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

Study Overview
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Brief Summary
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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.

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

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Prexasertib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have ED-SCLC and have received a prior platinum-based regimen Participants in Cohort 1 and in the addendum must have had an objective response to prior platinum-based therapy with subsequent progression ≥90 days after the last dose of platinum Participants in Cohort 2 must have either not had an objective response to prior platinum based therapy or had progression <90 days after the last dose of platinum Have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group scale Exclusion Criteria: Have received more than 2 prior therapies for ED-SCLC (including immunotherapy, targeted therapies, or chemotherapy) Have symptomatic central nervous system (CNS) malignancy or metastasis. Asymptomatic participants with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids to treat CNS metastases Have previously completed or withdrawn from this study or any other study investigating prexasertib or a checkpoint kinase I (CHK1) inhibitor or have shown hypersensitivity to any of the components of the prexasertib formulation Have a serious cardiac condition

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prexasertib (Platinum Sensitive Disease)<br>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). | Drug: Prexasertib<br>* Administered IV<br>* Other names: LY2606368;|
| Experimental: Prexasertib (Platinum Resistant Disease)<br>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). | Drug: Prexasertib<br>* Administered IV<br>* Other names: LY2606368;|
| Experimental: Prexasertib Exploratory Addendum (Platinum Sensitive Disease)<br>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. | Drug: Prexasertib<br>* Administered IV<br>* Other names: LY2606368;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) | 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 | Baseline to 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics(PK): Maximum Concentration (Cmax) of Prexasertib Cohort 1 and Cohort 2 | Pharmacokinetics(PK): Maximum Concentration of Prexasertib. The same dose was administered to Cohort 1 and Cohort 2 and were combined for analysis. | Cycle 1,3, 5, and 7: Day 1, Day 2 and Day 3- Prior to start of infusion, end of infusion plus 10 minutes, Day 8: anytime | 
| Pharmacokinetics(PK): Maximum Concentration of Prexasertib Cohort 3 (40 mg/m^2, Protocol Addenda) | Pharmacokinetics(PK): Maximum Concentration of Prexasertib | Cycle 1,3, 5, and 7: Day 1, Day 2 and Day 3- Prior to start of infusion, end of infusion plus 10 minutes, Day 8: anytime | 
| Pharmacokinetics: Area Under the Concentration Curve of Prexasertib | Pharmacokinetics: Area Under the Concentration Curve of Prexasertib | Cycle 1,3, 5, and 7: Day 1, Day 2 and Day 3- Prior to start of infusion, end of infusion plus 10 minutes, Day 8: anytime | 
| Disease Control Rate: Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD) | 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. | Baseline through Disease Progression or Death from Any Cause to 28 months | 
| Progression-Free Survival (PFS) | 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. | Baseline to Disease Progression or Death (up to 9 months) | 
| Duration of Response (DoR) | 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. | Date of CR or PR to Date of Disease Progression or Death Due to Any Cause up to 9 months | 
| Overall Survival (OS) | 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. | Baseline up to 28 months | 
| Change From Baseline in Lung Cancer Symptom Scale Score (LCSS) | 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). | Baseline up to 9 months | 
| Change From Baseline on the Average Symptom Burden Index (ASBI) | 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). | Baseline up to 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCLC, LY2606368, CHK1