A Dose Ascending, Open Phase Ib/IIa Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of VG161 Combined With Nivolumab Injection in Subjects With Metastatic Gastric Cancer
VG161 is a recombinant human-IL12/15/PDL1B oncolytic HSV-1 injection. This study will be conducted in combination with nivolumab injection in HSV seropositive subjects with advanced metastatic gastric or gastroesophageal junction adenocarcinoma who have previously received two or more systemic treatment regimens (which must include anti-PD-1 monoclonal antibodies). This is an open-label study divided into two parts. Part 1: This part is an escalating dose trial to explore the safety of the combination and determine the recommended safe dose of the combination. Part 2: This part is an extension trial to investigate the preliminary efficacy of the combination at a safe dose.
‣ \- (Subjects must meet all of the following inclusion criteria to enter the trial)
• Subjects must give informed consent to this study before the trial and voluntarily sign a written informed consent form.
• aged 18 to 75 years (inclusive), male or female.
• Patients with advanced metastatic gastric or gastroesophageal junction adenocarcinoma confirmed by histopathology or cytology.
• According to the Guidelines for the Diagnosis and Treatment of Gastric Cancer (CSCO, version 2021), patients must have previously failed two or more systemic treatment regimens (which must include anti-PD-1 monoclonal antibodies), or patients who cannot continue treatment due to severe adverse reactions as judged by the investigator.
• Be able to provide paraffin blocks and/or tissue sections of previously archived pathological tissues, or willing to undergo tumor tissue biopsy before administration.
• The presence of at least one measurable CT scan according to RECIST 1.1 and meeting the requirements for an acceptable injection dose volume (or the first injection dose volume in Phase IIa) in the current dose group, tumor metastases that can be injected under ultrasound guidance (injected lesions are best major tumor burden lesions), and the baseline longest diameter of the injected lesion (lymph node lesions are short diameters) \> 1.5 cm.
• Positive test result for herpes simplex virus I antibodies (HSV-1 IgG or HSV-1 IgM).
• ECOG performance status score 0-1.
• Expected survival time of more than 3 months.
⁃ adequate organ function: 1) blood routine (no blood transfusion or colony-stimulating factor treatment within 14 days): ANC ≥ 1.5 × 10\^9/L, PLT ≥ 100 × 10\^9/L, Hb ≥ 85 g/L, lymphocyte count ≥ 1.5 × 10\^9/L (for lymphocyte count 0.8 × 10\^9/L to 1.5 × 10\^9/L, the investigator judged whether to enroll); 2) liver function: TBIL ≤ 1.5 × ULN, ALT ≤ 3 × ULN, AST ≤ 3 × ULN; 3) renal function: Cr ≤ 1.5 × ULN, and creatinine clearance ≥ 45ml/min (calculated according to Cockcroft-Gault formula); 4) coagulation function: activated partial thromboplastin time (APTT) ≤ 1.5 × ULN, international normalized ratio (INR) ≤ 1.5 × ULN.
⁃ eligible subjects of childbearing potential (men and women) must agree to use a reliable method of contraception (hormonal or barrier method or abstinence) during the trial and for at least 90 days after the last dose (VG161 or nivolumab, calculated at the later of the day).
⁃ Female patients of childbearing age must have a negative blood pregnancy test within 1 day prior to enrollment.