A Phase 3 Study of Manganese-primed Immunochemotherapy in Patients With Advanced Ovarian Cancer

Inclusion criteria

• Patients with histologically or cytologically confirmed epithelial ovarian cancer, primary fallopian tube cancer, or peritoneal cancer.
• Patients who have received at least two prior lines of systemic therapy, including at least one platinum-based regimen.
• Patients who experienced disease progression during or within 6 months after completion of the most recent line of systemic therapy.

Note: This most recent therapy is not required to be platinum-based and may be any systemic treatment (chemotherapy, targeted therapy, or other anticancer therapy).

• Patients with at least one measurable lesion.
• Patients who have received immunotherapy (anti-PD-1 antibodies, anti-PD-L1 antibodies), or bevacizumab, are not restricted from enrollment.
• Expected survival of more than 6 months.
• Age over 18 years.
• Patient weight > 40 kg.
• ECOG performance status ≤ 2.
• Peripheral blood white blood cell count > 3.5×10 /L.
• Bone marrow reserve and liver and kidney function (the following laboratory tests should be performed before initial treatment to prove):

• Absolute neutrophil count (ANC) ≥ 1,000/mm ;
• Hemoglobin > 80 g/dL;
• Platelet count > 80,000/mm ;
• ALT/AST < 3×ULN;
• Serum creatinine < 3×ULN;
• Total bilirubin level < 3×ULN.
• No significant hereditary diseases.
• Normal liver and kidney biochemical indicators.
• Completed the last systemic anticancer therapy at least 4 weeks prior to enrollment, with resolution of all treatment-related adverse events to grade ≤1 according to NCI-CTCAE v5.0, with the exception of alopecia and other clinically insignificant toxicities deemed acceptable by the investigator.
• No treatment with paclitaxel (albumin-bound) plus platinum in the past 3 months.
• Voluntary participation and signing of informed consent, compliance with the trial treatment plan and visit schedule, and cooperation in observing adverse events and efficacy.

Exclusion criteria

• Absolute neutrophil count (ANC) < 1×10 /L or platelets < 80×10 /L or hemoglobin < 80 g/dL (according to the normal values of the clinical trial center）.
• Serum total bilirubin levels higher than 3 times the upper limit of the reference range.
• ALT, AST, or ALP levels higher than 3 times the upper limit of the reference range when there are no liver metastases; ALT, AST, or ALP levels higher than 5 times the upper limit of the reference range when there are liver metastases.
• Patients receiving known strong inhibitors (e.g., ketoconazole) or inducers (e.g., rifampicin or St. John's Wort) of CYP3A4, or strong inhibitors (e.g., gemfibrozil) or inducers of CYP2C8; patients receiving treatment with potent P-gp inhibitors or inducers, or patients who cannot stop treatment with these agents for 2 weeks before the start of the study.
• Subjects' bowel obstruction or requirement for bowel obstruction-related interventions within 3 weeks prior to first study drug administration; subjects with incomplete bowel obstruction who have returned to normal within 1 month before the first dose of the experimental drug can be included in the study after discussion by the researchers.
• Patients with severe or uncontrolled ascites, defined as either of the following: a) symptomatic ascites corresponding to CTCAE ≥ Grade 2; b) history of therapeutic paracentesis for ascites within 3 weeks prior to enrollment.
• Organ failure:

• Heart: Grade III or IV.
• Liver: Grade C according to Child-Pugh B liver function classification.
• Kidney: Renal failure and uremia.
• Lung: Severe respiratory failure symptoms.
• Brain: Consciousness disorders.
• T-cell tumors such as T-cell lymphoma or T-cell leukemia.
• Major surgery within 4 weeks before enrollment, or planned major surgery during the study (excluding diagnostic surgery).
• HIV antibody positive, or other acquired, congenital immunodeficiency diseases, or patients with a history of organ transplantation.
• History of Parkinson's disease or epilepsy, or occurrence of diseases that can induce seizures within 12 months before the study (including a history of transient ischemic attack, stroke, traumatic brain injury with consciousness disorders).
• CTCAE grade 2 infections that do not respond to treatment or active clinically serious infections with CTCAE > Grade 2.
• Patients with active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection requiring treatment.
• Patients with a history of allergic reactions to study drug components or suspected allergies.
• Chronic diseases requiring immunotherapy or hormone therapy.
• Patients who have received any investigational drug treatment within 30 days before the first dose of the trial drug.
• Subjects with symptoms of brain or leptomeningeal metastasis.
• Subjects with a history of malignant tumors (non-study tumor) within 3 years before the first dose of the trial drug.
• History of the following diseases: interstitial lung disease, non-infectious pneumonia, or uncontrolled systemic diseases including diabetes, hypertension, pulmonary fibrosis, acute lung disease, abdominal infection, etc.