A Clinical Trial of MK-6255 to Treat Endometrial and Ovarian Cancer (MK-6255-001)

• MK-6255 (Biological): During initial dose escalation, participants will receive MK-6255 one weekly (QW). During Dose Interval Extension, participants will receive target doses every 3 weeks (Q3W).
• CD8 PET Tracer (Other), also known as GEH200520, GEH200521 (18F): Participants may receive an optional CD8 PET tracer for exploratory imaging assessments.
• Acetaminophen (Drug): Participants will receive acetaminophen (or similar antipyretic) as premedication.
• Diphenhydramine (Drug): Participants will receive diphenhydramine (or similar antihistamine) as premedication.
• Dexamethasone (Drug): Participants will receive dexamethasone as premedication.
• Tocilizumab (Biological): Participants will receive this rescue medication at the investigator's discretion for treatment of cytokine release syndrome (CRS) after MK-6255 administration.
• Tocilizumab biosimilar (Biological), also known as Avtozma®, Tyenne®: Participants will receive this rescue medication at the investigator's discretion for treatment of cytokine release syndrome (CRS) after MK-6255 administration.
• Siltuximab (Biological): Participants will receive this rescue medication at the investigator's discretion for treatment of cytokine release syndrome (CRS) after MK-6255 administration.

Primary outcomes

• Number of Participants Who Experience a Dose-limiting Toxicity (DLT) as Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 6.0 [Up to 21 days at each dose level]: A DLT is defined as any drug-related AE observed during the DLT evaluation period that meet criteria specified in the protocol. DLTs will be evaluated until 21 days after the first fixed dose during fixed-dose escalation and until 21 days after the first target dose during step-up dose escalation and dose interval extension.
• Number of participants who experience one or more adverse events (AEs) [Up to approximately 56 months]: An AE is 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. The number of participants that experience AEs will be reported.
• Number of participants who discontinue study intervention due to an adverse event (AE) [Up to approximately 56 months]: An AE is 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. The number of participants that discontinue study intervention due to an AE will be reported.

Secondary outcomes

• Area Under the Serum Concentration-Time Curve (AUC) of MK-6255 [At designated timepoints (up to approximately 2 weeks postdose)]: AUC is defined as the measure of overall drug exposure over time after administration. Blood samples will be collected to determine the AUC of MK-6255.
• Minimum Serum Concentration (Cmin) of MK-6255 [At designated timepoints (up to approximately 2 weeks postdose)]: Cmin is defined as the lowest observed concentration of a drug after administration. Blood samples will be collected to determine the Cmin of MK-6255.
• Maximum Serum Concentration (Cmax) of MK-6255 [At designated timepoints (up to approximately 2 weeks postdose)]: Cmax is defined as the highest observed concentration of a drug after administration. Blood samples will be collected to determine the Cmax of MK-6255.
• Time to Maximum Serum Concentration (Tmax) of MK-6255 [At designated timepoints (up to approximately 2 weeks postdose)]: Tmax is defined as the time at which the maximum observed concentration of a drug occurs after administration. Blood samples will be collected to determine the Tmax of MK-6255.

Sex: Female, ages: 18 Years to any

Inclusion Criteria:

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

* Has one of the following diagnoses:

  * Recurrent, pathologically documented epithelial OC, primary peritoneal cancer, or fallopian tube cancer that is either (1) platinum resistant or (2) platinum sensitive, with progression during prior treatment with poly-adenosine diphosphate (ADP) ribose polymerase inhibitor (PARPi)
  * Histologically confirmed well, moderately, or poorly differentiated (ie, Grade 1 to Grade 3) serous or endometrioid EC that has progressed after at least 1 line of platinum-based therapy in any setting
* Has received all protocol-required and available standard of care (SOC) therapies, unless ineligible for or intolerant to the therapies
* Has provided archival tumor tissue or a recently obtained biopsy before treatment start
* If living with human immunodeficiency virus (HIV), has well-controlled HIV on antiretroviral therapy (ART)
* If hepatitis B surface antigen (HBsAg)-positive, has undetectable hepatitis B virus (HBV) viral load and has received HBV antiviral - therapy for at least 4 weeks
* If history of hepatitis C virus (HCV) infection, has undetectable HCV viral load
* Has adequate organ function

Exclusion Criteria:

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

* Has a diagnosis of any 1 of the following: Primary platinum-refractory OC; neuroendocrine tumors or endometrial sarcoma, including stromal sarcoma, leiomyosarcoma, adenosarcoma, or other types of pure sarcomas; carcinosarcoma; EC that is amenable to curative-intent surgery or curative-intent radiotherapy; or EC that requires recurrent drainage of effusions
* Has a history of serious cardiovascular and cerebrovascular diseases
* Has a history or presence of clinically relevant central nervous system (CNS) diseases
* Has received prior systemic anticancer therapy within 4 weeks or 5 half-lives (whichever is shorter) before start of study intervention
* Has received prior radiotherapy within 2 weeks of start of study intervention
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has known active CNS metastases and/or carcinomatous meningitis
* Has active autoimmune disease that has required systemic treatment in the past 2 years
* Is living with HIV and has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* 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