Primer Dose level 2 ICT01+ Low dose SC IL-2 + Pembrolizumab + Booster Dose level 2 ICT01
ICT01 IV and Pembrolizumab are given on Day 1 of every 21-day cycle. ICT01 IV is given on day 8 of Cycles 1-3. SC IL-2 is administered on Days 1-5 of Cycles 1/2/3 only.
干预措施: Pembrolizumab injection (Drug)
结局指标
主要结局
Treatment-Emergent Adverse Events
时间窗: 1 year
Incidence and severity of adverse events related to study treatment
次要结局
- Change from baseline in the number of circulating g9d2 T cells(Cycle Days 8 & 15 for the first 3 cycles)
- Disease Control Rate(1 year)