An Open-Label, Dose-Escalation Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Profile, and Preliminary Efficacy of NK Cell Injection in the Treatment of Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 9
- 主要终点
- Dose-limiting toxicity (DLT)
研究概览
简要总结
This is an open-label, single-arm, dose-escalation Phase I clinical study designed to evaluate the safety, tolerability, pharmacokinetic profile, and preliminary efficacy of NK Cell Injection in patients with advanced solid tumors.
Eligible participants who have signed written informed consent will be screened and, if qualified, assigned a enrollment number and sequentially assigned to the designated dose group.
The study employs a traditional "3+3" dose-escalation design. Each dose group enrolls at least 3 participants, with each participant receiving only one corresponding dose level, until the MTD or RP2D is determined.
The study consists of four periods: Screening Period, Treatment Period (including lymphodepleting chemotherapy), Safety Follow-up Period, and Survival Follow-up Period.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 75 years (inclusive), regardless of sex;
- •Histologically or cytologically confirmed advanced solid tumor;
- •Failed standard treatment, or no standard treatment available, or standard treatment not currently applicable;
- •At least one measurable lesion per RECIST 1.1 (non-lymph node lesion >= 1.0 cm in long diameter, or lymph node lesion >= 1.5 cm in short diameter); lesions previously treated with local therapy (e.g., radiotherapy or interventional therapy) cannot be considered target lesions unless there is imaging evidence of definitive progression;
- •Adequate bone marrow and organ function:
- •ANC >= 1.5 x 10^9/L;
- •Platelet count > 100 x 10^9/L;
- •Hemoglobin >= 9 g/dL;
- •Total bilirubin < 1.5 x ULN; ALT and AST < 3 x ULN (for liver metastases or primary hepatocellular carcinoma: total bilirubin < 2.5 x ULN, ALT and AST < 5 x ULN);
- •Serum creatinine <= 1.5 x ULN;
- •PT, APTT, INR < 1.5 x ULN;
- •ECOG performance status 0-1;
- •Expected survival >= 3 months;
- •Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to cell infusion, and must agree to use reliable contraception during the study and for 6 months after cell infusion; male participants with partners of childbearing potential must agree to use reliable contraception during the study and for 6 months after cell infusion;
- •Willing to participate voluntarily and sign the informed consent form (ICF), and able to comply with follow-up requirements.
排除标准
- •Other malignancies within 5 years prior to screening (except completely resolved carcinoma in situ and malignancies judged by the investigator to be slow-progressing);
- •History of leptomeningeal metastasis or CNS metastasis, or definite CNS underlying disease with significant residual symptoms within 6 months prior to cell infusion (asymptomatic brain metastasis or stable symptoms after treatment without corticosteroid use may be allowed);
- •Clinically symptomatic moderate to severe third-space effusion requiring therapeutic drainage (except for minimal effusion on imaging without clinical symptoms);
- •Severe cardiovascular disease history, including but not limited to: severe arrhythmia or conduction abnormalities requiring clinical intervention; QTcF > 450 ms (male) or > 470 ms (female); acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other >= Grade 3 cardiovascular events within 6 months prior to screening; NYHA functional classification >= II or LVEF < 50%; uncontrolled hypertension (SBP >= 160 mmHg and/or DBP >= 100 mmHg);
- •Any active infection (viral, bacterial, fungal) currently under treatment, or any infection requiring >= 7 days of IV antibiotics within the past 6 weeks, or any active infection requiring oral antibiotics within the past 1 week;
- •Active autoimmune disease or history of severe autoimmune disease requiring long-term immunosuppressive therapy;
- •Allergy to lymphodepleting chemotherapy (cyclophosphamide, fludarabine) and/or any component of the study product;
- •Prior treatment with other cell therapy products (e.g., DC, CIK, T cells, NK cells, CAR-T, etc.) other than the study product;
- •Received other anti-tumor treatment (chemotherapy, targeted therapy, immunotherapy, interventional therapy, or Chinese patent medicine with anti-tumor indications) within 4 weeks prior to infusion;
- •Participated in other clinical trials within 3 months prior to infusion;
- •Toxicity or complications from prior intervention or treatment not resolved to Grade 2 or below (except alopecia and <= Grade 2 peripheral sensory neuropathy);
- •Untreated chronic active hepatitis B, or chronic HBV carrier with HBV DNA >= 1000 copies/mL; HCV antibody positive and HCV-RNA positive; HIV antibody positive; Treponema pallidum antibody positive;
- •Other severe organic diseases or psychiatric disorders;
- •Pregnant or lactating women;
- •Any other condition that, in the investigator's judgment, makes the participant unsuitable for this clinical study.
研究组 & 干预措施
Dose-escalation Phase I clinical study
Group 1: 2 x 10^9 cells/dose Group 2: 4 x 10^9 cells/dose Group 3: 8 x 10^9 cells/dose
Optional higher dose group: 1 x 10^10 cells/dose (if safety is well-tolerated within the 2-8 x 10^9 cells/dose range, upon SRC assessment after completion of the 8 x 10^9 cells/dose DLT observation period).
Each dose group must include at least 1 female participant.
干预措施: NK CELLS (Biological)
结局指标
主要结局
Dose-limiting toxicity (DLT)
时间窗: Up to 21 days post first infusion
Incidence of DLT assessed during the single-infusion DLT observation period (14 days post single infusion) and the multiple-infusion DLT observation period (first cycle, 21 days). DLT is defined per the protocol-specified DLT criteria.
Maximum tolerated dose (MTD) and recommended Phase II dose (RP2D)
时间窗: Estimated up to 24 months from first enrollment
MTD defined as the highest dose level at which ≤33% of DLT-evaluable participants experience DLT, per protocol-specified dose-escalation rules. RP2D determined based on safety, PK, and preliminary activity across completed dose levels.
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
时间窗: From first infusion through end of safety follow-up (approximately 30 days after last infusion)
All-cause AEs and SAEs, including clinically significant laboratory abnormalities, graded per NCI-CTCAE v6.0. Severity classified by CTCAE grade; relationship to study treatment assessed by investigator.
次要结局
- Objective Response Rate(Every 6 weeks thereafter up to 24 months.)
- Progression-Free Survival (PFS)(From date of first dose until the date of first documented progression or death from any cause, whichever occurs first, assessed up to approximately 24 months)
- Duration of Response(From date of first documented response until the date of first documented progression or death, assessed up to approximately 24 months.)
- Disease Control Rate(every 6 weeks thereafter up to 24 months)
- Overall Survival (OS)(From date of first dose until the date of death from any cause, assessed up to approximately 2 years.)
- Quality of Life- EORTC QLQ-C30 Global Health Status and Functional Scales(every 6 weeks thereafter,up to approximately 24 months.)
- Change in Lymphocyte Subsets and Soluble Immune Mediators(At baseline (C0D1; pre-dose) through end of treatment,up to approximately 24 months.)
- Quality of Life - EQ-5D-5L Utility Index and Visual Analog Scale(every 6 weeks thereafter, up to approximately 24 months)