A Study of Rovalpituzumab Tesirine to Study Cardiac Ventricular Repolarization in Subjects With Small Cell Lung Cancer

Study Overview
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Brief Summary
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Study to evaluate the effect of rovalpituzumab tesirine on cardiac ventricular repolarization in subjects with small cell lung cancer (SCLC).

Official Title
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An Intensive QT/QTc Study to Investigate the Effects of Rovalpituzumab Tesirine on Cardiac Ventricular Repolarization in Subjects With Small Cell Lung Cancer

Conditions
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Small Cell Lung Carcinoma

Intervention / Treatment
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* Drug: Rovalpituzumab Tesirine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed extensive-stage small-cell lung cancer (SCLC). Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Adequate hematologic and organ function as confirmed by laboratory values Exclusion Criteria: Clinically significant cardiac abnormalities including QRS duration of >120 msec; QTcF >470 msec for women and >450 msec for men; Abnormal cardiac rhythm; Clinically significant cardiac valve abnormality; Documented history of left ventricular ejection fraction <0.30 within 6 months; Permanent pacemaker or automatic implantable cardioverter defibrillator; History of torsades de pointes, congenital long QT syndrome, or family history of long QT syndrome or sudden death Recent or ongoing serious infection Women who are pregnant or breastfeeding Prior exposure to a pyrrolobenzodiazepine (PBD)-based drug, prior participation in a rovalpituzumab tesirine clinical trial, or known hypersensitivity to rovalpituzumab tesirine or excipient contained in the drug formulation.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rovalpituzumab Tesirine<br>0.3 mg/kg rovalpituzumab tesirine intravenously on Day 1 of every 6-week treatment cycle for 2 cycles omitting every third cycle | Drug: Rovalpituzumab Tesirine<br>* Rovalpituzumab tesirine is a DLL3 targeted antibody drug conjugate (ADC)<br>* Other names: SC16LD6.5;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in QTcF interval from baseline QTcF following treatment with rovalpituzumab teserine as measured by extracting quantitative ECG parameters from ambulatory Holter monitors. |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in RR interval from baseline RR following treatment with rovalpituzumab teserine as measured by extracting quantitative ECG parameters from ambulatory Holter monitors. |  | 12 weeks | 
| Change in PR interval from baseline PR following treatment with rovalpituzumab teserine as measured by extracting quantitative ECG parameters from ambulatory Holter monitors. |  | 12 weeks | 
| Change in QRS duration interval from baseline QRS duration following treatment with rovalpituzumab teserine as measured by extracting quantitative ECG parameters from ambulatory Holter monitors. |  | 12 weeks | 
| Change in waveform composition interval from baseline waveform composition following treatment with rovalpituzumab teserine as measured by extracting quantitative ECG parameters from ambulatory Holter monitors. |  | 12 weeks | 
| Relationship between plasma rovalpituzumab tesirine concentration and change in QTcF interval from baseline. |  | 12 weeks | 
| Incidence of proarrhythmic adverse events stratified by change in QTcF from baseline of less than 10 ms or greater than 10 ms. |  | 12 weeks | 
| Incidence of adverse events. |  | From first dose through 30 days post-last-dose | 
| Objective response rate |  | Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 24 months. | 
| Duration of response |  | Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 24 months. | 
| Progression free survival |  | Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 24 months. | 
| Overall survival |  | Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 24 months. | 
| Clinical benefit ratio |  | Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 24 months. | 
| Maximum Plasma Concentration (Cmax) |  | Cycles 1 and 2: Day 1 (predose, 30 min, 2 and 4 hours postdose) and days 2,3,4,8,15,and 29; Cycles 4,5,7,8: Day 1 predose and 30 min postdose. | 
| Area Under the Curve (AUC) |  | Cycles 1 and 2: Day 1 (predose, 30 min, 2 and 4 hours postdose) and days 2,3,4,8,15,and 29; Cycles 4,5,7,8: Day 1 predose and 30 min postdose. |