MELIA

Not yet recruitingPhase 2

Mazdutide Plus LNG-IUS for Fertility-Sparing Treatment of AEH or Early Endometrial Cancer

Mazdutide Plus Levonorgestrel-Releasing Intrauterine System for Fertility-Sparing Treatment in Overweight or Obese Patients With Atypical Endometrial Hyperplasia or Early Endometrioid Endometrial Cancer

Lead sponsor

Tongji Hospital

Asset

Mazdutide

Subcutaneous · GLP-1 / glucagon dual

Listed sites

Recruiting sites

Estimated enrollment

128

Study population

Obesity / overweight, Oncology

Eligibility highlights

•BMI ≥28•Female

Primary endpoint

•Complete response rate of endometrial lesions

Registered trial locations

Locations reported to ClinicalTrials.gov for this trial snapshot. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT07781150

Org study IDMELIA-IIT-001

Timeline

Milestones

Study first posted2026-08-24actual

Last update posted2026-08-24actual

Study start2026-11-01estimated

Primary completion2029-06-30estimated

Study completion2031-06-30estimated

Assets

Investigational agents

Mazdutide

Who this study enrolls

Obesity / overweightOncology

Who can enroll

Minimum age18 Years

Maximum age45 Years

SexFemale

Healthy volunteersNot accepted

Inclusion criteria

•Female participants aged 18 to 45 years.

•Participants have a clear desire to preserve fertility, fully understand that fertility-sparing treatment is not the standard radical treatment for endometrial cancer, are willing to accept the potential risks of disease progression or recurrence associated with delayed radical surgery, and are able to comply with close follow-up as required by the protocol.

•Histologically confirmed disease meeting one of the following criteria: atypical endometrial hyperplasia; or FIGO grade 1 endometrioid endometrial cancer meeting FIGO 2023 stage IA1, with disease confined to the endometrium or an endometrial polyp and no myometrial invasion.

•Imaging confirms disease confined to the endometrium, with no evidence of myometrial invasion, adnexal involvement, extrauterine disease, or distant metastasis.

•Estrogen receptor-positive disease.

•Molecular pathology requirements are fulfilled for participants with endometrial cancer, including exclusion of the p53-abnormal molecular subtype. For participants with POLE-ultramutated or mismatch repair-deficient tumors, suitability for fertility-sparing treatment should be determined based on age, family history, genetic findings, and multidisciplinary assessment. Genetic counseling, germline testing, or additional molecular testing may be performed when clinically indicated.

•No contraindication to progestin therapy.

•Uterine cavity suitable for LNG-IUS placement.

•Completed baseline fertility assessment; after complete response, a specific pregnancy plan should be developed after evaluation by reproductive specialists.

•BMI ≥28 kg/m2, or BMI ≥24 kg/m2 with at least one weight-related comorbidity, such as hyperglycemia, hypertension, dyslipidemia, fatty liver disease, or obstructive sleep apnea.

•No contraindication to mazdutide.

•No contraindication to LNG-IUS.

•Able to understand and sign informed consent and willing to comply with all study treatments, assessments, and follow-up procedures.

Exclusion criteria

•Pathological diagnosis not consistent with atypical endometrial hyperplasia or eligible early endometrioid endometrial cancer; endometrioid carcinoma grade 2 or higher; or p53-abnormal molecular subtype.

•Imaging or pathological evidence of myometrial invasion, ovarian malignancy, extrauterine disease, or distant metastasis.

•Prior fertility-sparing drug therapy or intrauterine progestin therapy for atypical endometrial hyperplasia or endometrial cancer.

•Use of hormonal therapy or GLP-1 receptor agonists within 6 months before enrollment.

•Pregnancy or breastfeeding at enrollment.

•Request for hysterectomy or treatment other than conservative medical therapy.

•Active pelvic inflammatory disease, recurrent pelvic inflammatory disease, or lower genital tract infection.

•Cervical dysplasia or congenital or acquired uterine abnormalities, including fibroids that distort the uterine cavity.

•Uterine cavity too large for adequate LNG-IUS coverage or history of LNG-IUS expulsion.

•Known hypersensitivity to mazdutide, any of its excipients, or LNG-IUS materials.

•History of malignancy at another site.

•Uncontrolled clinically significant comorbidities or medical history that may increase study risk or interfere with study evaluation, including cardiovascular, cerebrovascular, thromboembolic, hepatic, renal, coagulation, endocrine, psychiatric, pancreatic, biliary, or severe gastrointestinal disorders.

•Diabetes diagnosed by oral glucose tolerance test.

•Secondary obesity or endocrine disorders that may affect body weight or metabolic assessment.

•Contraindications or major risk factors related to GLP-1 receptor agonist therapy, including pancreatitis, clinically significant gallbladder disease, severe gastrointestinal motility disorder, medullary thyroid carcinoma, or multiple endocrine neoplasia type 2.

•Participation in another interventional clinical trial.

•Any condition that, in the investigator's opinion, may increase risk during study treatment, interfere with safety assessment, or affect interpretation of study results.

Endpoints (23)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Weight & body composition

Cardiometabolic biomarkers

Glycemic / diabetes

Other clinical outcomes

MASH / liver

Other (unclassified)

Weight & body composition

6 endpoints

Secondary/protocol endpoint

Change in body weight

Time frame:Baseline, 12 weeks, 24 weeks, and 36 weeks after randomization

change from baseline, improvement

Secondary/protocol endpoint

Percentage change in body weight

Time frame:Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

percent change from baseline, improvement

Secondary/protocol endpoint

Proportion of participants with at least 5% body weight reduction

Time frame:At 12, 24, and 36 weeks after randomization

threshold achievement, improvement

Secondary/protocol endpoint

Proportion of participants with at least 10% body weight reduction

Time frame:At 12, 24, and 36 weeks after randomization

threshold achievement, improvement

Secondary/protocol endpoint

Change in body mass index

Time frame:Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

change from baseline, improvement

Secondary/protocol endpoint

Change in waist circumference

Time frame:Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

change from baseline, improvement

Glycemic / diabetes

4 endpoints

Secondary/protocol endpoint

Change in fasting plasma glucose

Time frame:Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

change from baseline, improvement

Secondary/protocol endpoint

Change in HbA1c

Time frame:Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

change from baseline, improvement

Secondary/protocol endpoint

Change in fasting insulin

Time frame:Baseline, 24 weeks, and at early discontinuation of study treatment if applicable

change from baseline, improvement

Secondary/protocol endpoint

Change in HOMA-IR

Time frame:Baseline, 24 weeks, and at early discontinuation of study treatment if applicable

change from baseline, improvement

MASH / liver

2 endpoints

Secondary/protocol endpoint

Change in alanine aminotransferase

Time frame:Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

change from baseline, improvement

Secondary/protocol endpoint

Change in aspartate aminotransferase

Time frame:Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

change from baseline, improvement

Cardiometabolic biomarkers

5 endpoints

Secondary/protocol endpoint

Change in total cholesterol

Time frame:Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

change from baseline, improvement

Secondary/protocol endpoint

Change in triglycerides

Time frame:Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

change from baseline, improvement

Secondary/protocol endpoint

Change in LDL cholesterol

Time frame:Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

change from baseline, improvement

Secondary/protocol endpoint

Change in HDL cholesterol

Time frame:Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

change from baseline, improvement

Secondary/protocol endpoint

Change in serum uric acid

Time frame:Baseline, 12 weeks, 24 weeks, 36 weeks, and at early discontinuation of study treatment if applicable

change from baseline, improvement

Other clinical outcomes

4 endpoints

Primary/protocol endpoint

Complete response rate of endometrial lesions at 24 week

Time frame:At 24 weeks after randomization

descriptive

Secondary/protocol endpoint

Complete response rate at 12 weeks

Time frame:At 12 weeks after randomization

descriptive

Secondary/protocol endpoint

Complete response rate at 36 weeks

Time frame:At 36 weeks after randomization

descriptive

Secondary/protocol endpoint

Fertility-sparing treatment failure and radical surgery

Time frame:From randomization through the end of study follow-up, up to 2 years after complete response

descriptive

Other (unclassified)

2 endpoints

Secondary/protocol endpoint/low confidence

Time to first complete response

Time frame:From randomization to first documented complete response, up to 36 weeks

time to event, event

Secondary/protocol endpoint/low confidence

Pathological response status

Time frame:At 12, 24, and 36 weeks after randomization

categorical status, descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateNovember 5, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the November 5, 2026 snapshot.