NK Cell Injection for Advanced Solid Tumors

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

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.

Inclusion Criteria:

1. Age 18 to 75 years (inclusive), regardless of sex;

2. Histologically or cytologically confirmed advanced solid tumor;

3. Failed standard treatment, or no standard treatment available, or standard treatment not currently applicable;

4. 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;

5. 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;

6. ECOG performance status 0-1;

7. Expected survival >= 3 months;

8. 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;

9. Willing to participate voluntarily and sign the informed consent form (ICF), and able to comply with follow-up requirements.

Exclusion Criteria:

1. Other malignancies within 5 years prior to screening (except completely resolved carcinoma in situ and malignancies judged by the investigator to be slow-progressing);
2. 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);
3. Clinically symptomatic moderate to severe third-space effusion requiring therapeutic drainage (except for minimal effusion on imaging without clinical symptoms);
4. 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);
5. 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;
6. Active autoimmune disease or history of severe autoimmune disease requiring long-term immunosuppressive therapy;
7. Allergy to lymphodepleting chemotherapy (cyclophosphamide, fludarabine) and/or any component of the study product;
8. Prior treatment with other cell therapy products (e.g., DC, CIK, T cells, NK cells, CAR-T, etc.) other than the study product;
9. 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;
10. Participated in other clinical trials within 3 months prior to infusion;
11. Toxicity or complications from prior intervention or treatment not resolved to Grade 2 or below (except alopecia and <= Grade 2 peripheral sensory neuropathy);
12. 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;
13. Other severe organic diseases or psychiatric disorders;
14. Pregnant or lactating women;
15. Any other condition that, in the investigator's judgment, makes the participant unsuitable for this clinical study.