PRaG-1 Plus PRaG Therapy in Advanced Solid Tumors: A Prospective Clinical Trial (PRaG 10.0)

Inclusion Criteria:

1. Age ≥ 18 years.
2. Histologically confirmed treatment-naïve or relapsed/metastatic advanced solid malignancies with no standard treatment option per current clinical guidelines or intolerance to standard therapy; measurable metastatic lesions ≥1 cm (by RECIST criteria); absolute lymphocyte count (ALC) below lower limit of normal (LLN).
3. No history of congestive heart failure, unstable angina, or unstable cardiac arrhythmias within the past 6 months.
4. ECOG performance status 0-3; estimated life expectancy ≥3 months.
5. No history of significant hematologic, cardiac, pulmonary, hepatic, or renal dysfunction.
6. Baseline AST ≤3×ULN and ALT ≤3×ULN (≤5×ULN for hepatocellular carcinoma or liver metastases); creatinine ≤3×ULN.
7. Capacity to comprehend study procedures and voluntarily provide written informed consent.

Exclusion Criteria:

1. History of other malignancies within the past 5 years, except for adequately treated non-melanoma skin cancer or cervical carcinoma in situ.
2. Uncontrolled epilepsy, central nervous system disorders, or psychiatric disorders that, in the investigator's judgment, may interfere with informed consent or treatment adherence.
3. Clinically significant active cardiac disease, including symptomatic coronary artery disease, NYHA Class II or higher congestive heart failure, severe arrhythmias requiring pharmacological intervention, or myocardial infarction within the past 12 months.
4. History of solid organ transplant requiring ongoing immunosuppressive therapy.
5. Known significant active infection, or significant hematologic, renal, metabolic, gastrointestinal, or endocrine dysfunction, or other serious uncontrolled comorbidities as determined by the investigator.
6. Allergy to any component of the study drug(s).
7. History of immunodeficiency, including HIV infection, acquired or congenital immunodeficiency disorders, solid organ transplant, or chronic immunosuppressive therapy for immune-related conditions.
8. Active or latent tuberculosis infection confirmed by positive T-SPOT.TB test or chest X-ray findings suggestive of tuberculosis.
9. Any other condition that, in the investigator's clinical judgment, may compromise study participation or safety.