SENTI-202-101: A Phase 1, Multicenter, Open-Label Study of SENTI-202, a Selective Off-the-Shelf Logic Gated CAR NK Cell Therapy, in Subjects With CD33 and/or FLT3 Expressing Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 21
- 试验地点
- 8
- 主要终点
- Safety and tolerability for dose determination of SENTI-202
研究概览
简要总结
This is an open-label study of the safety, biodynamics, and anti-cancer activity of SENTI-202 (an off-the-shelf logic gated CAR NK cell therapy) in patients with CD33 and/or FLT3 expressing blood cancers, including AML and MDS.
详细描述
This is a dose-finding study of SENTI-202, comprised of an initial dose finding using a modified "3+3" study design to determine the maximum tolerated dose (MTD) and/or recommended phase two dose (RP2D) of SENTI-202 when administered after lymphodepleting chemotherapy (Part 1) followed by disease-specific expansion cohorts at the RP2D (Part 2).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with CD33 and/or FLT3 expressing malignancies, including:
- •Relapsed refractory acute myeloid leukemia (AML) with morphologic relapse as defined by ≥5% bone marrow blasts who have received at least 1 prior line, but no more than 3 prior lines of standard anti-AML therapy. Subjects with FLT3-mutated or IDH ½-mutated disease must have received at least one prior targeted therapy.
- •Relapsed refractory myelodysplastic syndrome (MDS) with increased blasts who have received at least 1 prior line, but no more than 2 prior lines of anti-MDS therapy
- •Other hematological malignancies who have received at least 1 prior line of standard of care for the respective disease
- •Documentation of CD33 expression (or FLT3 expression if available) by individual institutional standard of care
- •ECOG performance score of 0-1
- •Adequate organ function including platelet count >20x109/L (platelet transfusion is permitted)
- •Adequate recovery from toxicities from previous cancer treatments, as described in the study protocol
- •Willing and able to provide written informed consent
排除标准
- •White blood cell (WBC) count of ≥20×109/L or circulating blasts ≥10×109/L or rapidly progressive/hyperproliferative disease
- •Acute promyelocytic leukemia with t(15;17) (q22;q12) or abnormal promyelocytic leukemia/retinoic acid receptor alpha (APML-RARA)
- •MDS with fibrosis (MDS-f) or known prior history of constitutional conditions/syndromes with chemo-responsive AML
- •Evidence of leukemic meningitis or known active central nervous system disease
- •Presence of extra-medullary disease or myeloid sarcoma alone with no morphologic hematologic relapse
- •Prior use of certain anti-cancer therapies and/or use within a certain number of days prior to SENTI-202 study treatment, as described in the study protocol
- •Hematopoietic cell transplantation (HCT) less than 100 days prior to the first dose of SENTI-202
- •Prior NK cell or CAR T cell therapy at any time
- •Prior donor lymphocyte infusion (DLI), except if after HCT for MRD+ disease
- •Medical conditions or medications prohibited by the study protocol
- •Pregnant or breastfeeding female
研究组 & 干预措施
SENTI-202 CAR NK cell therapy
Part 1 Dose Finding: Sequential cohorts will receive doses of SENTI-202 using a modified 3+3 study design to determine the recommended phase 2 dose (RP2D). The starting dose will be 1 billion cells. Other doses may be explored depending on study data.
Part 2 Cohort Expansion: After determination of the RP2D, additional subjects will be enrolled in disease-specific expansion cohorts at that dose to further explore safety, biodynamics, and anti-cancer activity of SENTI-202
干预措施: SENTI-202 (Biological)
结局指标
主要结局
Safety and tolerability for dose determination of SENTI-202
时间窗: At the end of each treatment cycle (each cycle is 28 days) and through study completion, up to 2 years
Incidence, type, frequency, and severity of adverse events and dose limiting toxicities will be assessed to determine the maximum tolerated dose and/or recommended phase 2 dose and dosing regimen
For subjects enrolled in the Dose Expansion Cohort(s): Anti-cancer activity of SENTI-202
时间窗: Through study completion, up to 2 years
The response rate to SENTI-202 will be measured using clinical measures of benefit as defined by standard consensus criteria for the respective disease
次要结局
- Pharmacokinetic (PK) and pharmacodynamic (PDn) profile of SENTI-202(Through study completion, up to 2 years)
- Host immune response to SENTI-202(Through study completion, up to 2 years)
- For subjects enrolled in the Dose Finding Cohorts: Anti-cancer activity of SENTI-202(Through study completion, up to 2 years)