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Prexasertib

Protein Kinase Inhibitors

Enzyme Inhibitors

Prexasertib intravenously (IV) on day 1 of a 14 day cycle. Treatment with prexasertib may continue until disease progression, unacceptable toxicity, or other discontinuation criteria are met.

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The primary purpose of this study is to assess the tolerability of prexasertib in Japanese participants with advanced solid cancers.

A Study of Prexasertib (LY2606368) in Japanese Participants With Advanced Cancers

A Phase 1 Study of LY2606368 in Japanese Patients With Advanced Solid Tumors

Eli Lilly and Company

Blood and Lymph Conditions

Rare Diseases

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

Antineoplastic Agents

Anti-Infective Agents

Analgesics

Etoposide

Cytarabine

Mitoxantrone

Etoposide phosphate

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

* Cytarabine is administered intravenously on days 1-5.
* Etoposide is administered intravenously on days 1-5.
* Mitoxantrone is administered intravenously on days 1-5.
* Prexasertib is administered intravenously on days 1, 3, and 5.

Standard chemotherapy (topoisomerase inhibitor)

Standard chemotherapy (topoisomerase II inhibitor)

Eric S Winer, MD

This research study is studying a targeted therapy combined with chemotherapy as a possible treatment for acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS).

The drugs involved in this study are:

* Prexasertib (LY2606368)
* Mitoxantrone
* Etoposide
* Cytarabine

This research study is a Phase I clinical trial, which tests the safety of an investigational drug or combination of drugs and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved prexasertib as a treatment for any disease. Prexasertib is a checkpoint kinase 1 (CHK1) inhibitor that is being developed as a treatment for patients with advanced cancer. CHK1 inhibitors work by preventing cancer cells from being able to repair damaged DNA (one of the building blocks of a cell) which then leads to cell death.

The drugs mitoxantrone, etoposide, and cytarabine (MEC) have all been approved by the FDA. MEC is a standard chemotherapy treatment option, commonly used for AML that has not responded to other standard treatment or returned following standard treatment.

In this research study, the investigators are combining prexasertib with MEC therapy to test if it is a safe treatment for AML or MDS that has returned or not responded to standard treatment.

Prexasertib in Combination With MEC in Relapsed/Refractory AML and High Risk MDS - a Phase I Trial

Prexasertib in Combination With Mitoxantrone, Etoposide and Cytarabine (MEC) in Relapsed/Refractory Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS) - a Phase I Trial

Toxicities occurring following administration of protocol therapy, measured using CTCAE 5.0 criteria.

Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the study drug combination.

Rates of complete remission (CR), complete remission with incomplete count recovery (CRi), and partial remission (PR).

Assess the overall survival rate for the combination.

Time of achievement of CR or CRi to relapse, death, or 1 year (whichever occurs first)

Dana-Farber Cancer Institute

Principal Investigator

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Small Cell Lung Carcinoma

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

105 mg/m\^2 Intravenous (IV) prexasertib administered of every 14 days with extensive stage disease small cell lung cancer (ED-SCLC) who had platinum-sensitive disease (has prior platinum based therapy with subsequent progression greater or less than 90 days after last dose of platinum based therapy).

105 mg/m\^2 IV prexasertib administered of every 14 days with extensive stage disease small cell lung cancer (ED-SCLC) who had resistant/refractory disease (did not have an objective response to platinum-based therapy or had progression greater than 90 days after the last dose of platinum).

40 mg/m\^2 IV prexasertib Day 1, 2, and Day 3 of a 14 day cycle in participants with ED-SCLC platinum sensitive disease.

The purpose of this study is to evaluate the safety and efficacy of prexasertib when given to participants with extensive stage disease small cell lung cancer (ED-SCLC). The study will evaluate how the body processes the drug and how the drug affects the body. The study will also evaluate the association between tumor response and the participant's perceived quality of life.

A Study of Prexasertib (LY2606368) in Participants With Extensive Stage Disease Small Cell Lung Cancer

A Phase 2 Study of LY2606368 in Patients With Extensive Stage Disease Small Cell Lung Cancer

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions

Pharmacokinetics(PK): Maximum Concentration of Prexasertib. The same dose was administered to Cohort 1 and Cohort 2 and were combined for analysis.

Pharmacokinetics(PK): Maximum Concentration of Prexasertib

Pharmacokinetics: Area Under the Concentration Curve of Prexasertib

Disease control rate (DCR) is defined as the percentage of participants achieving a best overall response of CR, PR, or SD as determined by RECIST 1.1. CR is defined as a disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \<10 mm and normalization of tumor marker results; PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters; SD is defined as neither sufficient shrinking to qualify as PR nor sufficient increase to qualify for PD.

PFS defined as the from randomization date to the first evidence of disease progression as defined by RECIST v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of first dose, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.

DoR the time from the date of an objective response until Progressive Disease (PD): was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

OS defined as from randomization date to the date of death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive.

LCSS is a 9-item questionnaire, six measuring major symptoms for lung malignancies (appetite, fatigue, cough, dyspnea, hemoptysis and pain), and 3 summation items related to total symptomatic distress, activity status and overall quality of life. Participant responses were measured using visual analogue scales (VAS) with 100-mm lines. The LCSS total score was defined as the mean of the 9 items of the scale, each scored between 0 (for best outcome) to 100 (for worst outcome).

ABSI was the mean score for the six major lung cancer symptoms (appetite, fatigue, cough, dyspnea, hemoptysis and pain), each scored between 0 (for best outcome) to 100 (for worst outcome).

All randomized participants who received at least 1 dose of study drug.

Intravenous (IV) prexasertib (LY2606368)administered on day 1 of every 14 day cycle

105 mg/m^2 Prexasertib (Platinum Sensitive Disease)

IV prexasertib (LY2606368) administered on day 1 of every 14 day cycle

105 mg/m^2 Prexasertib (Platinum Resistant Disease)

IV 40 mg/m2 prexasertib (LY2606368) IV administered on Days 1, 2 and 3 of a 14-day cycle

40 mg/m2 Prexasertib Exploratory Addendum

Prexasertib (Platinum Sensitive Disease)

Prexasertib (Platinum Resistant Disease)

IV prexasertib (LY2606368) administered on Days 1, 2 and 3 of a 14-day cycle

Prexasertib Exploratory Addendum (Platinum Sensitive Disease)

Total

Age, Continuous

Sex: Female, Male

N is number of participants with non-missing data.

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Greece

Netherlands

South Korea

Turkey

United States

Ukraine

United Kingdom

France

Germany

Spain

Region of Enrollment

Chief Medical Officer

Intravenous (IV) prexasertib (LY2606368) administered on day 1 of every 14 day cycle

Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])

Cycle 1

Cycle 3

Cycle 5

Cycle 7

105 mg/m^2 Prexasertib

All randomized participants who received at least 1 dose of study drug and had evaluable PK parameters. Cohort 1 and Cohort 2 received the same dose and were combined per protocol.

Pharmacokinetics(PK): Maximum Concentration (Cmax) of Prexasertib Cohort 1 and Cohort 2

40 mg/m2 IV prexasertib (LY2606368) administered on Days 1, 2 and 3 of a 14-day cycle

Al randomized participants with at least 1 dose of study drug, received 40 mg/m\^2 and had evaluable PK parameters.

Pharmacokinetics(PK): Maximum Concentration of Prexasertib Cohort 3 (40 mg/m^2, Protocol Addenda)

Cohort 1 Prexasertib (Platinum Sensitive Disease)

Cohort 2 Prexasertib (Platinum Resistant Disease)

Cohort 3 Prexasertib Exploratory(Platinum Sensitive Disease)

All participants in Part A1 that received at least 1 dose of study drug and had evaluable PK data.

Disease Control Rate: Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD)

All randomized participants. 4 participants were censored from Prexasertib Cohort 1 and 1 participant from Prexasertib Cohort 3.

Progression-Free Survival (PFS)

Analysis was not performed due to only 3 responders in Cohort 1, no in Cohort 2 or 3. Individual data for Cohort 1 is presented.

Duration of Response (DoR)

All randomized participants. 8 participants were censored from Cohort 1, 5 participants were censored from Cohort 2 and 4 participants censored from Cohort 3.

Overall Survival (OS)

All participants in Cohort 1 and Cohort 2. Cohort 3 was added by protocol addendum and data were not collected with non missing baseline and post baseline scores.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Prexasertib (LY2606368) in Japanese Participants With Advanced Cancers	NCT02514603	Neoplasm	Prexasertib	20 Years -	Eli Lilly and Company
Prexasertib in Combination With MEC in Relapsed/Refractory AML and High Risk MDS - a Phase I Trial	NCT03735446	Acute Myeloid L... Myelodysplastic...	Prexasertib Mitoxantrone Etoposide Cytarabine	18 Years -	Dana-Farber Cancer Institute
A Study of Prexasertib (LY2606368) in Participants With Extensive Stage Disease Small Cell Lung Cancer	NCT02735980	Small Cell Lung...	Prexasertib	18 Years -	Eli Lilly and Company
A Study of Prexasertib (LY2606368) in Participants With Extensive Stage Disease Small Cell Lung Cancer	NCT02735980	Small Cell Lung...	Prexasertib	18 Years -	Eli Lilly and Company

Spots Global Cancer Trial Database for chk1

Every month we try and update this database with for chk1 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 chk1

Every month we try and update this database with for chk1 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 chk1 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.