protocolSection identificationModule nctId: NCT06364696, orgStudyIdInfo id: 4396-CL-0101, briefTitle: A Study to Find a Suitable Dose of ASP4396 in Adults With Solid Tumors, statusModule overallStatus: RECRUITING, startDateStruct date: 2024-04-16, primaryCompletionDateStruct date: 2027-04-30, completionDateStruct date: 2027-04-30, studyFirstPostDateStruct date: 2024-04-15, lastUpdatePostDateStruct date: 2024-04-29, sponsorCollaboratorsModule leadSponsor name: Astellas Pharma Inc, class: INDUSTRY, descriptionModule briefSummary: Genes contain genetic code which tell the body which proteins to make. Some types of cancer are caused by changes, or mutations, in a gene called KRAS. Researchers are looking for ways to stop the actions of abnormal proteins made from the mutated KRAS gene. The so-called G12D mutation in the KRAS gene is common in people with some solid tumors.ASP4396 is being developed as a potential new treatment for solid tumors in people who have the G12D mutation in their KRAS gene. ASP4396 is not currently available as a treatment for the public. In this study, researchers will learn how ASP4396 is processed by and acts upon the body. This information will help find a suitable dose and to check for potential medical problems from ASP4396.In this study, ASP4396 is being given to humans for the first time.People in this study will be adults with locally advanced (unresectable), or metastatic solid tumors with the G12D mutation in their KRAS gene. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body. They may have been previously treated with standard therapies or refused to receive those treatments.The main aims of the study are to check the safety of ASP4396, how well people cope with medical problems during the study (how well it is tolerated), and to find a suitable dose of ASP4396.This is an open-label study. This means that people in this study and clinic staff will know that they will receive ASP4396.This study will be in 2 parts.Part 1 is called Dose Escalation. Different small groups of people will receive lower to higher doses of ASP4396. For each dose, all medical problems will be recorded. The first group will receive the lowest dose of ASP4396. A medical expert panel will check the results and decide if the next group can receive a higher dose of ASP4396. The panel will do this until all groups have taken ASP4396 or until suitable doses have been selected for Part 2.Part 2 is called Dose Expansion. Other different small groups of people will receive ASP4396 with the most suitable doses worked out from Part 1. This will help find a more accurate dose of ASP4396 to use in future studies.In both parts of the study, ASP4396 will be given through a vein. This is called an infusion. Each treatment cycle is 21 days long. People will continue treatment until: they have medical problems from the treatment they can't cope with (can't tolerate); their cancer gets worse; they start other cancer treatment; or they ask to stop treatment.People will visit the clinic on certain days during their treatment, with extra visits during the first 2 cycles of treatment. The study doctors will check for any medical problems from ASP4396. Also, people in the study will have a health check including blood tests. On some visits they will also have scans to check for any changes in their cancer. Tumor samples will be taken at certain visits during treatment with the option of a tumor sample being taken after treatment has finished.People will visit the clinic about 7 days after they stop treatment. They will be asked about any medical problems and will have a health check including blood tests.After this, people will visit the clinic for a health check several times. The number of visits and checks done at each visit will depend on the health of each person and whether they completed their treatment or not.After treatment has finished, people in the study will be followed up for up to 45 weeks., conditionsModule conditions: Solid Tumor, designModule studyType: INTERVENTIONAL, phases: PHASE1, designInfo allocation: NON_RANDOMIZED, interventionModel: SEQUENTIAL, primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 175, type: ESTIMATED, armsInterventionsModule interventions name: ASP4396, outcomesModule primaryOutcomes measure: Incidence of Dose Limiting Toxicities (DLTs) for ASP4369, primaryOutcomes measure: Number of Participants with Adverse Events (AEs), primaryOutcomes measure: Number of Participants with Serious Adverse Events (SAEs), primaryOutcomes measure: Number of Participants with laboratory value abnormalities and/or AEs, primaryOutcomes measure: Number of Participants with electrocardiogram (ECG) abnormalities and/or AEs, primaryOutcomes measure: Number of Participants with vital sign abnormalities and/or AEs, primaryOutcomes measure: Number of Participants with physical exam abnormalities and/or AEs, primaryOutcomes measure: Number of Participants with Eastern Cooperative Oncology Group (ECOG) performance status score, secondaryOutcomes measure: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, secondaryOutcomes measure: Duration of Response (DOR) per RECIST v 1.1, secondaryOutcomes measure: Disease Control Rate (DCR) per RECIST v 1.1, secondaryOutcomes measure: Progression Free Survival (PFS) per RECIST v1.1, secondaryOutcomes measure: Overall Survival (OS), secondaryOutcomes measure: Pharmacokinetics (PK) of ASP4396 in plasma: area under the concentration-time curve from the time of dosing to 24 hours after dosing (AUC24h), secondaryOutcomes measure: PK of ASP4396 metabolite in plasma: AUC24h, secondaryOutcomes measure: PK of ASP4396 in plasma: AUC168h, secondaryOutcomes measure: PK of ASP4396 metabolite in plasma: AUC168h, secondaryOutcomes measure: PK of ASP4396 in plasma: Maximum Concentration (Cmax), secondaryOutcomes measure: PK of ASP4396 metabolite in plasma: Cmax, secondaryOutcomes measure: PK of ASP4396 in plasma: concentration immediately prior to dosing at multiple dosing (Ctrough), secondaryOutcomes measure: PK of ASP4396 metabolite in plasma: Ctrough, secondaryOutcomes measure: PK of ASP4396 in plasma: Time of maximum concentration (tmax), secondaryOutcomes measure: PK of ASP4396 metabolite in plasma: tmax, secondaryOutcomes measure: Change from baseline of Kirsten rat sarcoma viral oncogene homolog (KRAS) G12D amino acid substitution (G12D) tumor samples, eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: START Midwest, status: RECRUITING, city: Grand Rapids, state: Michigan, zip: 49546, country: United States, geoPoint lat: 42.96336, lon: -85.66809, locations facility: NEXT Oncology Dallas, status: RECRUITING, city: Irving, state: Texas, zip: 75039, country: United States, geoPoint lat: 32.81402, lon: -96.94889, locations facility: START Mountain Region, status: RECRUITING, city: West Valley City, state: Utah, zip: 84119, country: United States, geoPoint lat: 40.69161, lon: -112.00105, locations facility: NEXT Oncology Virginia, status: RECRUITING, city: Fairfax, state: Virginia, zip: 22031, country: United States, geoPoint lat: 38.84622, lon: -77.30637, hasResults: False