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

NCT07781150 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: MELIA-IIT-001
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 6

Brief Summary

This is a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial designed to evaluate the efficacy and safety of mazdutide combined with a levonorgestrel-releasing intrauterine system (LNG-IUS) for fertility-sparing treatment in overweight or obese patients with atypical endometrial hyperplasia (AEH) or early-stage endometrioid endometrial cancer. Eligible participants will be randomized in a 1:1 ratio to receive LNG-IUS plus mazdutide or LNG-IUS plus matching placebo. The primary outcome is the complete response rate of endometrial lesions at 24 weeks after randomization.

Conditions

Obesity; Overweight; Atypical Endometrial Hyperplasia; Endometrial Carcinoma Stage I; Endometrioid Endometrial Cancer

Keywords

Mazdutide; Levonorgestrel-releasing intrauterine system; LNG-IUS; Atypical endometrial hyperplasia; Early endometrial cancer; Endometrioid endometrial cancer; Obesity

Outcome Measures

Primary Outcomes (1)

• Complete response rate of endometrial lesions at 24 week

  The proportion of participants who achieve complete response of endometrial lesions at the week 24 assessment. Complete response is defined as no residual AEH or endometrioid endometrial cancer on evaluable endometrial pathology obtained by hysteroscopic endometrial biopsy.

  At 24 weeks after randomization

Secondary Outcomes (22)

• Complete response rate at 12 weeks

  At 12 weeks after randomization

• Complete response rate at 36 weeks

  At 36 weeks after randomization

• Time to first complete response

  From randomization to first documented complete response, up to 36 weeks

• Pathological response status

  At 12, 24, and 36 weeks after randomization

• Fertility-sparing treatment failure and radical surgery

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

Study Arms (2)

LNG-IUS plus Mazdutide

EXPERIMENTAL

Participants will receive LNG-IUS placed in the uterine cavity and mazdutide by subcutaneous injection once weekly using a dose-escalation regimen.

Drug: Mazdutide(Dual GLP-1R/GCGR Agonist); Device: Levonorgestrel-releasing intrauterine system

LNG-IUS plus Placebo

PLACEBO COMPARATOR

Participants will receive LNG-IUS placed in the uterine cavity and matching placebo by subcutaneous injection once weekly using the same dose-escalation schedule as the mazdutide group.

Drug: Placebo; Device: Levonorgestrel-releasing intrauterine system

Interventions

Mazdutide(Dual GLP-1R/GCGR Agonist) DRUG

Mazdutide will be administered by subcutaneous injection once weekly. The starting dose is 2 mg once weekly for weeks 1-4, followed by 4 mg once weekly for weeks 5-8, and 6 mg once weekly from week 9 onward. If 6 mg is not tolerated, the dose may be reduced to 4 mg once weekly according to the protocol.

Also known as: IBI362

LNG-IUS plus Mazdutide

Placebo DRUG

Matching placebo will be administered by subcutaneous injection once weekly using the same injection route, frequency, injection volume, appearance, packaging, labeling, injection device, and dose-escalation procedure as mazdutide.

LNG-IUS plus Placebo

Levonorgestrel-releasing intrauterine system DEVICE

The levonorgestrel-releasing intrauterine system will be placed in the uterine cavity according to standard clinical practice and will be used as the background fertility-sparing progestin therapy in both treatment groups.

Also known as: LNG-IUS

LNG-IUS plus Mazdutide; LNG-IUS plus Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Eligible participants must be individuals assigned female at birth with an intact uterus and a diagnosis of atypical endometrial hyperplasia or early endometrioid endometrial cancer who meet all protocol-defined eligibility criteria. Gender identity is not used as an independent eligibility criterion.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tongji Hospital: lead
• Innovent Biologics, Inc.: collaborator

Study Sites (6)

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Location

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Location

The Second Hospital of Jilin University

Changchun, Jilin, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Location

Shanghai Tenth People's Hospital

Shanghai, China

Location

Tianjin Medical University General Hospital

Tianjin, China

Location

MeSH Terms

Conditions

Obesity; Overweight; Endometrial Hyperplasia; Endometrial Neoplasms

Interventions

mazdutide

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms

Study Officials

• Gang Chen, Principal Investigator

  Tongji Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gang Chen, Principal Investigator

CONTACT

+8618838289119; tjchengang@hust.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Mazdutide and matching placebo will be identical or matched in appearance, packaging, labeling, injection device, injection volume, route, dosing frequency, and dose-escalation procedure. Participants, investigators, care providers, and outcome assessors will remain blinded to treatment allocation. Pathology assessment will be performed without knowledge of randomized treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Co-Principal Investigator

Model Details: Participants will be randomized in a 1:1 ratio to receive LNG-IUS plus mazdutide or LNG-IUS plus matching placebo. Randomization will be implemented through an interactive web response system, with stratification by study center, baseline disease type, and BMI category.

Study Record Dates

• First Submitted: August 18, 2026
• First Posted: August 24, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2031
• Last Updated: August 24, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)