Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

All Conditions

Rare Diseases

Wilms Tumor

Wilms' Tumor

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants will receive ASP7517 on Day 1 of each 28-day cycle for up to 6 doses.

Participants will receive ASP7517 on Day 1 of each 28-day cycle for up to 6 doses in combination with up to 4 doses of pembrolizumab administered every 6 weeks starting from Cycle 1 Day 1. Pembrolizumab monotherapy may be extended up to a total of 17 doses for qualifying participants.

Participants will receive RP2D of ASP7517 on Day 1 of each 28-day cycle for up to 6 doses

Participants will receive RP2D of ASP7517 on Day 1 of each 28-day cycle for up to 6 doses in combination with up to 4 doses of pembrolizumab administered every 6 weeks. Pembrolizumab monotherapy may be extended up to a total of 17 doses for qualifying participants.

ASP7517

Medical Director

The purpose of this study is to evaluate the safety, tolerability, and clinical response of ASP7517, and determine the Recommended Phase 2 Dose (RP2D) and/or the Maximum Tolerated Dose (MTD) of ASP7517 when administered as a single agent and in combination with pembrolizumab.

This study will also evaluate other measures of anticancer activity of ASP7517 when administered as a single agent and in combination with pembrolizumab based on central and local assessment.

This study consists of arms receiving ASP7517 monotherapy and arms receiving ASP7517 and pembrolizumab combination therapy in Phase 1 (dose escalation cohort) and Phase 2 (dose expansion cohort). Phase 2 monotherapy and combination dose expansion cohorts will be opened after the phase 1 escalation cohort has been completed.

Study of ASP7517 Alone and With Pembrolizumab in Participants With Advanced Solid Tumors Expressing WT1 Antigen

A Phase 1/2, Open-label Study Investigating the Safety, Tolerability and Efficacy of ASP7517 as a Single Agent and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors Known to Express WT1 Antigen

Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.

Events below occurring within 28 days of first dose on Cycle 1 Day 1 (C1D1) and considered related to IP.

Monotherapy:

Non-hematologic AEs grade \>= 3 not resolving to Grade \<=2 within 72 hours of onset; Confirmed Hy's law; Infusion-related reaction (IRR) requiring infusion discontinuation; Treatment-related toxicity with \> 2 weeks delay in initiating Cycle 2 or discontinuation during Cycle 1; Grade \>= 3 anemia requiring transfusion or thrombocytopenia with bleeding requiring transfusion/hospitalization; Grade 3 febrile neutropenia with/without infection; Grade 5 treatment-related toxicity

Combination Therapy:

DLTs mentioned above; Grade \>= 2 pneumonitis, encephalopathy, meningitis, motor/sensory neuropathy; Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 5 x upper limit of normal (ULN) in absence of liver metastases; AST or ALT \> 8 x ULN in presence of liver metastases; Total bilirubin \> 3 x ULN; Guillain-Barre syndrome/myasthenic syndrome/myasthenia gravis

An AE is any untoward medical occurrence in a participant temporally associated with the use of study IP and other study treatments, whether or not considered related to the study IP and other study treatments. 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 IP and other study treatments. This includes events related to the comparator and events related to the (study) procedures. AEs will be graded using NCI-CTCAE guidelines, version 5.0.

An AE is considered "serious" if the event: results in death; is life threatening; requires inpatient hospitalization or leads to prolongation of hospitalization; results in persistent or significant disability/incapacity; results in congenital anomaly/birth defect; other medically important events.

Number of participants with potentially clinically significant laboratory values.

Number of participants with potentially clinically significant 12-lead ECG values.

Number of participants with potentially clinically significant vital sign values.

Number of participants with potentially clinically significant physical exam values.

The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 5 (dead). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.

iORR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed modified Complete Response (iCR) or modified Partial Response (iPR) per iRECIST by independent central review.

ORR is defined as the proportion of participants for each dose level whose best overall response is rated as Complete Response (CR) or Partial Response (PR) per RECIST v1.1.

iDCR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed iCR, iPR or stable disease (iSD), per iRECIST.

DCR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed CR, PR or SD per RECIST v1.1.

iPFS is defined as the time from the start of the study treatment until death from any cause or radiographic disease progression assessed per iRECIST by independent central review.

iPFS is defined as the time from the start of the study treatment until death from any cause or radiographic disease progression assessed per iRECIST by investigator assessment.

PFS is defined as the time from the start of the study treatment until death from any cause or radiographic disease progression assessed per RECIST v1.1 by independent central review.

PFS is defined as the time from the start of the study treatment until death from any cause or radiographic disease progression assessed per RECIST v1.1 by investigator assessment.

OS is defined as the time from the date of first dose until the date of death from any cause.

iDOR will be calculated only for the subgroup of participants with confirmed response iCR/iPR per iRECIST by independent central review.

iDOR will be calculated only for the subgroup of participants with confirmed response iCR/iPR per iRECIST by investigator assessment.

DOR will be calculated only for the subgroup of participants with confirmed response CR/PR per RECIST v1.1 by independent central review.

DOR will be calculated only for the subgroup of participants with confirmed response CR/PR per RECIST v1.1 by investigator assessment.

Astellas Pharma Global Development, Inc.

Symptoms and General Pathology

Blood and Lymph Conditions

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Neoplasms by Histologic Type

Hematologic Diseases

Bone Marrow Diseases

Precancerous Conditions

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Two single doses of ASP7517 will be administered intravenously at up to 3 dose levels and will be based on the assessment of safety variables, including the occurrence of dose limiting toxicities (DLTs).

Up to six single doses of ASP7517 will be administered intravenously at the dose levels determined from the Dose Escalation phase.

The purpose of this study is to evaluate the safety and tolerability and to determine the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD) of ASP7517.

This study will also evaluate the clinical response of ASP7517 as well as other measures of anticancer activity of ASP7517.

This study consists of 2 parts: phase 1 dose escalation and phase 2 dose expansion.

Phase 1 Dose Escalation:

Approximately 18 subjects with either relapsed/refractory (R/R) AML or R/R higher risk MDS will be enrolled. Participants will receive 2 single doses of ASP7517 via intravenous infusion. Dosing will occur on day 1 of each cycle. Each cycle is defined as 28 days with a total of 2 treatment cycles.

Participants must be managed under hospitalization for at least 7 days during the first cycle of the dose escalation phase. In addition, prior to hospital discharge, participant safety must be ensured by performing medical tests and procedures listed on day 7 of cycle 1 and tests considered clinically necessary to evaluate the participant's general condition and adverse event (AE) resolution. The participant should also be followed on an outpatient basis on planned visits during cycles 1 and 2 after hospital discharge during the dose limiting toxicity (DLT) assessment period to closely monitor any AEs. Participants may be hospitalized days 1 to 7 during cycle 2.

Phase 2 Dose Expansion:

Approximately 104 participants per dose level will be enrolled. Each dose level may enroll up to 52 R/R AML participants and up to 52 R/R higher risk MDS participants. Both groups of participants will enroll in parallel and independently. The number of dose levels investigated during phase 2 will be based upon the data from phase 1. When escalation and expansion cohorts are both open for enrollment, enrollment into escalation cohorts takes priority such that participants who are eligible for both will be preferentially enrolled in the escalation cohorts.

A Study Investigating the Safety, Tolerability and Efficacy of ASP7517 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML) and Relapsed/Refractory Higher Risk Myelodysplastic Syndrome (MDS)

A Phase 1/2 Open-label Study Investigating the Safety, Tolerability and Efficacy of ASP7517 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML) and Relapsed/Refractory Higher Risk Myelodysplastic Syndrome (MDS)

A DLT is defined as any of the following events that occur within 28 days starting with the first dose on cycle 1 day 1 (C1D1) and that is considered to be related to investigation product (IP). The severity of AEs will be assessed according to National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. DLT is defined as follows: non-hematologic AEs that are ≥ grade 3; confirmed Hy's law case; new onset of grade 4 thrombocytopenia (with minimum of 2 grade worsening from baseline) within 24 hours of dosing; prolonged myelosuppression, defined as absolute neutrophil count (ANC) \< 500/μL for more than 28 days off therapy and in the absence of evidence of active leukemia or MDS in the marrow or blood, will be considered as a DLT.

An AE is any untoward medical occurrence in a participant administered a study drug, and which does not necessarily have to have a causal relationship with this treatment. 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 a medicinal product whether or not considered related to the medicinal product. AEs will be graded using NCI-CTCAE guidelines, version 5.0.

An AE is considered "serious" if the event: results in death; is life-threatening (An AE is considered "life-threatening" if its occurrence places the subject at immediate risk of death; it does not include an AE that, had it occurred in a more severe form, might have caused death.); results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly, or birth defect; requires inpatient hospitalization (except for planned procedures as allowed per study) or leads to prolongation of hospitalization (except if prolongation of planned hospitalization is not caused by an AE); other medically important events.

Routine 12-lead ECGs will be taken after the subject has been resting in the supine position for at least 5 minutes. Routine 12-lead ECGs will be taken in triplicate during the Screening and Treatment Periods, and as a single assessment (in triplicate, if deemed necessary) during the Observation Periods 1 and 2.

CRc rate is defined for AML subjects as the number of participants who achieve the best response of CRc (complete remission \[CR\], complete remission with incomplete platelet recovery \[CRp\] or complete remission with incomplete hematological recovery \[CRi\]) divided by the number of participants in the analysis population.

CR + BM CR + PR rate is defined for MDS participants as the number of participants who achieve the best response of CR + BM CR + PR divided by the number of subjects in the analysis population.

Duration of remission for participants with AML includes duration of CRc, duration of CR/complete remission with partial hematologic recovery (CRh), duration of CRh, duration of CR, and duration of response (i.e., CRc + PR).

Duration of remission for MDS includes duration of CR and duration of response (i.e., CR + PR).

EFS is defined as the time from the date of first dose until the date of documented relapse, treatment failure or death from any cause within 30 days after the last dose of study drug (whichever occurs first earliest of \[relapse date, treatment failure date, death date\] - first dose date + 1).

OS is defined as the time from the date of first dose until the date of death from any cause (death date - first dose date + 1).

CR rate is defined as the number of participants who achieve CR at any of the postbaseline visits divided by the number of participants in the analysis population.

Best response rate is defined as the number of subjects who achieve CRc or PR at any of the postbaseline visits divided by the number of subjects in the analysis population.

CRh rate is defined as the number of participants who achieve CRh at any of the postbaseline visits divided by the number of participants in the analysis population.

HI requires 1 measurement of erythroid or platelets or neutrophils maintained at a specified level for at least 8 weeks without ongoing cytotoxic therapy

Objective response (CR + BM CR + PR + HI) rates (ORR) for participants with R/R higher risk MDS \[Time Frame: Up to 2 years\] ORR is defined as the number of participants who achieve CR or BM CR or PR or HI at any of the postbaseline visits divided by the number of participants in the analysis population.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of ASP7517 Alone and With Pembrolizumab in Participants With Advanced Solid Tumors Expressing WT1 Antigen	NCT04837196	Advanced Malign... Advanced Cancer	ASP7517 Pembrolizumab	18 Years -	Astellas Pharma Inc
A Study Investigating the Safety, Tolerability and Efficacy of ASP7517 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML) and Relapsed/Refractory Higher Risk Myelodysplastic Syndrome (MDS)	NCT04079296	Acute Myeloid L... Myelodysplastic...	ASP7517	18 Years -	Astellas Pharma Inc
A Study Investigating the Safety, Tolerability and Efficacy of ASP7517 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML) and Relapsed/Refractory Higher Risk Myelodysplastic Syndrome (MDS)	NCT04079296	Acute Myeloid L... Myelodysplastic...	ASP7517	18 Years -	Astellas Pharma Inc
Study of ASP7517 Alone and With Pembrolizumab in Participants With Advanced Solid Tumors Expressing WT1 Antigen	NCT04837196	Advanced Malign... Advanced Cancer	ASP7517 Pembrolizumab	18 Years -	Astellas Pharma Inc

Spots Global Cancer Trial Database for asp7517

Every month we try and update this database with for asp7517 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for asp7517

Every month we try and update this database with for asp7517 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for asp7517 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.