Inclusion Criteria:
1. Patients must receive have completed at least 1 but no more than 3 prior lines of therapy including at least one prior platinum-based chemotherapy:
* Patients with recurrent endometrial cancer that has failed at least one line of platinum-based chemotherapy;
* Patients with newly diagnosed advanced (metastatic and/or unresectable) disease has persist lesion after frontline treatment with surgery and platinum-based chemotherapy ± radiotherapy;
* Patients with newly diagnosed advanced disease that is not amenable to curative treatment with surgery and/or radiation therapy cannot tolerate chemotherapy;
2. Patients may have received prior hormonal therapy for treatment of endometrial carcinoma. All hormonal therapy must be discontinued at least one week prior to the first date of study therapy.
3. Histologically proven diagnosis of endometrial cancer.
4. Tumors must demonstrate MMRd and MLH1 methylation.
° Endometrial tumor MMR and MLH1 methylation status: All participants must be screened using Immunohistochemistry (IHC) for MMR proteins MLH1, MSH2, MSH6, and PMS2. MLH1 gene promoter methylation is performed in tumors exhibiting MLH1 and/or PMS2 IHC loss. MLH1 methylation status is determined by the bisulfite mediated detection of methylated cytosines, as described by Benhamida (Benhamida JK, et al. Reliable Clinical MLH1 Promoter Hypermethylation Assessment Using a High-Throughput Genome-Wide Methylation Array Platform. J Mol Diagn. 2020 Mar;22:368-375. doi: 10.1016/j.jmoldx.2019.11.005).
5. All patients must have measurable disease by RECIST 1.1.
6. ECOG performance status 0-2.
7. Life expectancy ≥ 12 weeks.
8. Patients must have adequate organ function:
* Absolute neutrophil count (ANC) ≥ 1.5×10\^9/L;
* Platelet count ≥ 70 × 10\^9/L;
* Hemoglobin ≥ 80 g/L;
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN);
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × ULN (however, patients with known liver metastasis who have AST or ALT level ≤ 5 × ULN may be enrolled);
* Creatinine ≤ 1.5 × ULN or creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula);
* Baseline albumin ≥ 25 g/L;
* Thyroid-stimulating hormone (TSH) levels ≤ 1 × ULN (however, patients with free Triiodothyronine \[FT3\] or free Thyroxine \[FT4\] levels ≤ 1 × ULN may be enrolled)
9. Signed and dated informed consent.
Exclusion Criteria:
1. Histologically confirmed diagnosis of sarcoma components including malignant mixed mullerian tumors.
2. Patients who have had prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune check point pathways.
3. History of severe hypersensitivity reaction (≥Grade 3) to any monoclonal antibody.
4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure and unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
5. Uncontrolled hypertension (blood pressure \>140/90 mmHg) after adequate treatment.
6. Central nervous system diseases, including uncontrollable epilepsy and central nervous system metastases.
7. Radiographically confirmed major blood vessel invasion/infiltration.
8. Prior chemotherapy, targeted small molecule therapy, bevacizumab, or radiation therapy within 4 weeks of study Day 1 or not recovered from adverse events caused by previously administered treatment.
9. Prior hormonal therapy for the treatment of endometrial carcinoma within 1 weeks of study Day 1.
10. Known history of Human Immunodeficiency Virus (HIV).
11. Known active tuberculosis (TB, Bacillus tuberculosis).
12. Known active Hepatitis B or C.
13. known active ulcer, or active colitis.
14. Received live vaccine within 30 days of planned start of study treatment.
15. Patients who have gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of anlotinib.
16. Patients who have severe gastrointestinal or non-gastrointestinal fistula (≥Grade 3).
17. Patients who have an allogenic tissue/solid organ transplant.
18. Patients who have a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \<10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
⁕⁕⁕Note:
* Topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption) are permitted;
* Physiologic replacement doses of systemic corticosteroids are permitted, even if \<10 mg/day prednisone equivalents are permitted;
* A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted;
19. Is pregnant or breastfeeding.
