A Phase Ib Single-arm Clinical Study of HS-IT101 Injection for Advanced NSCLC
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Adverse Events (AE)
研究概览
简要总结
An Open-Label, Single-Arm Phase Ib Clinical Trial Evaluating the Safety, Tolerability, and Preliminary Efficacy of HS-IT101 Injection in Subjects with Advanced NSCLC.
详细描述
A Single-Arm, Open-Label, Interventional Study Evaluating Adoptive Cell Therapy (ACT) with Autologous Tumor-Infiltrating Lymphocytes (HS-IT101) Following Lymphodepleting Conditioning with Fludarabine and Cyclophosphamide, Followed by IL-2 in Patients with Advanced NSCLC.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: 18-70 years (inclusive).
- •Histologically/cytologically confirmed advanced, recurrent, or metastatic non-small cell lung cancer (NSCLC) .
- •Tumor Sampling:
- •≥1 lesion untreated with radiotherapy/local therapy within 28 days for TIL preparation (tissue weight ≥0.050 g).
- •Target Lesion:
- •≥1 measurable lesion per RECIST v1.1, untreated with radiotherapy/local therapy (unless treatment occurred >28 days before sampling with documented progression).
- •Performance Status: ECOG score ≤
- •Survival: Life expectancy ≥3 months.
- •Organ Function:
- •Hematology: ANC ≥1.5×10⁹/L, PLT ≥90×10⁹/L, HGB ≥90 g/L (no transfusion/erythropoietin within 14 days).
- •Liver: ALT/AST ≤2.5×ULN (≤5×ULN if liver metastases); TBil ≤1.5×ULN (≤3×ULN for Gilbert syndrome).
- •Kidney: Serum Cr ≤1.5×ULN or Ccr ≥60 mL/min (Cockcroft-Gault formula). Coagulation: APTT ≤1.5×ULN; INR/PT ≤1.5×ULN.
- •Cardiac Function:
- •LVEF ≥50% by echocardiography; QTcF ≤470 ms (Fridericia formula: QTcF = QT/RR⁰·³³).
- •Baseline SpO₂ >91% (room air). Note: If QTcF is abnormal initially, repeat twice at ≥5-minute intervals and use mean value for eligibility.
- •Toxicity Recovery: All treatment-related adverse events resolved to CTCAE v5.0 ≤Grade 1 (except alopecia/non-risk toxicities per investigator) before tumor sampling.
- •Contraception: Effective non-pharmacological contraception from informed consent until 1 year post-TIL infusion.
- •Compliance: Capable of understanding the trial, voluntarily signing informed consent, and adhering to protocol visits/procedures.
排除标准
- •Severe Hypersensitivity: History of severe hypersensitivity to drugs used in the study (including but not limited to cyclophosphamide, fludarabine, IL-2, gentamicin, amphotericin B, or components of TIL infusion).
- •Uncontrolled Comorbidities:
- •Poorly controlled hypertension (resting SBP ≥160 mmHg or DBP ≥100 mmHg despite medication).
- •Congestive heart failure (NYHA Class III/IV).
- •Cardiovascular Events (within 6 months):
- •Deep vein thrombosis, pulmonary embolism, myocardial infarction, severe/unstable arrhythmia, angina, PCI, ACS, CABG, stroke, TIA, or cerebral embolism.
- •Active Autoimmune Disease:
- •Requires systemic therapy during the study period (Exceptions: Eczema, vitiligo, psoriasis, alopecia, or Graves' disease stable without systemic therapy for 2 years; hypothyroidism on hormone replacement; type 1 diabetes on insulin).
- •Transplantation History: Solid organ or hematopoietic stem cell transplantation.
- •Immunosuppressive Therapy:
- •Use of immunosuppressants (e.g., steroids) within 4 weeks before tumor sampling (Allowed: Physiologic glucocorticoid doses ≤12 mg/m²/day hydrocortisone equivalent; topical/nasal steroids).
- •Recent Anticancer Therapy:
- •Systemic anticancer treatment within 4 weeks before preconditioning (including investigational drugs; washout <5 half-lives if <4 weeks).
- •Planned participation in other interventional trials.
- •Active Infections:
- •HIV/syphilis antibody-positive; active HBV/HCV (Allowed: HBsAg/HBeAg+ if HBV DNA below LLN; HCV Ab+ if HCV RNA below LLN).
- •Active systemic infection or tuberculosis requiring treatment. Recent Surgery/Trauma: Major surgery or significant trauma within 4 weeks before screening; elective surgery planned during the study.
- •Poor Wound Healing: Surgery-related complications or delayed healing increasing risks of TIL therapy (per investigator judgment).
- •Other Malignancies: Additional primary malignancy within 5 years (Exceptions: Curatively treated basal/squamous cell carcinoma or carcinoma in situ).
- •Severe Respiratory Disease: History of severe ILD, COPD, pulmonary insufficiency, or symptomatic bronchospasm.
- •Gastrointestinal Complications: Surgical-required GI bleeding, bowel ischemia, or perforation.
- •CNS Involvement:
- •Leptomeningeal metastasis; uncontrolled/untreated CNS metastases (Exceptions: Asymptomatic lesions <1 cm, stable for ≥4 weeks without steroids/anticonvulsants).
- •Prior Cell Therapy: Previous treatment with similar cellular products. Pregnancy/Lactation: Pregnant or breastfeeding women.
- •Other Exclusions:
- •Psychiatric disorders, alcoholism, drug abuse, or other conditions deemed unsuitable by the investigator.
研究组 & 干预措施
HS-IT101 monotherapy
TIL Injection administered by intravenous infusion over 30-60 minutes.
干预措施: HS-IT101 monotherapy (Drug)
HS-IT101 monotherapy
TIL Injection administered by intravenous infusion over 30-60 minutes.
干预措施: IL-2 (interleukin 2) (Drug)
HS-IT101 monotherapy
TIL Injection administered by intravenous infusion over 30-60 minutes.
干预措施: Cyclophosphamide (Drug)
HS-IT101 monotherapy
TIL Injection administered by intravenous infusion over 30-60 minutes.
干预措施: Fludarabine (Drug)
结局指标
主要结局
Adverse Events (AE)
时间窗: 12 months
To characterize the safety profile of HS-IT101 in patients with advanced solid tumor as assessed by incidence of adverse events
Serious Adverse Events (SAE)
时间窗: 12 months
To characterize the safety profile of HS-IT101 in patients with advanced solid tumor as assessed by incidence of serious adverse events
Objective Response Rate (ORR)
时间窗: Up to 36 months
To evaluate the efficacy of HS-IT101 in patients with advanced solid tumor, based on the objective response rate (ORR) as assessed by the Independent Review Committee (IRC) per RECIST v1.1
Time-to-response (TTR)
时间窗: Up to 36 months
To evaluate the efficacy of HS-IT101 in patients with advanced solid tumor by assessing the time-to-response (TTR) as assessed by the Investigator per RECIST v1.1
Duration of Response (DOR)
时间窗: Up to 36 months
To evaluate the efficacy of HS-IT101 in patients with advanced solid tumor by assessing the duration of response (DOR) as assessed by the Investigator per RECIST v1.1
Disease Control Rate (DCR)
时间窗: Up to 36 months
To evaluate the efficacy of HS-IT101 in patients with advanced solid tumor, based on the disease control rate (DCR) as assessed by the Independent Review Committee (IRC) per RECIST v1.1
次要结局
- Progression-Free-Survival (PFS)(Up to 36 months)
- Overall Survival (OS)(Up to 36 months)
- Pharmacokinetic (PK) detection parameters for HS-IT101(Up to 6 months)