Genes give your body instructions on how to make proteins. Proteins are needed to keep the body working properly. Many types of cancer are caused by changes in certain genes, making them faulty. Some people with solid tumors have a faulty KRAS gene. One such change in the KRAS gene is called a G12D mutation. Researchers are looking for ways to stop the actions of abnormal proteins made from the KRAS G12D mutation.
ASP3082 is thought to replace some of the abnormal proteins made from the faulty KRAS gene. If other medicines are given at the same time as ASP3082, they may affect how the body processes ASP3082.
In this study, fluconazole, itraconazole and carbamazepine are given with ASP3082 in healthy adults. The main aims are to check if fluconazole, itraconazole and carbamazepine affect how the body processes ASP3082. These medicines may affect how the body processes ASP3082 when they are taken at the same time.
This study will have 3 groups of adults. One group will be given fluconazole and ASP3082, the second group will be given carbamazepine and ASP3082, and the third group will be given itraconazole and ASP3082. ASP3082 will be given to people slowly through a tube into the vein (infusion). Fluconazole and carbamazepine will be given as a tablet and itraconazole will be given as a liquid by mouth. People will be given study treatments for about 1 month. They will then return to the clinic about 1 week after they finish study treatment for a final safety check.
Participant is healthy and has no clinically significant medical condition based on the physical examination, electrocardiograms (ECGs) and protocol-defined clinical laboratory tests at screening or on day -1.
Female participant is not pregnant and is not a woman of childbearing potential (WOCBP)
Female participant must not be breastfeeding or lactating starting at screening and throughout the investigational period and for 5 half-lives (approximately 28 days after final study intervention administration).
Female participant must not donate ova starting at first administration of study intervention and throughout the investigational period and for 3 months after final study intervention administration.
Participant is positive for Human Leukocyte Antigen (HLA) -B15:02 or HLA-A31:01, for Group 2 only.
Participant has been pregnant within 6 months prior to screening.
Participant has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal and/or other major disease.
Participant has a history of malignancy within 2 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that is considered cured with minimal risk of recurrence).
Crossover
Setidegrasib
DrugIntravenous (IV) infusion
Fluconazole
DrugOral
Carbamazepine
DrugOral
Itraconazole
DrugOral
Pharmacokinetics (PK) of ASP3082 in plasma: Maximum Concentration (Cmax) in ASP3082
Cmax will be recorded from the PK plasma samples collected.
PK of ASP3082 in plasma: area under the concentration-time curve from time zero to the time of the last measurable concentration (AUClast) in ASP3082
AUClast will be recorded from the PK plasma samples collected.
PK of ASP3082 in plasma: area under the concentration-time curve extrapolated to infinity (AUCinf) in ASP3082
AUCinf will be calculated from the PK plasma samples collected.
PK of ASP3082 in plasma: Cmax in ASP3082+ Fluconazole (FLZ)
Cmax will be recorded from the PK plasma samples collected.
Number of Participants with Adverse Events (AEs)
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. This includes events related to the comparator, if applicable, and events related to the (study) procedures.
Number of Participants with laboratory value abnormalities and/or AEs
Number of participants with potentially clinically significant laboratory values.
Number of Participants with vital sign abnormalities and/or AEs
Number of participants with potentially clinically significant vital sign values.
Number of Participants with electrocardiogram (ECG) abnormalities and/or AEs
Number of participants with potentially clinically significant ECG values.
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