| Eligibility |
Inclusion Criteria:
- Age =18
- Eastern Cooperative Oncology Group (ECOG) Performance Status (ECOG): 0-2. Expected
survival = 6 months.
- Patients with newly diagnosed International Federation of Gynecology and Obstetrics
(FIGO) 2009 stage III-IV endometrial cancer or recurrent endometrial cancer after = 1
line of platinum-based chemotherapy (including neoadjuvant, adjuvant, and concurrent
chemotherapy). For patients who have failed platinum-based chemotherapy, a
platinum-free interval of = 12 months is required.
- No restriction on pathological type, abnormal p53 expression indicated by
immunohistochemistry, and confirmation of TP53 gene mutation by Sanger sequencing or
next-generation sequencing (NGS).
- No prior treatment with immune checkpoint blockade (ICB) or poly (ADP-ribose)
polymerase inhibitor (PARPi).
- Discontinuation of previous radiation therapy, chemotherapy, or hormone therapy for at
least 4 weeks.
- Adequate organ function as follows (no use of drugs containing blood components or
corrective treatment with hematopoietic growth factors in the 7 days prior to
randomization): Aspartate Aminotransferase (AST) and Alanine Transaminase (ALT) = 2.5
times the upper limit of normal (= 5 times for patients with liver metastasis) and
total bilirubin = 1.5 times the upper limit of normal; serum creatinine = 1.5 times
the upper limit of normal; platelets = 90,000 cells/mm3, hemoglobin = 90 g/L, and
neutrophils = 1,500/mm3.
- Thyroid function prior to randomization: Thyroid-stimulating hormone (TSH) level = 1
times the upper limit of normal, or if TSH is not within the normal range, free T4 = 1
times the upper limit of normal.
- Peripheral neuropathy grade < 2 (Common Terminology Criteria for Adverse Events, CTCAE
5.0) before treatment.
- Signed informed consent and ability to provide tumor tissue samples from initial
diagnosis/recurrence for homologous recombination deficiency (HRD) testing.
- Willingness to comply with clinic visits and follow-up.
Exclusion Criteria:
- Currently participating in another clinical trial or within 4 weeks since completing
another clinical trial.
- Known allergy to any components of the investigational drug.
- Previous treatment with immune checkpoint inhibitors, including but not limited to
other anti-PD-1 and anti-PD-L1 antibodies.
- Patients requiring the use of immunosuppressive medications.
- Previous treatment with poly (ADP-ribose) polymerase inhibitors (PARPi).
- Patients requiring systemic or absorbable topical corticosteroids at an
immunosuppressive dose, or patients who have used prednisone or equivalent drugs at a
dose >10 mg/day in the two weeks prior to taking the study drug.
- Patients with any active autoimmune disease or a history of autoimmune diseases,
including but not limited to active hepatitis, pneumonia, uveitis, colitis
(inflammatory bowel disease), pituitary inflammation, vasculitis, nephritis,
hyperthyroidism, and hypothyroidism, excluding resolved childhood asthma/atopic
diseases and vitiligo. Patients with intermittent use of bronchodilators or other
medical interventions for asthma should also be excluded.
- Patients in the active infectious phase requiring antimicrobial treatment (e.g.,
antibiotics, antiviral drugs, antifungal drugs).
- History of immunodeficiency, including human immunodeficiency virus (HIV)
seropositivity or other acquired or congenital immunodeficiency diseases.
- Uncontrolled clinically significant cardiac symptoms or diseases within the past year,
including but not limited to New York Heart Association (NYHA) class II or higher
heart failure, unstable angina, myocardial infarction within the past year, atrial
fibrillation, clinically significant supraventricular or ventricular arrhythmias
requiring treatment or intervention, PR interval >250 ms, or QTc =470 ms.
- Arterial or venous thrombosis within the past 6 months.
- Poorly controlled hypertension (systolic blood pressure =140 mmHg and/or diastolic
blood pressure =90 mmHg) despite antihypertensive medication, proteinuria =(++) and
24-hour total urinary protein >1.0 g.
- Coagulation abnormalities (international normalized ratio [INR] >2.0, prothrombin time
[PT] >16s), bleeding tendency, or receiving thrombolytic or anticoagulant therapy.
- Patients with other malignant tumors within the past 5 years, excluding basal cell
carcinoma of the skin and squamous cell carcinoma of the skin.
- Vaccination with live vaccines within 4 weeks prior to the first administration of the
investigational drug. Note: Administration of inactivated seasonal influenza vaccines
is allowed.
- History of substance abuse with psychotropic drugs and unable to quit, or patients
with psychiatric disorders.
- The investigator believes that any other medical, psychiatric, or social factors may
affect the rights, safety, ability to sign informed consent, patient's completion of
the study, or interpretation of study results.
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