This is a Phase I, single-arm, open-label, dose-escalation study in patients with stage II or III ovarian cancer after surgery. The study will evaluate the safety, tolerability, immune response, and preliminary clinical activity of NeoOVIV, a personalized mRNA-lipid nanoparticle vaccine, when given 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); d) Whole-exome sequencing (WES) combined with RNA sequencing confirms the presence of ≥ 5 "usable neoantigens" (defined as: HLA binding affinity IC50 < 500 nM, and transcript expression level of the mutant gene in transcripts per million (TPM) ≥ 1);
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 NeoOVIV
DrugParticipants will receive the personalized NeoOVIV mRNA-lipid nanoparticle vaccine at a dose of 25 μg, corresponding to an approximate injection volume of 0.2 mL, by intramuscular injection. Vaccination will start approximately 10 weeks after surgery. Each participant will receive 9 planned vaccine doses: 4 priming doses given once every 3 weeks during chemotherapy, followed by 5 booster doses given weekly at weeks 22, 23, 24, 25, and 26 after surgery. Standard adjuvant chemotherapy will start approximately 4 weeks after surgery according to current clinical guidelines. Tislelizumab will start approximately 10 weeks after surgery and will be given for 4 doses, generally 1 day before the corresponding chemotherapy cycle.
Medium dose NeoOVIV
DrugParticipants will receive the personalized NeoOVIV mRNA-lipid nanoparticle vaccine at a dose of 50 μg, corresponding to an approximate injection volume of 0.4 mL, by intramuscular injection. Vaccination will start approximately 10 weeks after surgery. Each participant will receive 9 planned vaccine doses: 4 priming doses given once every 3 weeks during chemotherapy, followed by 5 booster doses given weekly at weeks 22, 23, 24, 25, and 26 after surgery. Standard adjuvant chemotherapy will start approximately 4 weeks after surgery according to current clinical guidelines. Tislelizumab will start approximately 10 weeks after surgery and will be given for 4 doses, generally 1 day before the corresponding chemotherapy cycle.
High dose NeoOVIV
DrugParticipants will receive the personalized NeoOVIV mRNA-lipid nanoparticle vaccine at a dose of 100 μg, corresponding to an approximate injection volume of 0.8 mL, by intramuscular injection. Vaccination will start approximately 10 weeks after surgery. Each participant will receive 9 planned vaccine doses: 4 priming doses given once every 3 weeks during chemotherapy, followed by 5 booster doses given weekly at weeks 22, 23, 24, 25, and 26 after surgery. Standard adjuvant chemotherapy will start approximately 4 weeks after surgery according to current clinical guidelines. Tislelizumab will start approximately 10 weeks after surgery and will be given for 4 doses, generally 1 day before the corresponding chemotherapy cycle.
Incidence of Treatment-Emergent Adverse Events Assessed by CTCAE Version 5.0
Adverse events will be assessed according to CTCAE Version 5.0. The number and percentage of participants with treatment-emergent adverse events will be reported. The onset time, grade, duration, seriousness, relationship to study treatment, management, and outcome of adverse events will be documented. Events of special interest will include injection-site reactions, fever, fatigue, headache, immune-related adverse events, and serious organ toxicities.
Disease-Free Survival
Disease-free survival is defined as the time from the date of surgery to the first documented disease recurrence according to RECIST 1.1 or death from any cause, whichever occurs first.
Change in Tumor Marker CA125 Level
Serum CA125 levels will be measured during follow-up to evaluate changes from baseline after treatment.
Change in Tumor Marker HE4 Level
Serum HE4 levels will be measured during follow-up to evaluate changes from baseline after treatment.
Neoantigen-Specific T-Cell Response Rate Assessed by IFNγ ELISpot
Neoantigen-specific T-cell responses will be assessed using peripheral blood samples by ex vivo IFNγ ELISpot after stimulation with vaccine neoantigen peptide pools. The response rate will be calculated according to predefined positivity criteria.
Vaccine Preparation Time
Vaccine preparation time is defined as the time from tumor tissue collection to delivery of the personalized NeoOVIV vaccine to the study center.
Rate of Treatment Coordination Delay
Treatment coordination delay is defined as a delay of more than 6 weeks between vaccine initiation and the start of chemotherapy or PARP inhibitor therapy. The percentage of participants with treatment coordination delay will be reported.
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