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

• Opevesostat (Drug), also known as MK-5684: Tablet for oral administration.
• Fludrocortisone/ Fludrocortisone acetate (Drug): Tablet for oral administration.
• Dexamethasone/Dexamethasone acetate (Drug): Tablet for oral administration.
• Rescue Medications (Drug): Hydrocortisone or hydrocortisone/hydrocortisone acetate administered via intramuscular injection as rescue medication.
• Fulvestrant (Drug): Administered via intramuscular injection.
• Exemestane (Drug): Tablet for oral administration.
• Megestrol acetate/Medroxyprogesterone acetate (Drug): Tablet for oral administration.
• Tamoxifen (Drug): Tablet for oral administration.
• Letrozole (Drug): Tablet for oral administration.

Primary outcomes

• Progression-Free Survival (PFS) - All Cohorts [Up to approximately 2 years]: 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.

Secondary outcomes

• Overall Survival (OS) - All Cohorts [Up to approximately 2 years]: For all cohorts, OS is defined the time from randomization to death due to any cause.
• Clinical Benefit Rate (CBR) - Cohort A [Up to approximately 2 years]: For cohort A (participants with breast cancer), CBR is defined as the percentage of participants who have complete response (CR): disappearance of all target lesions; partial response (PR): At least a 30% decrease in the sum of diameters of target lesions; or stable disease (SD): Neither sufficient decrease to qualify for PR nor sufficient increase to qualify for progressive disease (PD), with reference to the smallest sum diameters while on study) for ≥24 weeks per RECIST 1.1 as assessed by BICR.
• Objective Response Rate (ORR) - All Cohorts [Up to approximately 2 years]: For all cohorts, ORR is defined as the percentage of participants who have achieved confirmed Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by BICR.
• Duration of Response (DOR) - All Cohorts [Up to approximately 2 years]: For all cohorts, for participants who demonstrate CR or PR, DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.
• Number of Participants who Discontinue Study Intervention Due to an Adverse Event (AE) - All Cohorts [Up to approximately 8 months]: An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
• Number of Participants who Experience One or More Adverse Events (AEs) - All Cohorts [Up to approximately 11 months]: An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

Sex: All, ages: 18 Years to any

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.

• Medical Director, Study director, Merck Sharp & Dohme LLC