Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Adjuvants, Anesthesia

Central Nervous System Depressants

Psychotropic Drugs

All Drugs and Chemicals

Midazolam

Anesthetics

Hypnotics and Sedatives

Anti-Anxiety Agents

Anesthetics, Intravenous

Anesthetics, General

GABA Modulators

Neurotransmitter Agents

LY3295668 erbumine administered orally (Part I).

Approximately the first 10 participants enrolled in this arm will be administered midazolam.

LY3295668 erbumine administered orally and endocrine therapy administered according to package label (Part II).

LY3295668 erbumine administered orally and endocrine therapy administered according to package label (Part I).

LY3295668 Erbumine

Administered according to label instructions.

Endocrine therapy

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

The reason for this study is to determine the recommended phase 2 dose of the study drug LY3295668 erbumine in participants with breast cancer that has spread to other parts of the body.

A Study of LY3295668 Erbumine in Participants With Breast Cancer That Has Spread to Other Parts of the Body

A Phase 1b Study of Aurora A Kinase Inhibitor LY3295668 Erbumine in Monotherapy and Combination Therapy in Patients With Metastatic Breast Cancer Post CDK4/6 Inhibitor and Endocrine Therapy

Number of Participants with Dose Reductions

Part II: Number of Participants with DLTs

PK: AUC of LY3295668 in Combination with Endocrine Therapy

PK: AUC of Endocrine Therapy in Combination with LY3295668

PK: AUC of Midazolam in Combination with LY3295668

Eli Lilly and Company

Blood and Lymph Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Hematologic Neoplasms

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

The dose escalation will be conducted in 2 parts. Group 1 will consist of 8 cohorts and Group 2 will consist of 5 cohorts. The dose escalation is aimed at determining the maximum tolerated dose (MTD) of AMG 900.

The dose expansion part of the study will begin after completion of the dose escalation phase and will consist of 20 subjects with acute myelogenous leukemia.

AMG 900 is a small molecule aurora kinase inhibitor. AMG 900 will be administered daily for 4 days every 2 weeks or daily 7 days every 2 weeks (ie.g., 4 consecutive days of dosing followed by 10 consecutive days off treatment).

Arm 1- Dose Escalation

AMG 900 is a small molecule aurora kinases inhibitor. The dose expansion phase would be conducted to gain further clinical experience with AMG 900 in AML at the optimal dose schedule.

Arm 2- Dose Expansion

This study of AMG 900 will be conducted in two parts: dose escalation and dose expansion. The dose escalation part of the study is aimed at evaluating the safety, tolerability and PK (pharmacokinetics) of oral AMG 900 in subjects with acute myeloid leukemia. Up to 93 subjects may be enrolled in dose escalation. The dose expansion part of the study will consist of 20 subjects with acute myeloid leukemia. The dose of AMG 900 will be dependent upon data from the dose escalation part of the study.

Study Evaluating Orally Administered AMG 900 in Adult Subjects With Acute Myeloid Leukemia

A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally Administered AMG 900 in Adult Subjects With Acute Myeloid Leukemia

Amgen

Antineoplastic Agents

Taxane

Complement System Proteins

Complement Factor H

Immunosuppressive Agents

Immunologic Factors

The dose expansion part of the study will begin after completion of the dose escalation phase and will consist of 3 cohorts of 14 subjects each. One taxane-resistant tumor type will be evaluated in each cohort.

The dose escalation part of the study is aimed at determining the maximum tolerated dose (MTD) of AMG 900 and if necessary, the MTD with prophylactic GCSF support (MTD-G).

AMG 900 is a small molecule inhibitor of aurora kinases A, B and C. AMG 900 will be administered daily for 4 days every 2 weeks (i.e., 4 consecutive days of dosing followed by 10 consecutive days off treatment).

Arm 1- Dose Expansion

This first-in-human study of AMG 900 will be conducted in two parts: dose escalation and dose expansion. The dose escalation part of the study is aimed at evaluating the safety, tolerability and PK of oral AMG 900 in subjects with advanced solid tumors. Up to 50 subjects may be enrolled in dose escalation. The dose expansion part of the study will consist of 42 subjects in three taxane-resistant tumor types. The dose of AMG 900 will be dependent upon data from the dose escalation part of the study

that G-CSF must be started at day 5, 1 day after the last day of AMG 900 and be continued until neutrophiles are \> 1000 or until day 12, meaning 2 days before the reinduction.

A Phase 1 First-in-Human Study Evaluating AMG 900 in Advanced Solid Tumors

A Phase 1, First-in-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally Administered AMG 900 in Adult Subjects With Advanced Solid Tumors

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antirheumatic Agents

Cyclophosphamide

Topotecan

Antineoplastic Agents, Alkylating

Alkylating Agents

Topoisomerase I Inhibitors

Enzyme Inhibitors

LY3295668 Erbumine given orally and topotecan and cyclophosphamide given intravenously (IV).

LY3295668 Erbumine given orally and topotecan and cyclophosphamide given IV.

The reason for this study is to see if the study drug LY3295668 erbumine is safe in participants with relapsed/refractory neuroblastoma.

A Study of LY3295668 Erbumine in Participants With Relapsed/Refractory Neuroblastoma

A Phase 1 Study of Aurora Kinase A Inhibitor LY3295668 Erbumine as a Single Agent and in Combination in Patients With Relapsed/Refractory Neuroblastoma

PK: AUC of LY3295668 in Combination with topotecan and cyclophosphamide

New Approaches to Neuroblastoma Therapy Consortium (NANT)

Innovative Therapies for Children with Cancer in Europe (ITCC)

Regimen 1: AS703569 administered on Days 1, 2, 3 and Days 8, 9, 10 of a 21-day cycle

Regimen 2: AS703569 administered on Days 1, 2, 3, 4, 5, 6 of a 21-day cycle

Dose Escalation

Regimen 1 - 3-47 mg/m2/day, orally once daily on days 1, 2,3 and 8, 9, 10 of a 21 day cycle:

Number of cycles: until progression or unacceptable toxicity develops.

Cohort Expansion

Regimen 1 - Maximum tolerated dose from dose-escalation part or a lower dose in mg/m2/day, orally once daily on days 1, 2,3 and 8, 9, 10 of a 21 day cycle:

Number of cycles: until progression or unacceptable toxicity develops

AS703569

Dose Escalation Regimen 2 - 3-47 mg/m2/day, orally once daily on days 1, 2, 3, 4, 5, 6 of a 21 day cycle Number of cycles: until progression or unacceptable toxicity develops.

Cohort Expansion Regimen 2 - Maximum tolerated dose from dose-escalation part or a lower dose in mg/m2/day, orally once daily on days 1, 2, 3, 4, 5, 6 of a 21 day cycle Number of cycles: until progression or unacceptable toxicity develops.

Narmyn Rejeb, M.D.

EMD Serono decided to terminate enrollment based on a review of the available clinical data and low probability of completing the trial based on the observed recruitment rate. Subjects already enrolled in the study continued participation in the study, consistent with the protocol, to study completion.

The goal of this research study is to investigate for the first time the safety and tolerability of a new drug (AS703569), called an aurora kinase inhibitor, being tested to treat blood cancers in patients with different blood cancers. The research study will also assess how the body breaks down AS703569 and what changes occur in the blood after oral doses of AS703569. It will also look to see if there is any improvement in your blood cancer. The use of AS703569 in this study is experimental.

A Phase I, Dose-escalation Study of AS703569 Given Orally to Subjects With Haematological Malignancies

Dose-escalation part - The number of subjects experiencing at least a Dose-Limiting Toxicity (DLT), judged to be related to the study medication, evaluated over the first cycle only for each dose level and regimen, independently.

Cohort expansion part - Preliminary anti-tumour activity in four selected cohorts of haematological malignancies as assessed every two cycles

Dose-escalation and Cohort expansion parts The proportion/number of subjects experiencing treatment-emergent adverse events (TEAE) after the first cycle and during multiple cycles, in each cohort for each of the 2 dose-regimens.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of LY3295668 Erbumine in Participants With Breast Cancer That Has Spread to Other Parts of the Body	NCT03955939	Metastatic Brea...	LY3295668 Erbum... Endocrine thera... Midazolam	18 Years -	Eli Lilly and Company
Study Evaluating Orally Administered AMG 900 in Adult Subjects With Acute Myeloid Leukemia	NCT01380756	Cancer Hematologic Mal... Leukemia Myeloid Leukemi...	Arm 1- Dose Esc... Arm 2- Dose Exp...	18 Years -	Amgen
A Study of LY3295668 Erbumine in Participants With Breast Cancer That Has Spread to Other Parts of the Body	NCT03955939	Metastatic Brea...	LY3295668 Erbum... Endocrine thera... Midazolam	18 Years -	Eli Lilly and Company
A Phase 1 First-in-Human Study Evaluating AMG 900 in Advanced Solid Tumors	NCT00858377	Advanced Malign... Advanced Solid ... Cancer Solid Tumors Tumors	Arm 1- Dose Esc... Arm 1- Dose Exp...	18 Years -	Amgen
A Study of LY3295668 Erbumine in Participants With Relapsed/Refractory Neuroblastoma	NCT04106219	Neuroblastoma	LY3295668 Erbum... Topotecan Cyclophosphamid...	2 Years - 21 Years	Eli Lilly and Company
A Phase I, Dose-escalation Study of AS703569 Given Orally to Subjects With Haematological Malignancies	NCT01080664	Haematological ...	AS703569 AS703569	18 Years -	EMD Serono

Spots Global Cancer Trial Database for aurora kinase inhibitor