QL1706-Based Therapy Post-PD-1/L1 Failure in Advanced Endometrial Cancer

Inclusion Criteria:

1. Age ≥18 years and ≤70 years.

2. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

3. Recurrent or metastatic endometrial carcinoma, confirmed by pathology or imaging.

4. At least one measurable tumor lesion according to RECIST v1.1 criteria.

5. Patients must have received prior anti-PD-1/L1 monoclonal antibody (mAb) therapywith a progression-free survival (PFS) of ≥6 months; however, the last dose ofanti-PD-1/L1 mAb must have been administered at least 5 half-lives before theinitiation of the current treatment.

6. Patients who have received prior anti-angiogenic therapy are eligible, providedthere is a washout period of at least 5 half-lives before re-administration.

7. Patients who have failed ≤2 lines of prior systemic therapy are eligible (endocrinetherapy is not counted as a line of treatment).

8. All other anti-tumor therapies must be discontinued at least 4 weeks beforetreatment initiation. Patients taking hormonal medications require a 30-day washoutperiod.

9. Laboratory tests during the screening period must demonstrate adequate organfunction.

10. Female subjects of childbearing potential must have a negative serum pregnancy testwithin 3 days prior to the first dose. If a female subject of childbearing potentialengages in sexual activity with a non-sterilized male partner, the subject must usean acceptable and highly effective contraceptive method since screening and mustagree to continue such precautions until 6 months after the last dose of the studydrug; periodic abstinence and the rhythm method are not acceptable forms ofcontraception.

11. Voluntarily sign the informed consent form, understand the nature, purpose, andprocedures of the trial, and willingly comply with the trial requirements.

Exclusion Criteria:

1. Previous treatment with PD-1/CTLA-4 dual-target immunotherapy, immunecheckpoint agonists (e.g., ICOS, CD40, CD137, GITR, OX40 antibodies, etc.), orimmune cell therapy.

2. Discontinuation of anti-PD-1/PD-L1 antibody therapy due to related toxicity. 3.Presence of any active autoimmune disease or history of autoimmune disease (including but not limited to autoimmune hepatitis, interstitial pneumonia,uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism;patients with vitiligo or childhood asthma that has completely resolved andrequires no intervention in adulthood may be included; asthma requiringbronchodilator treatment is excluded).

3. Current use of immunosuppressants or systemic corticosteroids forimmunosuppression (dose >10 mg/day prednisone or equivalent) within 2 weeksprior to enrollment.

4. Known active tuberculosis (TB) or suspected active TB requiring clinicalevaluation for exclusion; known active syphilis infection.

5. History of allogeneic organ transplantation or allogeneic hematopoietic stemcell transplantation.

6. History of severe allergic reactions to monoclonal antibodies. 8. Known historyor evidence of interstitial lung disease or active non-infectious pneumonitis.

7. History or current presence of central nervous system (CNS) metastases.Baseline imaging to confirm the absence of brain metastases is not mandatory.Patients with unknown CNS status but clinical signs suggestive of CNSmetastases must be excluded via CT/MRI.

8. History of other malignancies (except non-melanoma skin cancer or cervicalcarcinoma in situ; patients with other prior malignancies must have beendisease-free for at least 3 years).

9. Uncontrolled hypertension despite antihypertensive therapy (systolic BP ≥140mmHg or diastolic BP ≥90 mmHg); hypertensive crisis or hypertensiveencephalopathy in the past.

10. History of unstable angina, myocardial infarction (MI), chronic heart failure (CHF), clinically significant arrhythmias requiring treatment (except stableatrial fibrillation), or left ventricular ejection fraction <50% within 6months before the first dose.

11. Current thrombolytic or anticoagulant therapy (prophylactic low-dose aspirin orlow molecular weight heparin is permitted).

12. Arterial/venous thrombotic events within 6 months before enrollment (e.g.,cerebrovascular accident, transient ischemic attack, cerebral hemorrhage,cerebral infarction, deep vein thrombosis, pulmonary embolism).

13. Major vascular disease within 6 months before study treatment (e.g., aorticaneurysm requiring surgical repair or recent peripheral arterial thrombosis).

14. Major surgery within 4 weeks before study treatment (excluding diagnosticprocedures) or anticipated major surgery during the study.

15. Prior radiotherapy (except palliative bone radiotherapy), chemotherapy, orsurgery (excluding biopsy) within 4 weeks before the first study dose; lastantibody dose <4 weeks before study treatment; molecular targeted therapy (including other investigational oral targeted agents) <5 half-lives beforestudy treatment; or unresolved toxicities (>CTCAE grade 1, except alopecia)from prior therapy.

16. Active infection, unexplained fever ≥38.5°C within 7 days before treatment, orbaseline white blood cell count >15×10⁹/L.

17. Congenital or acquired immunodeficiency (e.g., HIV infection); HBsAg-positivewith HBV DNA ≥2000 IU/mL, or HCV antibody-positive.

18. Live/attenuated vaccination within 4 weeks before study treatment oranticipated during the study.

19. Any other condition deemed by the investigator to potentially affect studyresults or lead to premature termination.

20. Pregnant or breastfeeding women.