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.
Female, aged between 18 and 75 years (inclusive) at the time of signing the written informed consent form (ICF)
Patients with histopathologically confirmed epithelial ovarian cancer (EOC), including: a) Patients with Stage II (Stage IIA/IIB, tumor confined to the pelvis with no extra-abdominal metastasis) or Stage III (Stage IIIA/IIIB/IIIC, tumor involving the serosal surface of intra-abdominal viscera or regional lymph node metastasis) disease, in accordance with the International Federation of Gynecology and Obstetrics (FIGO) 2014 Staging System; b) Have undergone cytoreductive surgery (CRS), with postoperative pathological confirmation of RO/R1 resection (R1 defined as microscopic residual tumor at the surgical margin ≤ 1 mm); c) Qualified tumor tissue obtained during surgery is available for neoantigen screening: ① Fresh tumor tissue ≥ 100 mg (collected on the day of surgery and immediately immersed in RNA stabilization reagent); or ② ≥ 5 unstained sections of formalin-fixed paraffin-embedded (FFPE) tissue (each with a thickness of 5 μm, tumor cellularity ≥ 30%, and no significant necrosis)
In accordance with the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, postoperative contrast-enhanced pelvic MRI/CT shows no macroscopic residual disease (R2 resection), and lung metastasis, liver metastasis, and bone metastasis are excluded;
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to 1 (0: Fully ambulatory, no restriction in daily activities; 1: Ambulatory and able to perform light physical activity, no significant fatigue or dyspnea), with an expected overall survival of ≥ 1 year;
Histopathologically confirmed non-epithelial ovarian cancer, including ovarian germ cell tumors (e.g., teratoma, yolk sac tumor), sex cord-stromal tumors (e.g., granulosa cell tumor), and metastatic ovarian tumors (e.g., Krukenberg tumor metastatic to the ovary from the gastrointestinal tract);
R2 resection (macroscopic residual disease) after cytoreductive surgery, or postoperative imaging (contrast-enhanced pelvic MRI/CT, chest CT) showing distant metastasis (e.g., lung, liver, brain metastasis), or FIGO stage IV disease;
Prior treatment with any therapeutic cancer vaccine (e.g., peptide vaccine, DNA vaccine, other mRNA vaccines); or prior use of immune checkpoint inhibitors (e.g., anti-PD-1/PD-L1 antibodies, anti-CTLA-4 antibodies) with the last dose administered ≤ 30 days before enrollment;
Severe surgery-related complications within 4 weeks postoperatively, including but not limited to: intra-abdominal infection requiring intravenous antibiotics for ≥ 7 days, enteric fistula requiring surgical repair, massive hemorrhage requiring transfusion ≥ 400 mL within 24 hours, severe adhesive intestinal obstruction requiring gastrointestinal decompression for ≥ 3 days;
Single group
Low Dose
DrugParticipants will receive the NeoOVSV mRNA-lipid nanoparticle vaccine at a dose of 25 μg, corresponding to an approximate injection volume of 0.2 mL, administered by intramuscular injection. Vaccination will start approximately 4 weeks after surgery. The vaccine schedule includes 6 priming doses given once every 3 weeks during adjuvant chemotherapy, followed by 3 booster doses given once weekly after chemotherapy. Standard adjuvant chemotherapy will also start approximately 4 weeks after surgery according to current clinical guidelines, such as paclitaxel plus carboplatin. Tislelizumab will be administered for 6 doses, generally 1 day before chemotherapy.
middle dose
DrugParticipants will receive the NeoOVSV mRNA-lipid nanoparticle vaccine at a dose of 50 μg, corresponding to an approximate injection volume of 0.4 mL, administered by intramuscular injection. Vaccination will start approximately 4 weeks after surgery. The vaccine schedule includes 6 priming doses given once every 3 weeks during adjuvant chemotherapy, followed by 3 booster doses given once weekly after chemotherapy. Standard adjuvant chemotherapy will also start approximately 4 weeks after surgery according to current clinical guidelines, such as paclitaxel plus carboplatin. Tislelizumab will be administered for 6 doses, generally 1 day before chemotherapy.
high dose
DrugParticipants will receive the NeoOVSV mRNA-lipid nanoparticle vaccine at a dose of 100 μg, corresponding to an approximate injection volume of 0.8 mL, administered by intramuscular injection. Vaccination will start approximately 4 weeks after surgery. The vaccine schedule includes 6 priming doses given once every 3 weeks during adjuvant chemotherapy, followed by 3 booster doses given once weekly after chemotherapy. Standard adjuvant chemotherapy will also start approximately 4 weeks after surgery according to current clinical guidelines, such as paclitaxel plus carboplatin. Tislelizumab will be administered for 6 doses, generally 1 day before chemotherapy.
safety assessment
According to CTCAE Version 5.0, from the first dose administration to the last follow-up (18 months), the time of onset, grade, duration and management of adverse events (AEs) shall be documented, with special attention to:Local reactions: redness, swelling and pain at the injection site (assessed once weekly);Systemic reactions: fever (to be documented if ≥ 38.5°C), fatigue, headache (monitored daily within 72 hours after each dose);Immune-related adverse events (irAEs): thyroid dysfunction (thyroid function tested every 4 weeks), rash, enterocolitis (assessed whenever symptoms occur).
Disease-Free Survival (DFS)
Time from date of surgery to first recurrence (per RECIST 1.1 on contrast-enhanced pelvic MRI/CT) or death from any cause. Tumour evaluation every 3 months; tumour markers (CA125, HE4) measured every 4 weeks.
Immunogenicity assessment
Neoantigen-specific immune responses will be assessed using peripheral blood samples. T-cell responses will be evaluated by ex vivo IFNγ ELISpot after stimulation with vaccine neoantigen peptide pools, with response rates calculated based on predefined positivity criteria. Flow cytometry will assess CD8+ T-cell function, proliferation, and polyfunctional T-cell subsets. Single-cell RNA sequencing will be performed on purified T cells after vaccine priming. T-cell clonal expansion and persistence will be assessed by TCR sequencing, including tracking of vaccine-specific clones for up to 12 months. Neoantigen-specific B-cell responses will be evaluated by BCR sequencing of CD19+ B cells isolated from PBMCs, with analysis of vaccine-specific B-cell clonal expansion and persistence for up to 12 months.
12-month and 24-month DFS rates
Proportion of patients who remain free of disease at 12 and 24 months after surgery.
Minimal Residual Disease (MRD) Clearance
Clearance status of peripheral blood ctDNA using the MSK-ACCESS assay (high-depth sequencing covering 129 cancer-related genes). Result reported as "Detected" or "Not Detected".
Vaccine preparation time
Time from tumour tissue collection to delivery of the personalised vaccine to the study centre. Completion within 4 weeks is considered acceptable.
Vaccine treatment completion rate
Proportion of patients who complete all 9 planned vaccine doses. ≥80% is considered acceptable.
On-schedule PD-1 antibody administration rate
Proportion of PD-1 antibody doses given within the protocol-specified time window (no delay). ≥90% on-schedule rate is acceptable.
Interval between vaccine initiation and start of chemotherapy or PARP inhibitor
Time interval from the first vaccine dose to the first dose of chemotherapy or PARP inhibitor. An interval ≤6 weeks is acceptable.
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