The Safety and Clinical Efficacy of RAK Cell Therapy in Late-stage Gastric Cancer: A Randomized Controlled Trial

• RetroNectin active Killer cells (Biological): RetroNectin-Activated Killer (RAK) cells, derived from autologous peripheral blood mononuclear cells (PBMCs), are induced in vitro by RetroNectin along with anti-CD3 monoclonal antibody and Interleukin-2 (IL-2). These cells consist of various cytotoxic effectors, primarily CD8+ T (cytotoxic T, Tc) cells and natural killer T cells, which exhibit minimal cytotoxicity to normal cells but substantial specificity to tumor cells, thereby demonstrating both safety and potent anti-tumor activity.
• TAS-102 (trifluridine and tipiracil, Lonsurf®) (Drug): Based on the results of the RECOURSE \[16\] and TERRA \[17\] studies, TAS-102 (Trifluridine/Tipiracil Hydrochloride) will be administered orally at a dose of 35mg/m², twice daily, Days 1-5, with each cycle lasting 3 weeks.

Primary outcomes

• Progression-free survival [one-year]: Progression-Free Survival (PFS) is the length of time during and after treatment that a patient's cancer does not get worse. It measures how long the disease remains stable or in remission.

Secondary outcomes

• Overall Survival [one-year]: from a defined randomization until death from any cause.
• Objective Response Rate (ORR) [one-year]: the proportion of patients in a clinical trial whose cancer shrinks (responds) by a predefined amount for a minimum period of time. It is a direct measure of a drug's anti-tumor activity.
• Time to Progression (TTP) [one-year]: the length of time from the start of treatment (or randomization in a trial) until the patient's cancer is objectively documented to have worsened.

Other outcomes

• Biotherapy-related adverse reactions [one-year]: side effects caused by a class of cancer treatments known as Biological Therapies: Dermatitis: Skin rash and itching. Hepatitis: Inflammation of the liver, detected by elevated liver enzymes in blood tests. Pneumonitis: Inflammation of the lungs, causing cough, shortness of breath, and chest pain. This can be life-threatening. Endocrinopathies: Inflammation of hormone glands, leading to conditions like: Thyroiditis (underactive or overactive thyroid). Hypophysitis (inflammation of the pituitary gland). Adrenal Insufficiency (where the body can't manage stress). Less Common but Serious: Can affect almost any organ, including the heart (myocarditis), muscles (myositis), kidneys (nephritis), and nervous system (neuropathy).
• Blood immunology indicators [one-year]: T-cell count, IL-2/IL-6/IL-11, TGF-β,

Sex: All, ages: 18 Years to 70 Years

Inclusion Criteria:

* 1\. Subjects voluntarily join this study and sign the informed consent form. 2. Age ≥18 years and ≤70 years. 3. Confirmed by gastroscopic pathology or imaging (enhanced CT/PET-CT) as Stage IV gastric cancer or gastroesophageal junction adenocarcinoma (cTanyNanyM1). Metastatic sites include but are not limited to: liver, peritoneum, lungs, pancreas, greater omentum, retroperitoneal lymph nodes, etc.

  4\. Failure or disease progression after prior frontline anti-tumor therapy (including ineffective first- and second-line chemotherapy, targeted therapy, and immunotherapy for advanced gastric cancer).

  5\. Have measurable solid tumors (efficacy evaluation standard: RECIST 1.1); tumor assessment via CT scan or MRI must be performed within 28 days before treatment.

  6\. Physical performance status ECOG 0-3. 7. Expected lifespan ≥1 month. 8. Participants must be able to understand the study procedures and agree to participate in the study by providing written informed consent.

Exclusion Criteria:

* 1\. Concurrent other types of malignancy. 2. Severe cardiac, pulmonary, or cerebral system diseases. 3. Expected survival <1 month. 4. Laboratory investigations indicating unsuitability for receiving anti-tumor biotherapy:

  1. Moderate to severe bone marrow suppression: (HGB <80 g/L; WBC <2.0×10⁹/L; ANC <1.0×10⁹/L; PLT <50×10⁹/L).
  2. Significantly decreased liver function (Child-Pugh Grade C).
  3. Severe renal insufficiency (CKD Stage III and above).
  4. Severe coagulation dysfunction (INR ≥1.5 or APTT >1.5 × ULN).

• Study Protocol and Statistical Analysis Plan (PDF, 2025-06-30)