Safety, Tolerability, and Preliminary Efficacy of Peginterferon α-2b in Combination With an Anti-PD-1 Antibody in Patients With Advanced or Metastatic Malignant Solid Tumors

An Open-Label, Dose-Escalation Clinical Study of Peginterferon Alfa-2b in Combination With an Anti-PD-1 Antibody to Evaluate the Safety, Tolerability, and Preliminary Efficacy in Patients With Advanced or Metastatic Malignant Solid Tumors

This study is an open-label, dose-escalation phase I clinical trial conducted in patients with advanced or metastatic solid tumors in China.This study is an open-label, dose-escalation phase I clinical trial conducted in patients with advanced or metastatic solid tumors in China. The aim is to evaluate the safety, tolerability and preliminary efficacy of pegylated interferon alpha-2b (Peg-IFNα2b) combined with PD-1 monoclonal antibody.

The aim is to evaluate the safety, tolerability and preliminary efficacy of pegylated interferon alpha-2b (Peg-IFNα2b) combined with PD-1 monoclonal antibody.

The study adopts the classic "3+3" dose escalation design and plans to enroll approximately 60 patients.The study adopts the classic "3+3" dose escalation design and plans to enroll approximately 60 patients. The first part is the dose escalation stage, aiming to determine the maximum tolerated dose (MTD) or the recommended phase II dose (RP2D) for the combined treatment. The first part is the dose escalation stage, aiming to determine the maximum tolerated dose (MTD) or the recommended phase II dose (RP2D) for the combined treatment. The second part is the expansion stage, where the efficacy signals will be further observed at the selected dose. The second part is the expansion stage, where the efficacy signals will be further observed at the selected dose. The primary endpoints are treatment-related adverse events and dose-limiting toxicities (DLT), while the secondary endpoints include objective response rate (ORR), progression-free survival (PFS), etc. The primary endpoints are treatment-related adverse events and dose-limiting toxicities (DLT), while the secondary endpoints include objective response rate (ORR), progression-free survival (PFS), etc. The study period is planned to be 12 months. The study period is planned to be 12 months.

Inclusion Criteria:

• 1. Understand and voluntarily sign the informed consent form (ICF). 2. Aged ≥18 years and ≤75 years. 3. Histologically, cytologically, or radiologically confirmed diagnosis of advanced or metastatic malignant solid tumor, with prior standard treatment failure, no standard treatment available, or intolerance to standard treatment.

  4. At least one measurable lesion per RECIST v1.1, confirmed by computed tomography (CT) and/or magnetic resonance imaging (MRI).

  5. Absolute Monocyte Count (AMC) <0.25×10^9/L (tested by local lab; one retest is allowed if screening AMC is between 0.25-0.35×10^9/L).

  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Life expectancy ≥3 months. 8. Adequate organ function within 1 week prior to first study drug administration (no transfusion or blood products, no hematopoietic growth factors for correction within 14 days prior to screening):

• Hematology: White blood cell count ≥3.0×10^9/L, Absolute Neutrophil Count (ANC) ≥1.5×10^9/L, Platelet count ≥50×10^9/L, Hemoglobin ≥90 g/L.

• Hepatic: Serum total bilirubin ≤1.5×ULN (≤3×ULN for Gilbert's syndrome); AST and ALT ≤2.5×ULN (≤5×ULN for liver metastases); Alkaline phosphatase (ALP) ≤2×ULN (≤5×ULN for bone or liver metastases).

• Renal: Urea/BUN and serum creatinine ≤1.5×ULN OR creatinine clearance ≥50 mL/min (Cockcroft-Gault formula).

• Coagulation: International Normalized Ratio (INR) and prothrombin time (PT) ≤1.5×ULN; activated partial thromboplastin time (APTT) ≤1.5×ULN.

  9. For women of childbearing potential: negative pregnancy test within 1 week prior to first dose. All subjects of childbearing potential and their partners must agree to use effective contraception during the study and for 6 months after the last dose.

  10. For subjects who are HBsAg positive and/or HBcAb positive: HBV DNA <2000 IU/mL, must continue or initiate anti-HBV therapy (e.g., entecavir, tenofovir disoproxil fumarate). For subjects who are HCV-Ab positive: HCV RNA below the lower limit of detection.

Exclusion Criteria:

• 1. History of another active malignancy within the past 5 years (except for cured malignancies like thyroid cancer, basal cell carcinoma, cervical carcinoma in situ).

  2. Clinically significant moderate to severe ascites. 3. History of gastrointestinal hemorrhage or definitive gastrointestinal bleeding tendency within 6 months prior to study treatment.

  4. Abdominal fistula, gastrointestinal perforation, or intraperitoneal abscess within 6 months prior to study treatment.

  5. Known hereditary or acquired bleeding or thrombotic tendency. 6. History of thrombosis or thromboembolic events within 6 months prior to study treatment.

  7. Poorly controlled cardiac clinical symptoms or disease. 8. Hypertension inadequately controlled by antihypertensive medication. 9. Factors affecting oral administration. 10. Prior or current central nervous system metastases. 11. HIV positive, tuberculosis positive, or co-infection with HBV and HCV. 12. Prior or planned organ or allogeneic bone marrow transplantation. 13. Interstitial lung disease that may interfere with the detection or management of suspected drug-related pulmonary toxicity.

  14. Known or suspected active autoimmune disease. 15. Requiring systemic treatment with corticosteroids or other immunosuppressants within 14 days prior to the first study treatment.

  16. Use of strong CYP3A4 inducers or inhibitors within 2 weeks prior to signing ICF.

  17. Known history of severe allergy to interferon, any monoclonal antibody, or cytidine nucleoside analogue antitumor drugs.

  18. Severe infection within 4 weeks prior to study treatment. 19. Palliative radiotherapy for non-target lesions is allowed but must be completed at least 2 weeks before study treatment.

  20. Treatment with another investigational drug within 28 days prior to study treatment.

  21. Major surgery or medical device treatment within 28 days prior to study treatment.

  22. Any other condition deemed by the investigator to be inappropriate for participation in this clinical trial.