Ovarian Neoplasms, Endometrial Neoplasms
Conditions
Brief summary
Researchers are looking for new ways to treat advanced and recurrent endometrial cancer (EC) and ovarian cancer (OC). Advanced means the cancer has spread to other parts of the body and cannot be removed with surgery. Recurrent means the cancer came back after treatment. MK-6255 is a trial medicine designed to treat advanced and recurrent EC and OC. This trial is the first time that researchers will give MK-6255 to people. The goals of this trial are to learn about: * The safety of MK-6255 and if participants tolerate it. Tolerate means participants will receive the trial medicine unless they need to stop it due to health problems. * What happens to different dose levels (amounts) of MK-6255 in the body over time.
Interventions
BIOLOGICALMK-6255
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).
OTHERCD8 PET Tracer
Participants may receive an optional CD8 PET tracer for exploratory imaging assessments.
DRUGAcetaminophen
Participants will receive acetaminophen (or similar antipyretic) as premedication.
DRUGDiphenhydramine
Participants will receive diphenhydramine (or similar antihistamine) as premedication.
DRUGDexamethasone
Participants will receive dexamethasone as premedication.
BIOLOGICALTocilizumab
Participants will receive this rescue medication at the investigator's discretion for treatment of cytokine release syndrome (CRS) after MK-6255 administration.
BIOLOGICALTocilizumab biosimilar
Participants will receive this rescue medication at the investigator's discretion for treatment of cytokine release syndrome (CRS) after MK-6255 administration.
BIOLOGICALSiltuximab
Participants will receive this rescue medication at the investigator's discretion for treatment of cytokine release syndrome (CRS) after MK-6255 administration.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed