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

Merck Sharp & Dohme (MSD)

Status and phase: Enrolling; Phase 2

Conditions: Malignant Neoplasm

Treatments: Drug: Megestrol acetate/Medroxyprogesterone acetate; Drug: Exemestane; Drug: Tamoxifen; Drug: Opevesostat; Drug: Fulvestrant; Drug: Rescue Medications; Drug: Fludrocortisone/ Fludrocortisone acetate; Drug: Dexamethasone/Dexamethasone acetate; Drug: Letrozole

Study type: Interventional

Funder types: Industry

Identifiers

NCT06979596

OMAHA-015 (Other Identifier)

2024-519563-18-00 (Registry Identifier)

U1111-1315-5430 (Other Identifier)

5684-015

MK-5684-015 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 250 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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250 participants in 4 patient groups

MK-5684 and Supportive Adrenal Therapy (SAT)

Experimental group

Description:

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.

Treatment:

Drug: Dexamethasone/Dexamethasone acetate

Drug: Rescue Medications

Drug: Fludrocortisone/ Fludrocortisone acetate

Drug: Opevesostat

Fulvestrant or Exemestane

Experimental group

Description:

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.

Treatment:

Drug: Fulvestrant

Drug: Exemestane

Observation (No Treatment)

No Intervention group

Description:

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

Treatment of Physician's Choice

Experimental group

Description:

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.

Treatment:

Drug: Letrozole

Drug: Tamoxifen

Drug: Megestrol acetate/Medroxyprogesterone acetate