Advanced Non-Small Cell Lung Cancer
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGCyclophosphamide
Cyclophosphamide administered via intravenous infusion once daily for 3 consecutive days.
DRUGFludarabine
Fludarabine is administered once daily via intravenous infusion for 4 consecutive days.
IL-2 administered subcutaneously once daily. Dosing may be adjusted based on subject tolerance, including modifications to dose quantity, administration frequency, or complete treatment discontinuation, with a maximum treatment duration of 3 days.
TIL Injection administered by intravenous infusion over 30-60 minutes.
Sponsors
Qingdao Sino-Cell Biomedicine Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age: 18-70 years (inclusive). Diagnosis: 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 ≤1. 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | 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 |
| Objective Response Rate (ORR) | 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) | 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) | 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 |
| Adverse Events (AE) | 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) | 12 months | To characterize the safety profile of HS-IT101 in patients with advanced solid tumor as assessed by incidence of serious adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to 36 months | To evaluate overall survival (OS) in patients with advanced solid tumor |
| Pharmacokinetic (PK) detection parameters for HS-IT101 | Up to 6 months | peripheral blood lymphocyte subsets . |
| Progression-Free-Survival (PFS) | Up to 36 months | To evaluate progression-free-survival (PFS) in patients with advanced solid tumor |
Countries
China
Contacts
Primary ContactWenNa.Liu
Outcome results
None listed