Recruiting

Phase 2

MK-5684 vs. Standard TreatmentsA Study of MK-5684 in People With Certain Solid Tumors (MK-5684-015/OMAHA-015)

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT06979596

Conditions

Malignant Neoplasm

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Opevesostat

Fludrocortisone/ Fludrocortisone acetate

Dexamethasone/Dexamethasone acetate

Rescue Medications

Fulvestrant

Study Details

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

Study ID

NCT06979596

Start date

Aug 11, 2025

Status verified date

Aug, 2026

Completion date

Nov 4, 2027

Anticipated

Primary completion date

Nov 4, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

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.

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

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.
Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
Has known active central nervous system metastases and/or carcinomatous meningitis.
Has a history of stem cell/solid organ transplant.
Has not adequately recovered from major surgery or has ongoing surgical complications.

Study Design

Enrollment

250 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: MK-5684 and Daily Corticosteroids

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.

experimental: Fulvestrant or Exemestane

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.

no intervention: Observation (No Treatment)

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

experimental: Treatment of Physician's Choice

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.

Interventions

Opevesostat