A Study of FG-B901 Monotherapy or Combination With Chemotherapy in Advanced or Metastatic Solid Tumors

An Open-Label, Multicenter Phase I/II Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of FG-B901 Injection as Monotherapy and in Combination With Standard or Investigator-Determined Chemotherapy in Subjects With Unresectable Locally Advanced or Metastatic Solid Tumors

FG-B901 is a recombinant humanized IgG2 bispecific antibody targeting PD-L1 and CD40. It is designed to provide PD-L1-dependent CD40 agonism, thereby enhancing selectivity for the tumor microenvironment and reducing systemic toxicity compared with conventional CD40 agonists. Preclinically, FG-B901 promotes antigen-presenting cell activation and synergizes with PD-L1/PD-1 blockade to potentiate T-cell anti-tumor immunity. This is an open-label, multicenter phase I/II trial in subjects with unresectable locally advanced or metastatic solid tumors. The primary objectives are to evaluate the safety, tolerability, and pharmacokinetics of FG-B901 as monotherapy and in combination with chemotherapy. Secondary objectives include preliminary anti-tumor efficacy (e.g., objective response rate, disease control rate, progression-free survival, and overall survival).

Inclusion Criteria:

• Voluntarily sign the informed consent form, understand the study, are willing to comply with and have the ability to complete all trial procedures;
• Age 18-75 years (inclusive), any gender;
• Have histologically or cytologically confirmed locally advanced or metastatic solid tumors, and have failed standard therapy, or are intolerant to standard therapy, or for whom standard therapy is not available;
• Able to provide tumor tissue specimens and peripheral blood samples that meet testing requirements, or provide prior test reports that meet the requirements;
• ECOG performance status of 0 or 1;
• Expected survival ≥3 months;
• Have at least one measurable tumor lesion according to RECIST 1.1 criteria;
• Adequate cardiac, bone marrow, liver, renal function;

Exclusion Criteria:

• Have received a live vaccine within 3 months prior to randomization;
• Have received radiotherapy within 4 weeks prior to randomization;
• Have received other anti-tumor drug therapy within 4 weeks or within 5 half-lives of the anti-tumor drug prior to randomization;
• Have undergone major surgery within 4 weeks prior to randomization;
• Have received any clinical study drug treatment within 4 weeks prior to randomization;
• Have undergone major surgery within 4 weeks prior to randomization;
• Have a history of other (non-study tumor) malignancies within 3 years prior to randomization;
• Have received any organ transplant or bone marrow transplant;
• Have previously received any tumor necrosis factor receptor (TNFR) agonist antibody therapy, such as anti-CD40, anti-OX40, anti-CD137, anti-CD27, anti-CD357 antibodies, etc;
• Have experienced Grade ≥3 immune-related adverse events (irAEs) from prior immunotherapy;
• Have a history of severe allergic reactions or are allergic to the investigational drug (FG-B901);
• Have a history of central nervous system metastases and/or carcinomatous meningitis;
• Have adverse reactions from prior treatments that have not recovered to CTCAE v5.0 Grade ≤1 (excluding alopecia and anemia) prior to randomization;
• Have a history of severe respiratory disease;
• Have experienced a clinically significant cardiac disease within 6 months before the first dose of study drug;
• Have uncontrolled systemic diseases assessed by the investigator, including diabetes, hypertension, pulmonary fibrosis, interstitial lung disease, etc.;
• The investigator judges the subject to have obvious active gastrointestinal bleeding;
• Known history of Hepatitis C or chronic active Hepatitis B;
• Have experienced systemic treatment with corticosteroids within ≤2 weeks prior to randomization;
• Any other condition of the subject (e.g., psychological, geographical, or medical condition) that does not permit compliance with the study and follow-up procedures;
• Are pregnant or breastfeeding;