An Open-label Study of SG1827 Combined With Anti-PD-1/PD-L1 Antibody and Bevacizumab in Patients With Advanced Solid Tumors

A Phase 1b/2 Clinical Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of SG1827 for Injection in Combination With Anti-PD-1/PD-L1 Antibody and Bevacizumab in Patients With Advanced Malignant Solid Tumors

This multicenter, open-label Phase Ib/II study with dose escalation and expansion in Chinese patients with advanced solid tumors consists of Part A (SG1827 plus anti-PD-1/PD-L1) and Part B (SG1827 plus anti-PD-1/PD-L1 and bevacizumab), both evaluating safety, tolerability, PK/PD, immunogenicity, and antitumor efficacy.

This study is a multicenter, open-label, Phase Ib/II clinical trial with dose-escalation and dose-expansion components, conducted in Chinese patients with advanced malignant solid tumors. In Part A, participants will receive SG1827 in combination with an anti-PD-1/PD-L1 antibody; in Part B, participants will receive SG1827 in combination with an anti-PD-1/PD-L1 antibody and bevacizumab. Part A is designed to evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics (PK/PD), immunogenicity, and anti-tumor efficacy of SG1827 plus an anti-PD-1/PD-L1 antibody in advanced solid tumors, while Part B is designed to evaluate the safety, tolerability, PK/PD, immunogenicity, and anti-tumor efficacy of SG1827 combined with an anti-PD-1/PD-L1 antibody and bevacizumab in the same patient population.

Inclusion Criteria:

1. Age ≥18 years, male or female.
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
3. Life expectancy ≥3 months.
4. Histologically or cytologically confirmed unresectable locally advanced or metastatic solid tumor. Participants enrolled in the dose escalation phase must have received prior systemic therapy, with disease progression or intolerance to the last line of treatment.
5. At least one measurable lesion per RECIST 1.1 criteria.
6. Adequate organ and bone marrow function.
7. Female participants of childbearing potential and male participants with partners of childbearing potential must use at least one accepted method of contraception during the study treatment period and for at least 5 months (150 days) after the last dose.
8. Male participants must refrain from sperm donation from the time of signing the informed consent form (ICF) until at least 5 months after the last dose.

Exclusion Criteria:

1. Prior treatment with immunotherapies targeting CTLA 4 and/or CD28 (or agents containing these targets).

2. Presence of active central nervous system (CNS) metastatic lesions.

3. Other malignant tumors within 5 years prior to the first dose.

4. Receipt of any of the following treatments or procedures:

   1. Major surgery (other than diagnostic biopsy) within 28 days prior to the first dose;
   2. Anti tumor macromolecular antibody therapy or other unmarketed investigational anti tumor therapies within 28 days prior to the first dose; anti tumor chemotherapy, endocrine therapy, or oral small molecule targeted therapy within 14 days prior to the first dose; traditional Chinese medicine preparations approved by the NMPA with anti tumor indications within 7 days prior to the first dose;
   3. Curative radiotherapy within 28 days prior to the first dose; palliative radiotherapy is permitted within 14 days prior to the first dose, provided that all related AEs have resolved to ≤ Grade 1 (CTCAE v6.0), except for toxicities such as alopecia that are judged by the investigator to have no safety risk and not to violate other inclusion/exclusion criteria;
   4. Vaccination with any live vaccine within 28 days prior to the first dose, or planned vaccination with any live vaccine during the study treatment period;
   5. History of allogeneic organ transplantation or allogeneic stem cell transplantation.

5. Use of systemic corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive agents within 14 days prior to the first dose or during the study period.

6. Active infection requiring intravenous or oral antibiotic therapy within 14 days prior to the first dose, with the exception of prophylactic use.

7. Severe cardiovascular or cerebrovascular disease within 6 months prior to the first dose.

8. Participants with active hepatitis B or hepatitis C, or human immunodeficiency virus (HIV) infection.

9. Known allergy to any component of the study drug, or history of Grade 3 4 allergic reactions to any biologic product, or history of life threatening hypersensitivity.

10. Immune related adverse reactions that led to permanent discontinuation of prior anti tumor immunotherapy.

11. Current or prior history of idiopathic pulmonary fibrosis or idiopathic pneumonia; current active pulmonary disease, interstitial lung disease or pneumonitis (excluding radiation induced localized interstitial pneumonia), pulmonary fibrosis, etc.; history of tracheal fistula; severe dyspnea, pulmonary insufficiency, or requiring continuous oxygen supplementation.

12. Uncontrolled pleural, peritoneal, or pericardial effusion requiring repeated drainage or with significant symptoms within 14 days prior to the first dose.

13. Psychiatric disorders or poor compliance.

14. Female participants who are pregnant or breastfeeding.

15. Any other condition that, in the investigator's opinion, would make the participant unsuitable for participation in the study.