A Study of MK-5684 in People With Certain Solid Tumors (MK-5684-015/OMAHA-015)

NCT06979596 | Recruiting Phase 2 FDA Drug

• 5 other identifiers: 5684-0152024-519563-18-00U1111-1315-5430MK-5684-015OMAHA-015
• Study Type: interventional
• Target: 250
• Locations: 13 countries
• Sites: 55

Brief Summary

Researchers want to learn if MK-5684 (the study medicine) can treat breast cancer, ovarian cancer, and endometrial cancer. MK-5684, the study medicine, is designed to treat cancer by blocking the body from making steroid hormones. Researchers will compare MK-5684 to the standard treatments for each cancer type in this study. The goal of this study is to learn if people who receive MK-5684 live longer without the cancer growing or spreading compared to people who receive a standard treatment.

Conditions

Malignant Neoplasm

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) - All Cohorts

  For all cohorts, PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review (BICR) will be presented.

  Up to approximately 2 years

Secondary Outcomes (6)

• Overall Survival (OS) - All Cohorts

  Up to approximately 2 years

• Clinical Benefit Rate (CBR) - Cohort A

  Up to approximately 2 years

• Objective Response Rate (ORR) - All Cohorts

  Up to approximately 2 years

• Duration of Response (DOR) - All Cohorts

  Up to approximately 2 years

• Number of Participants who Discontinue Study Intervention Due to an Adverse Event (AE) - All Cohorts

  Up to approximately 8 months

Study Arms (4)

MK-5684 and Daily Corticosteroids

EXPERIMENTAL

Participants with breast cancer, ovarian cancer, or endometrial cancer will receive 5 mg of MK-5684 orally twice daily. Participants will also receive fludrocortisone/fludrocortisone acetate starting at 0.1 mg orally, and dexamethasone/dexamethasone acetate starting at 1 mg orally; both will be adjusted individually during the study. Participants will receive treatment until one of the conditions for discontinuation of study intervention is met.

Drug: Opevesostat; Drug: Fludrocortisone/ Fludrocortisone acetate; Drug: Dexamethasone/Dexamethasone acetate; Drug: Rescue Medications

Fulvestrant or Exemestane

EXPERIMENTAL

Participants with breast cancer receive endocrine therapy of the physician's choice: either 500 mg of fulvestrant on Day 1 and Day 15 of Cycle 1 and Day 1 of every cycle thereafter (cycles are 28 days in length) or 25 mg of exemestane once daily (QD). Participants will receive treatment until one of the conditions for discontinuation of study intervention is met.

Drug: Fulvestrant; Drug: Exemestane

Observation (No Treatment)

NO INTERVENTION

Participants with ovarian cancer will be observed but will receive no treatment for the duration of the study.

Treatment of Physician's Choice

EXPERIMENTAL

Participants with endometrial cancer will receive the physician's choice of either 80 mg megestrol acetate/medroxyprogesterone acetate twice daily, or alternating between 80 mg megestrol acetate twice daily for three weeks and 20 mg tamoxifen twice daily for three weeks, or 2.5 mg letrozole once daily. Participants will receive treatment until one of the conditions for discontinuation of study intervention is met.

Drug: Megestrol acetate/Medroxyprogesterone acetate; Drug: Tamoxifen; Drug: Letrozole

Interventions

Opevesostat DRUG

Tablet for oral administration.

Also known as: MK-5684

MK-5684 and Daily Corticosteroids

Fludrocortisone/ Fludrocortisone acetate DRUG

Tablet for oral administration.

MK-5684 and Daily Corticosteroids

Dexamethasone/Dexamethasone acetate DRUG

Tablet for oral administration.

MK-5684 and Daily Corticosteroids

Rescue Medications DRUG

Hydrocortisone or hydrocortisone/hydrocortisone acetate administered via intramuscular injection as rescue medication.

MK-5684 and Daily Corticosteroids

Fulvestrant DRUG

Administered via intramuscular injection.

Fulvestrant or Exemestane

Exemestane DRUG

Tablet for oral administration.

Fulvestrant or Exemestane

Megestrol acetate/Medroxyprogesterone acetate DRUG

Tablet for oral administration.

Treatment of Physician's Choice

Tamoxifen DRUG

Tablet for oral administration.

Treatment of Physician's Choice

Letrozole DRUG

Tablet for oral administration.

Treatment of Physician's Choice

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohort A:
• Has a diagnosis of hormone receptor positive/Human Epidermal Growth Factor Receptor 2 negative (HR+/HER2-) invasive breast carcinoma that is either locally advanced disease not amenable to resection with curative intent (herein called unresectable) or metastatic disease not treatable with curative intent.
• Has experienced disease progression on or after at least 1 prior endocrine-based therapy in the metastatic setting and received either, 1 line of an approved protocol-specified combination endocrine-based therapy, or 2 or more lines of protocol-specified endocrine-based therapy in the metastatic setting
• Cohort B:
• Has histologically confirmed high-grade epithelial (including high-grade serous or predominantly serous, high-grade endometrioid, malignant mixed Müllerian tumors \[carcinosarcoma\], or clear cell) ovarian, fallopian tube, or primary peritoneal carcinoma.
• Has received between 4 to 8 cycles of platinum-based doublet chemotherapy in third-line (3L) setting for ovarian cancer.
• Cohort C:
• Histologically confirmed diagnosis of primary advanced or recurrent low-grade endometrioid carcinoma (eg, Federation of Gynecology and Obstetrics \[FIGO\] Grade 1/2, or well/moderately differentiated).
• Treatment naïve or has received up to 1 prior line of platinum-based therapy in either the advanced/metastatic OR adjuvant/neoadjuvant setting.
• All Cohorts :
• Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline.
• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy.
• Participants who are Hepatitis B surface antigen positive are eligible if they have received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load.
• Participants with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable.

You may not qualify if:

• Cohort A:
• Breast cancer amenable to treatment with curative intent.
• Has advanced/metastatic, symptomatic visceral spread at risk of rapidly evolving into life-threatening complications, such as lymphangitic lung metastases, radiographic evidence of intratumoral cavitation or invasion/infiltration of a major blood vessel, bone marrow replacement, carcinomatous meningitis, significant symptomatic liver metastases, symptomatic pericardial effusion, symptomatic peritoneal carcinomatosis, or the need to achieve rapid symptom control.
• Cohort B:
• Has nonepithelial cancers (germ cell tumors and sex cord-stromal tumors), borderline tumors (low malignant potential), mucinous, seromucinous that is predominantly mucinous, malignant Brenner's tumor, low-grade serous, low-grade endometrioid, and undifferentiated carcinoma.
• Has platinum-resistant ovarian cancer (defined as disease that has progressed per radiographic imaging within 180 days after the last dose of first-line \[1L\] platinum-based therapy) or platinum-refractory ovarian cancer (defined as disease that has progressed per radiographic imaging while receiving or within 28 days of the last dose of 1L platinum based therapy).
• Is a candidate for curative-intent surgery or curative-intent radiotherapy for ovarian cancer.
• Cohort C:
• Has high-grade (FIGO Grade 3 or poorly differentiated) endometrioid carcinoma and nonendometrioid histologies of any type (including serous, clear cell, mixed, carcinosarcoma), and neuroendocrine tumors are not eligible. Uterine mesenchymal tumors such as an endometrial stromal sarcoma, leiomyosarcoma, or other types of pure sarcomas, and adenosarcomas are not eligible.
• Is a candidate for curative-intent surgery or curative-intent radiotherapy.
• All Cohorts:
• Has confirmed or suspected adrenal metastases.
• Has known difficulty in tolerating oral medications, unable to swallow orally administered medication, or conditions which would impair absorption of oral medications.
• Has any prior history or current condition of adrenal insufficiency.
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (55)

Alaska Womens Cancer Care ( Site 0037)

Anchorage, Alaska, 99508, United States

RECRUITING

Mount Sinai Cancer Center ( Site 0009)

Miami Beach, Florida, 33140, United States

RECRUITING

TRIALS 365 ( Site 0022)

Shreveport, Louisiana, 71103, United States

RECRUITING

Mary Lanning Healthcare ( Site 0019)

Hastings, Nebraska, 68901, United States

RECRUITING

John Theurer Cancer Center at Hackensack University Medical Center ( Site 0021)

Hackensack, New Jersey, 07601, United States

RECRUITING

Memorial Sloan Kettering Cancer Center ( Site 0002)

New York, New York, 10065, United States

RECRUITING

The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C ( Site 0008)

Columbus, Ohio, 43210, United States

RECRUITING

Baylor College of Medicine Medical Center ( Site 0004)

Houston, Texas, 77030, United States

RECRUITING

Mays Cancer Center ( Site 0039)

San Antonio, Texas, 78229, United States

RECRUITING

Hospital Aleman ( Site 0301)

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1118AAT, Argentina

RECRUITING

Centro Medico Dr. Doreski - Fundación Respirar ( Site 0302)

Buenos Aires, Buenos Aires F.D., C1118AAT, Argentina

RECRUITING

Instituto Alexander Fleming ( Site 0303)

Buenos Aires, Buenos Aires F.D., C1426ANZ, Argentina

RECRUITING

Hospital Santa Rita de Cassia ( Site 3104)

Vitória, Espírito Santo, 29043-260, Brazil

RECRUITING

Obras Sociais Irma Dulce ( Site 3112)

Salvador, Estado de Bahia, 41680-430, Brazil

RECRUITING

Hospital Felicio Rocho ( Site 3105)

Belo Horizonte, Minas Gerais, 30110-934, Brazil

RECRUITING

Hospital de Cancer de Pernambuco ( Site 3103)

Recife, Pernambuco, 50040-000, Brazil

RECRUITING

Liga Norte Riograndense Contra o Cancer ( Site 3108)

Natal, Rio Grande do Norte, 59062-000, Brazil

RECRUITING

Instituto Nacional de Câncer - INCA ( Site 3107)

Rio de Janeiro, 20230-130, Brazil

RECRUITING

Princess Margaret Cancer Centre ( Site 0202)

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

FALP ( Site 3300)

Santiago, Region M. de Santiago, 7500921, Chile

RECRUITING

Pontificia Universidad Catolica de Chile ( Site 3307)

Santiago, Region M. de Santiago, 8330032, Chile

RECRUITING

Bradfordhill ( Site 3301)

Santiago, Region M. de Santiago, 8420383, Chile

RECRUITING

ONCOCENTRO APYS ( Site 3302)

Viña del Mar, Valparaiso, 2520598, Chile

RECRUITING

Sarawak General Hospital ( Site 0602)

Kuching, Sarawak, 93586, Malaysia

RECRUITING

Pantai Hospital Kuala Lumpur ( Site 0603)

Kuala Lumpur, 59100, Malaysia

RECRUITING

University Malaya Medical Centre ( Site 0601)

Kuala Lumpur, 59100, Malaysia

RECRUITING

Instituto Regional de Enfermedades Neoplasicas del Centro (IREN CENTRO) ( Site 3405)

Concepción, Departamento de Junín, 12125, Peru

RECRUITING

Clínica San Antonio ( Site 3404)

Trujillo, La Libertad, 13008, Peru

RECRUITING

IPOR Instituto Peruano de Oncología & Radioterapia ( Site 3400)

Lima, 15036, Peru

RECRUITING

Instituto Nacional de Enfermedades Neoplásicas ( Site 3401)

Lima, 15038, Peru

RECRUITING

National Cancer Centre Singapore ( Site 0800)

Singapore, Central Singapore, 168583, Singapore

RECRUITING

Institut Català d'Oncologia - L'Hospitalet-Medical Oncology ( Site 2000)

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

RECRUITING

CHUAC-Complejo Hospitalario Universitario A Coruña ( Site 2003)

A Coruña, La Coruna, 15006, Spain

RECRUITING

Clinica Universitaria Navarra - Madrid ( Site 2004)

Madrid, Madrid, Comunidad de, 28027, Spain

RECRUITING

Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 2002)

Madrid, Madrid, Comunidad de, 28034, Spain

RECRUITING

HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID-ONCOLOGIA MEDICA ( Site 2001)

Madrid, 28223, Spain

RECRUITING

Taichung Veterans General Hospital ( Site 1004)

Taichung, 407, Taiwan

RECRUITING

National Cheng Kung University Hospital ( Site 1003)

Tainan, 704, Taiwan

RECRUITING

Mackay Memorial Hospital ( Site 1002)

Taipei, 10449, Taiwan

RECRUITING

Chulalongkorn Hospital ( Site 1114)

Bangkok, Bangkok, 10330, Thailand

RECRUITING

Faculty of Medicine Siriraj Hospital ( Site 1111)

Bangkok, Bangkok, 10700, Thailand

RECRUITING

Songklanagarind Hospital ( Site 1113)

Songkhla, 90110, Thailand

RECRUITING

Baskent Universitesi Adana Dr. Turgut Noyan Uygulama ve Arastirma Merkezi ( Site 2201)

Adana, 01240, Turkey (Türkiye)

RECRUITING

Hacettepe Universitesi ( Site 2200)

Ankara, 06230, Turkey (Türkiye)

RECRUITING

Trakya Üniversitesi Eğitim Araştırma Hastanesi ( Site 2204)

Edirne, 22030, Turkey (Türkiye)

RECRUITING

Istanbul Universitesi Cerrahpasa ( Site 2203)

Istanbul, 34098, Turkey (Türkiye)

RECRUITING

Koc University, School of Medicine ( Site 2202)

Istanbul, 34450, Turkey (Türkiye)

RECRUITING

University Hospitals Sussex NHS Foundation Trust ( Site 2301)

East Sussex, Brighton And Hove, BN2 1ES, United Kingdom

RECRUITING

The Royal Cornwall Hospital ( Site 2306)

Truro, Cornwall, TR1 3LJ, United Kingdom

RECRUITING

St Bartholomew's Hospital ( Site 2302)

London, London, City of, EC1A 7BE, United Kingdom

RECRUITING

University College Hospital London ( Site 2303)

London, London, City of, NW1 2PG, United Kingdom

RECRUITING

Guy's & St Thomas' NHS Foundation Trust ( Site 2309)

London, London, City of, SE1 9RT, United Kingdom

RECRUITING

Western General Hospital ( Site 2307)

Edinburgh, Midlothian, EH4 2XU, United Kingdom

RECRUITING

Queen Elizabeth Hospital ( Site 2305)

Birmingham, B15 2GW, United Kingdom

RECRUITING

The Christie NHS Foundation Trust ( Site 2300)

Manchester, M20 4BX, United Kingdom

RECRUITING

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Neoplasms

Interventions

fludrocortisone acetate; dexamethasone acetate; Fulvestrant; exemestane; Megestrol Acetate; Medroxyprogesterone Acetate; Tamoxifen; Letrozole

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Megestrol; Pregnadienes; Pregnanes; Medroxyprogesterone; Hydroxyprogesterones; Progesterone; Pregnenediones; Pregnenes; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2025
• First Posted: May 20, 2025
• Study Start: August 11, 2025
• Primary Completion (Estimated): November 4, 2027
• Study Completion (Estimated): November 4, 2027
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

AR (3); PE (4); BR (6); GB (8); TH (3); ES (5); MY (3); CA (1); SG (1); TU (5); US (9); CL (4); TW (3)