Study Evaluating the Safety of Rovalpituzumab Tesirine for Third-Line and Later Treatment of Subjects With Relapsed or Refractory Small Cell Lung Cancer

Study Overview
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Brief Summary
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A single-arm, open-label study to assess the overall safety of rovalpituzumab tesirine in participants with relapsed or refractory delta-like protein 3 (DLL3) expressing small cell lung cancer by evaluating the frequency of high grade (>= Grade 3) select treatment-emergent adverse events (TEAEs).

Official Title
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Open-Label, Single Arm, Phase 3b Study Evaluating the Safety of Rovalpituzumab Tesirine for Third-Line and Later Treatment of Subjects With Relapsed or Refractory DLL3 Expressing Small Cell Lung Cancer

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Dexamethasone
* Drug: Rovalpituzumab tesirine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Minimum life expectancy of at least 12 weeks. Laboratory values meeting the criteria specified in the protocol. Histologically or cytologically confirmed Small Cell Lung Cancer (SCLC) with documented disease progression after at least 2 prior systemic regimens, including at least one platinum-based regimen. Delta-Like Protein 3 (DLL3)-expressing SCLC based on central immunohistochemistry (IHC) assessment of banked or otherwise representative tumor tissue. Measurable disease as described per protocol. In participants with a history of central nervous system (CNS) metastases, documentation of stable or improved status based on brain imaging for at least 2 weeks after completion of definitive treatment and within 2 weeks prior to first dose of study drug, off or on a stable dose of corticosteroids. Exclusion Criteria: Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association Class III - IV within 6 months prior to first dose of study drug. Recent or on-going serious infection. History of other invasive malignancy that has not been in remission for at least 3 years. History of exposure to a pyrrolobenzodiazepine (PBD)-based drug or known hypersensitivity to rovalpituzumab tesirine or excipient contained in the drug formulation. Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells. Documented history of capillary leak syndrome. Grade 2 or higher pleural or pericardial effusion within 4 weeks of investigational drug start, or earlier history of recurrent Grade 2 or higher effusions with ongoing requirements for pericardiocentesis or thoracentesis.

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 + dexamethasone<br>Rovalpituzumab tesirine 0.3 mg/kg administered intravenously on Day 1 of each 6-week cycle plus oral dexamethasone 8 mg twice daily on Day -1, Day 1, and Day 2 of 6-week each cycle. | Drug: Dexamethasone<br>* Oral<br>Drug: Rovalpituzumab tesirine<br>* Intravenous<br>* Other names: SC16LD6.5;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with a High Grade (>= Grade 3) Protocol Specified TEAE | Number of participants with a high grade (≥ Grade 3) protocol specified Treatment-Emergent Adverse Events (TEAEs) during and after treatment with rovalpituzumab tesirine. Severity of TEAEs will be graded at each study visit according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03. | Approximately 32 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Participant Reported Outcome EORTC QLQC15-PAL | The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Palliative Cancer (EORTC QLQ-C15-PAL) is a 15-item self-report questionnaire composed of 4 multi-item scales (physical & emotional functioning, fatigue and pain) along with 6 individual items (nausea & vomiting, dyspnea, insomnia, appetite loss, constipation, and global quality of life). | Approximately 32 months | 
| Progression Free Survival (PFS) | PFS is based on independent review of radiographic assessment, defined as the time from randomization to documented disease progression or death from any cause, whichever occurs earlier. | Approximately 32 months | 
| Overall Survival (OS) | Overall Survival (OS) is defined as the time from the date of randomization to the date of death from any cause. | Approximately 32 months | 
| Objective response rate (ORR) | ORR is defined as the percentage of participants whose best overall response is either complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. | Approximately 32 months | 
| Change in EORTC QLQ-LC-13 | The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer (EORTC QLQ-LC 13) is a lung cancer specific module developed to assess lung cancer-associated symptoms and treatment-related side effects among lung cancer patients. | Approximately 32 months | 
| Duration of Objective Response (DOR) | DOR is defined as the time between the date of first response (CR or PR, whichever is recorded first) to the date of the first documented tumor progression (per RECIST version 1.1) or death due to any cause, whichever comes first. | Approximately 32 months | 
| Clinical Benefit Rate (CBR) | CBR is defined as the proportion of participants with an objective response or stable disease (CR+PR+SD) according to RECIST version 1.1. | Approximately 32 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Small Cell Lung Cancer, Relapsed Small Cell Lung Cancer, Remitting Small Cell Lung Cancer, Delta-like protein 3 (DLL3), DLL3 Expressing Small Cell Lung Cancer, Rovalpituzumab Tesirine