SK-NK Injection in Patients With Advanced Solid Tumors Accompanied by Malignant Ascites

A Single-arm, Prospective, Open-label, Phase I/II Study of Allogeneic NK Cell Injection (SK-NK Injection) in the Treatment of Patients With Advanced or Metastatic Malignant Solid Tumors Accompanied by Malignant Ascites

This study is divided into two phases. Patients with recurrent or metastatic solid tumors accompanied by malignant ascites who have failed previous standard treatments are enrolled. The first phase is a single-arm, open-dose exploratory Phase I clinical study. In this phase, two dose groups are preset, namely 20×108 cells and 30×108 cells. Subjects who meet the inclusion criteria will receive intravenous infusion of SK-NK injection. Once a week for 6 consecutive infusions. After completing 6 consecutive infusions of SK-NK injection, the researchers evaluated that the patient benefited and could continue to receive 6 consecutive infusions of SK-NK injection. After completing 12 infusions, whether to continue the treatment subsequently could be determined based on the patient's condition. The second stage will be based on the results of the first stage to further verify the clinical efficacy, safety, tolerability and pharmacokinetic characteristics of RP2D, etc.

Inclusion Criteria：

1. Aged 18 to 75 years.
2. Malignant solid tumors confirmed by histology or pathology, including: advanced gastric cancer, colorectal cancer, esophageal squamous cell carcinoma, gynecological malignancies, etc. that have failed at least two lines of treatment.
3. Pathological diagnosis or clinical diagnosis combined with malignant ascites, and ascites drainage is not required within one week before the administration of the study.
4. At least one measurable tumor lesion based on RECIST V1.1 criteria.
5. ECOG PS ≤1.
6. Expected survival ≥12 weeks.
7. Adequate organ function.
8. Non-reproductive female patients, or reproductive female patients whose pregnancy test results are negative and commit to taking adequate and effective contraceptive measures or abstinence from the screening period until 3 months after the last administration, or male patients commit to taking adequate and effective contraceptive measures or abstinence from the screening period until 3 months after the last administration.
9. Understands and provides written informed consent and willing to follow the requirements specified in protocol.

Exclusion Criteria:

1. History of severe allergic reactions to protein drugs
2. Have received NK cell therapy in the past.
3. Untreated, unstable or uncontrolled central nervous system (CNS) metastases.
4. Tumor invasion of vital arteries resulting in high risk of bleeding, significant risk of perforation or already formed fistulae.
5. Major surgeries within 4 weeks before enrollment or are planned to undergo major surgeries during the trial (excluding exploration surgeries).
6. New infections or concurrent infections occurred within 14 days before enrollment and have not yet been controlled to clinical stability.
7. Prior to the first study dose, systemic chemotherapy and anti-tumor monoclonal antibody drug therapy has been completed for at least 4 weeks; small molecule targeted drug therapy has been completed for at least 2 weeks or 5 half-lives of the drug (whichever is longer); intraperitoneal chemotherapy has been completed for at least 2 weeks; and treatment with proprietary Chinese medicines approved by the National Medicines and Pharmaceutical Administration (NMPA) as antitumor and having antitumor effects has been completed for at at least 2 weeks.
8. Patients with severe respiratory disease at the time of screening that results in respiratory failure or who, in the judgment of the investigator, are not suitable for enrollment.
9. Active autoimmune disease.except that the following are allowed to enter the screen: type I diabetes mellitus, hypothyroidism that can be controlled by replacement therapy only, and skin conditions (e.g., vitiligo, psoriasis, or alopecia areata) not requiring systemic therapy.
10. Patients had severe cardiovascular disease at screening, with an acute cardiovascular event or pulmonary embolism within the last 6 months or vascular stenting within 6 months; or venous thrombotic disease, such as lower extremity venous thrombosis, within the last 1 month.
11. Intestinal obstruction or gastrointestinal bleeding within 30 days prior to enrollment.
12. Objective reasons for not being able to drain ascites adequately (including segregation of ascites) or in combination with coeliac ascites.
13. Confirmed portal vein embolism or portal hypertension on examination.
14. Active chronic hepatitis B, active hepatitis C, positive human immunodeficiency virus (HIV) antibodies or active syphilis infection.
15. Combined with pleural effusion and causing clinical symptoms such as chest tightness and dyspnea, requiring clinical intervention as assessed by the investigator; or combined with moderate or greater amounts of pericardial effusion and clinical symptoms.
16. Pregnant or lactating women.
17. Subjects who, in the judgment of the investigator, have a history of other serious systemic disease or are unfit to participate in this trial for any other reason (the presence of psychiatric disorders, alcohol, drug, or substance abuse in the patient that may affect compliance with the trial, etc.)