The primary objective of the trial is to evaluate the effect of maridebart cafraglutide on the pharmacokinetics (PK) of a combined oral contraceptive (COC) in postmenopausal female participants living with overweight or obesity.

Inclusion Criteria

1. Participants must be postmenopausal females 45 to 65 years of age. Postmenopausal status must be confirmed based on the protocol-defined criteria.
2. Body mass index must be ≥ 25.0 and ≤ 38.0 kg/m^2.
3. Body weight must be stable, with less than 5 kg self-reported change in the 3 months before screening.
4. Participants must not have changed their diet or started a nutritional lifestyle modification program within 3 months before screening.
5. Other inclusion criteria may apply.

Exclusion Criteria

1. History or evidence of any clinically significant medical condition, abnormal physical exam, ECG, vital sign, or laboratory finding that could increase risk or interfere with study participation.
2. History of diabetes, active diabetes, or hemoglobin A1c 6.5% or higher.
3. Endocrine disorders that can cause obesity, such as Cushing's syndrome.
4. History of acute or chronic pancreatitis within 1 year before check-in, pancreatic enzyme elevations greater than 2 times the upper limit of normal, or fasting triglycerides greater than 300 mg/dL.
5. Bleeding or clotting disorders, abnormal coagulation tests, or a history of venous or arterial blood clots or conditions that increase clot risk.
6. LDL cholesterol greater than 159 mg/dL.
7. Migraine with aura, normal pressure hydrocephalus, or ischemic optic neuropathy.
8. Malignancy within the past 5 years, except nonmelanoma skin cancer.
9. Unexplained postmenopausal vaginal bleeding, untreated endometrial disease, or other gynecologic conditions that could worsen with estrogen/progestin therapy.
10. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2, or uncontrolled thyroid disease.
11. Gastroparesis, inability to swallow oral medication, clinically important gastrointestinal disease, malabsorption, uncontrolled inflammatory bowel disease, certain gastrointestinal surgeries, or recent bariatric surgery.
12. Clinically significant cardiovascular disease, clinically significant arrhythmia, long QT syndrome, QTcF greater than 470 msec, second- or third-degree atrioventricular block, or clinically important abnormal pulse rate or systolic blood pressure > 150 mmHg or < 90 mmHg, diastolic blood pressure > 95 mmHg or < 50 mmHg.
13. Allergy, hypersensitivity, intolerance, or contraindication to maridebart cafraglutide, ethinyl estradiol, or orgestimate.
14. Reduced kidney function with estimated glomerular filtration rate 60 mL/min/1.73 m^2 or lower, ALT or AST greater than 2 times the upper limit of normal, or a history of acute or chronic liver disease, hepatic adenoma, or hepatic carcinoma.
15. Hemoglobin or hematocrit below the lower limit of normal.
16. Positive HIV test, or positive hepatitis B surface antigen or hepatitis C antibody at screening.
17. Lifetime history of suicide attempt, non-suicidal self-injury within 5 years, or unstable major depressive disorder or other severe psychiatric disorder within 2 years.
18. Positive pregnancy test at screening or check-in.
19. Recent use of medications that could affect study participation, including most prescription or over-the-counter medications, systemic hormone replacement therapy, certain contraceptive hormones, CYP enzyme inducers or inhibitors, GLP-1 receptor or GIP receptor agents, and nonpermitted herbal products, vitamins, or supplements.
20. Recent participation in another investigational study, prior participation in this study, or prior exposure to maridebart cafraglutide.
21. Tobacco or nicotine use within 3 months before check-in, positive cotinine test, history of alcoholism or drug abuse, positive alcohol or illicit drug testing, recent illicit drug use, or unwillingness to avoid illicit drugs or cannabinoids during the study.
22. Recent blood, plasma, or platelet donation.
23. Other exclusion criteria may apply.

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Data sharing requests relating to this trial will be considered beginning 18 months after the trial has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this trial.

Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen trial/trials in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.