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.

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.

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.