Safety, Tolerability, and Preliminary Antitumor Activity of Novel Therapeutic Tumor Vaccines in Advanced Solid Tumors
Advanced solid tumors remain a major therapeutic challenge due to their complex heterogeneity and the immunosuppressive tumor microenvironment (TME). Although cancer vaccines are designed to induce long-lasting antitumor immunity, their efficacy is often limited by the TME's immune-evasive mechanisms. Building on this rationale, investigators developed a novel vaccine comprising irradiated tumor cells and stromal cells isolated from adjacent non-cancerous tissues or tumor tissues in combination with adjuvant. Irradiated tumor cells in vaccines such as YMN102, YMN103, YMN104, YMN105, YMN106, and YMN107 are transfected with GM-CSF; the others, such as YMN101 and YMN108, are not transfected with GM-CSF. Preclinical studies across multiple tumor models have demonstrated potent antitumor activity with no significant toxicity observed following administration. This first-in-human Phase I study is designed to evaluate the safety and tolerability of this irradiated vaccine in patients with advanced solid tumors, alongside a preliminary assessment of its antitumor activity and immunogenic profile. This is a first-in-human, Phase I, open-label study designed to evaluate the safety and tolerability of this novel vaccine. The study includes multiple arms targeting specific malignancies, including osteosarcoma, pancreatic cancer, HNSCC, colorectal cancer, HCC, glioma, and TNBC. The primary objective is to determine the incidence of dose-limiting toxicities (DLTs). Secondary objectives include assessing the objective response, progression-free survival (PFS), and overall survival (OS) per RECIST v1.1. Exploratory analyses will monitor dynamic changes in circulating biomarkers and intratumoral immune modulation to identify potential predictive markers of clinical response.
• Histologically or cytologically confirmed advanced solid tumors, or radiologically diagnosed HCC, eligible for one of the following study parts based on tumor type, clinical status, and prior treatment history:
• Part A1: Patients with advanced osteosarcoma who achieved Stable Disease (SD) or Partial Response (PR) following first-line chemotherapy, and have at least one remaining lung metastatic lesion \>= 0.5 cm.
• Part A2: Patients with advanced osteosarcoma who have relapsed, metastasized, or progressed following prior chemotherapy, or who are intolerant to the toxicities of previous systemic therapy.
• Part B1: Patients with advanced pancreatic cancer and disease progression following \>= 1 prior line of standard systemic therapy.
• Part C1: Patients with advanced HNSCC and disease progression following \>= 2 prior lines of systemic therapy.
• Part D1: Patients with advanced colon cancer and disease progression following \>= 3 prior lines of therapy (including fluoropyrimidine, oxaliplatin, and irinotecan). Patients with RAS wild-type must have received EGFR inhibitors.
• Part E1: Patients with advanced hepatocellular carcinoma (HCC) and disease progression following \>= 2 prior lines of systemic therapy.
• Part F1: Patients with advanced glioma and disease progression following the first-line Stupp regimen.
• Part G1: Patients with advanced pancreatic cancer and disease progression following \>= 1 prior line of therapy.
• Part H1: Patients with advanced or recurrent metastatic breast cancer who have progressed on or after \>= 3 prior lines of systemic therapy.
• Age 18-75 years.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
• Life expectancy \> 3 months.
• Adequate organ function within 7 days prior to first dose, including:
• Hematologic: Hemoglobin (Hb) \>= 80 g/L; White Blood Cell count (WBC) \>= 3.0 x 10\^9/L; Platelet count (PLT) \>= 80 x 10\^9/L; Absolute Neutrophil Count (ANC) \>= 1.5 x 10\^9/L.
• Hepatic: Total bilirubin \<= 1.5 x ULN (\<= 3 x ULN for liver metastases or HCC); ALT and AST \<= 2.5 x ULN (\<= 5 x ULN for liver metastases or HCC).
• Renal: Creatinine clearance \> 60 mL/min (Cockcroft-Gault formula). Coagulation: International Normalized Ratio (INR) \<= 1.5 x ULN.
• At least one measurable or evaluable lesion per RECIST v1.1.
• Ability to understand and sign written informed consent and comply with study procedures.