A Study to Estimate Early Clinical Efficacy Signals of GLP-1 Agonist Administration in Conjunction With Levonorgestrel Intrauterine Device in Obese Patients With Endometrioid Intraepithelial Neoplasia

Prior treatment

• Subjects with levonorgestrel-releasing intrauterine system placed \>45 days prior to study enrollment.
• Subjects must not have more than one active malignancy at the time of enrollment (Subjects with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with safety or efficacy assessment of the study \[as determined by the treating physician or approved by the PI\] may be included).

Other illness

• Clinical suspicion of metastatic disease as assessed by the treating physician or confirmed metastatic disease based on imaging
• Subjects who are diagnosed with thyroid cancer, pancreatitis, or multiple endocrine neoplasia syndrome type 2
• History of medullary thyroid cancer
• Subjects with known current or history of hormonally- sensitive carcinoma (e.g., breast, melanoma)
• Prisoners or subjects who are involuntarily incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.

Lab values

• History of any other disease, metabolic dysfunction, clinical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician. This includes, but is not limited to, conditions such as New York Heart Association (NYHA) Class IV heart failure.

Other

• Subjects with grade 2 or 3 endometroid or any non-endometrioid histology (i.e., clear cell, carcinoma, serous)
• Subjects with abnormal cervical cytology
• Subjects who are confirmed to be pregnant or breastfeeding
• Subjects actively taking GLP-1RA for more than 14 days at time of consent.

• Adults ≥ 18 years old
• A pathological diagnosis with in the past 4 months consistent with grade 1 endometrioid endometrial adenocarcinoma or EIN
• For subjects with a diagnosis of endometrial intraepithelial neoplasia/grade 1 endometrioid endometrial adenocarcinoma prior to enrollment in the study, and with a diagnosis made outside this institution, the diagnostic material originating from outside the study site will undergo in-house pathology review before enrollment acceptance.
• ECOG Performance Status of 0 to 3
• For those with endometrial cancer, no extrauterine involvement or myometrial invasion by MRI (preferred) or transvaginal ultrasound
• BMI ≥ 30 kg/m2 and one of the following (per medical record or self-report):
  • Multiple medical co-morbidities (defined as American Society of Anesthesiologists \[ASA\] score ≥ 3) at physician discretion
  • Fertility desire
• Subject has had appropriate age-related breast examinations and imagining prior to study enrollment, as documented in the medical record or via investigator confirmation.
• Written informed consent obtained from the subject and the subject agrees to comply with all the study-related procedures.