A First-in-human, Two-part Clinical Study to Assess the Safety, Tolerability and Activity of IV Doses of ICT01 as Monotherapy and in Combination With a Checkpoint Inhibitor, in Patients With Advanced-stage, Relapsed/Refractory Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 293
- 试验地点
- 54
- 主要终点
- Adverse Events (Parts 1 & 2)
研究概览
简要总结
Part 1 will be a dose escalation study of IV ICT01 (a monoclonal antibody targeting BTN3A) as monotherapy in patients with advanced solid or hematologic tumors, followed by a cohort examining the combination of ICT01 plus pembrolizumab (Keytruda). Part 2 will be a cohort expansion into 2 solid tumor indications and one hematologic malignancy for ICT01 monotherapy, and 3 solid tumor indications for the combination of ICT01 plus pembrolizumab.
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
- •Voluntarily signed informed consent form.
- •Relapsed/refractory patients with histologically or cytologically confirmed diagnosis of advanced-stage or recurrent cancer, including:
- •Group A: bladder, breast, colon, gastric, melanoma, ovarian, prostate and PDAC Group B: hematologic malignancies including acute myeloid leukemia, acute lymphocytic leukemia, Diffuse large B cell lymphoma and follicular lymphoma Group C: melanoma, cervical, bladder, gastric, head and neck SCC, and lymphoma (according to the approved package labeling of the ICI) Part 2, Group D: Ovarian cancer (2L/3L) with baseline g9d2 T cells > 20K Part 2, Group E: metastatic castrate resistant prostate cancer (2L/3L) with baseline g9d2 T cells > 20K Part 2, Group F: newly diagnosed AML starting venetoclax/azacitidine Part 2, Group G: checkpoint-refractory metastatic melanoma with g9d2 T cells >5K Part 2, Group H: chemotx-refractory or Pt-ineligible urotherlial cancer (bladder) with g9d2 T cells >5K Part 2, Group I: checkpoint-refractory, metastatic HNSCC with g9d2 T cells >5K
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- •Life expectancy > 3 months as assessed by the Investigator
- •At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST)/ Response Evaluation Criteria in Lymphoma (RECIL) or >5% marrow blasts
排除标准
- •Any malignancy of Vγ9Vδ2 T cell origin
- •Any anti-tumor-directed drug therapy within 28 days or 5 times the elimination half-life (whichever is shorter) before study treatment (does not apply to patients receiving ICI for the combination arm)
- •Treatment with investigational drug(s) 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 need for ongoing treatment.
- •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) and/or AEs ≥grade 2 not resolved from previous therapies except vitiligo, stable neuropathy up to grade 2, hair loss, and stable endocrinopathies with replacement hormone therapy.
- •Within 4 weeks of major surgery
- •Documented history of active autoimmune disorders requiring systemic immunosuppressive therapy within the last 12 months
- •Primary or secondary immune deficiency
- •Active and uncontrolled infections requiring intravenous antibiotic or antiviral treatment
研究组 & 干预措施
IV ICT01 Monotherapy
Up to six ICT01 dose levels administered as IV monotherapy every 3 weeks will be tested in Part 1 Dose Escalation and up to 2 dose levels in Part 2 Cohort Expansion
干预措施: IV ICT01 (Biological)
IV ICT01 + IV Pembrolizumab
A range of IV ICT01 doses administered every 3 weeks will be tested in combination with 200 mg pembrolizumab in Part 1 Dose Escalation and up to 2 dose levels of ICT01 plus 200 mg pembrolizumab in Part 2 Cohort Expansion
干预措施: IV ICT01 (Biological)
结局指标
主要结局
Adverse Events (Parts 1 & 2)
时间窗: 12 months
Incidence of treatment-emergent adverse events
Disease Control Rate using RECIST for solid tumor patients (Part 2)
时间窗: 12 months
RECIST is measured every 8 weeks during treatment
Disease Control Rate using RECIL for lymphoma patients (Part 2)
时间窗: 12 months
RECIL is measured every 8 weeks during treatment
Percentage of participants with TEAES (Part 1)
时间窗: From baseline to at least 6 months
Treatment emergent adverse events (TEAEs) with severity according to National Cancer Institute \[NCI\]- Common Terminology Criteria for Adverse Events \[CTCAE\] Version 5.0.
Percentage of participants with TEAES leading to discontinuation of study treatment or treatment modifications (Part 1)
时间窗: From baseline to at least 6 months
Treatment emergent adverse events (TEAEs) with severity according to National Cancer Institute \[NCI\]- Common Terminology Criteria for Adverse Events \[CTCAE\] Version 5.0.
Percentage of participants with SAEs (Part 1)
时间窗: From baseline to at least 6 months
Serious Adverse Events (SAEs) with severity according to National Cancer Institute \[NCI\]- Common Terminology Criteria for Adverse Events \[CTCAE\] Version 5.0
Percentage of participants with clinically significant change from baseline clinical laboratory abnormalities (Part 1)
时间窗: From baseline to at least 6 months
With severity measured according to NCI-CTCAE Version 5.0
Percentage of participants with clinically significant change from baseline vital sign readings (Part 1)
时间窗: From baseline to at least 6 months
Vital signs will be assessed by the investigators for clinical significance.
Percentage of participants with clinically significant change from baseline in 12-lead Electrocardiogram (ECG) readings (Part 1)
时间窗: From baseline to at least 6 months
12-lead (echocardiogram) ECGs will be assessed by the investigators for clinical significance.
Percentage of participants with clinically significant change from baseline physical examinations (Part 1)
时间窗: From baseline to at least 6 months
Physical examinations will be assessed by the investigators for clinical significance.
Duration of Complete Response (DCR) (Part 2)
时间窗: From baseline to at least 6 months
DCR according to RECIST Version 1.1 for all groups except Group F (complete response \[CR\] + partial response \[PR\] + stable disease \[SD\]);
次要结局
- Change from Baseline in the Activation State of Circulating Gamma Delta T Cells(28 days)
- AUC following the first dose of ICT01(21 days)
- Cmax following the first dose of ICT01(1 day)
- Change from Baseline in the Number of Circulating Gamma Delta T Cells(28 days)
- Half-life of ICT01(6 months)
- Clearance at steady-state of ICT01(6 months)
- Objective Response Rate using RECIST for solid tumor patients (Part 2)(12 months)