A Single-Arm, Open-Label, Prospective Study Evaluating the Safety, Tolerability, and Immunogenicity of the NeoOVSV Vaccine in Patients With Ovarian Cancer After Surgery

\*\*Study Overview\*\* This is a Phase I, single-arm, open-label, prospective, non-randomized, single-center dose-escalation study. The study will evaluate the safety, tolerability, and preliminary activity of the NeoOVSV mRNA-lipid nanoparticle vaccine in patients with stage II/III ovarian cancer after surgery, in combination with standard adjuvant chemotherapy and a PD-1 antibody. \*\*Study Population\*\* Eligible participants are patients with FIGO 2014 stage II or III ovarian cancer who have undergone R0 or R1 surgical resection and have not yet started other adjuvant therapy within 4 weeks after surgery. \*\*Dose-Escalation Design\*\* The study uses a traditional "3+3" dose-escalation design. Three dose levels of the NeoOVSV vaccine will be tested: * Dose Level 1: 25 μg * Dose Level 2: 50 μg * Dose Level 3: 100 μg Each dose level will initially include 3 participants. If no participant develops dose-limiting toxicity (DLT) within 28 days after the first vaccination, the study will proceed to the next dose level. If 1 of 3 participants develops DLT, 3 additional participants will be enrolled at the same dose level. If 2 or more participants at a dose level develop DLT, dose escalation will stop, and the previous dose will be considered the maximum tolerated dose within the planned dose range. If no maximum tolerated dose is reached after evaluation of the 100 μg dose level, 100 μg will be considered the highest tested dose. The recommended dose for future studies will be selected based on overall safety, tolerability, immune response, feasibility, and clinical findings. \*\*Treatment Plan\*\* Participants will receive standard adjuvant chemotherapy, a PD-1 antibody, and the NeoOVSV vaccine. Standard chemotherapy will start approximately 4 weeks after surgery, according to current clinical guidelines. Tislelizumab, a PD-1 antibody, will also start approximately 4 weeks after surgery and will be given for 6 doses, usually before chemotherapy. The NeoOVSV vaccine will be given by intramuscular injection. The preferred injection site is the deltoid muscle of the upper arm. Other suitable intramuscular injection sites may be used when needed. The vaccine schedule includes: * \*\*Priming phase:\*\* 1 injection every 3 weeks during chemotherapy, for a total of 6 doses * \*\*Booster phase:\*\* 1 injection every week after chemotherapy, for a total of 3 doses Each participant will receive only one assigned vaccine dose level. \*\*Study Vaccine\*\* NeoOVSV is a shared-antigen mRNA-lipid nanoparticle vaccine. It contains mRNA sequences encoding seven ovarian cancer-associated antigens: FOLR1, MUC16, CLDN6, MSLN, WT1, PRAME, and MAGEA4. The mRNA is formulated in lipid nanoparticles to protect the mRNA and support delivery to immune cells. The vaccine will be manufactured and released according to GMP quality standards before use in the study. \*\*Main Study Assessments\*\* The primary objective is to assess safety and tolerability. Adverse events will be monitored and graded according to CTCAE v5.0. The study will closely monitor injection-site reactions, fever, fatigue, headache, and immune-related adverse events such as rash, thyroid dysfunction, colitis, pneumonitis, or myocarditis. DLT will be assessed during the first 28 days after vaccination. DLT may include severe treatment-related toxicity, grade 4 adverse events, serious organ toxicity, or adverse events that cause treatment interruption. Secondary and exploratory assessments include immune response, preliminary clinical activity, and feasibility. Blood samples will be collected at planned time points to evaluate vaccine-induced T-cell and B-cell responses using assays such as IFNγ ELISpot, flow cytometry, single-cell RNA sequencing, TCR sequencing, and BCR sequencing. Preliminary clinical activity will be assessed by disease-free survival, imaging, tumor markers such as CA125 and HE4, and circulating tumor DNA testing for minimal residual disease. Feasibility will be evaluated by vaccine production and release time, cold-chain delivery, treatment completion rate, and coordination with chemotherapy and other adjuvant treatments. \*\*Sample Size and Statistical Analysis\*\* The planned sample size is 9 to 18 participants, based on the 3+3 dose-escalation design. This Phase I study is not designed to test treatment superiority or non-inferiority. Safety, tolerability, immune response, disease-free survival, minimal residual disease clearance, and feasibility outcomes will mainly be summarized descriptively. All participants who receive at least one vaccine dose will be included in the safety analysis. Immune and clinical outcomes will be analyzed in the relevant evaluable populations. Kaplan-Meier methods may be used to describe disease-free survival, and exploratory statistical methods may be used to evaluate associations between immune responses and clinical outcomes. Participants will be followed after treatment to record survival status and long-term adverse events until death, study closure, or the end of follow-up, whichever occurs first.