A Study of Rovalpituzumab Tesirine (SC16LD6.5) in the Frontline Treatment of Patients With Extensive Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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The purpose of the study is to test the effect of rovalpituzumab tesirine in the frontline treatment of small cell lung cancer (SCLC).

Official Title
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A Study of Rovalpituzumab Tesirine (SC16LD6.5) in the Frontline Treatment of Patients With Extensive Stage Small Cell Lung Cancer

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Rovalpituzumab Tesirine
* Drug: Cisplatin
* Drug: Etoposide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years with histologically- or cytologically-confirmed, extensive-stage, chemotherapy-naïve SCLC DLL3-expressing SCLC based on central immunohistochemistry (IHC) assessment. Positive is defined as staining in ≥75% of tumor cells. Eastern Cooperative Oncology Group performance status of 0 or 1. Minimum life expectancy of at least 12 weeks. Recovery to Grade 1 of any clinically significant toxicity (excluding alopecia) prior to initiation of study drug. Satisfactory laboratory parameters within defined parameters (ANC, platelet count, Hb, total bilirubin, ALT, AST and GFR) Subjects with a history of CNS metastases must have completed definitive treatment prior to first dose of study treatment, off or on a stable dose of corticosteroids Use of effective contraception method during and for 1 year following study drug dosing if female of childbearing potential or sexually active male Exclusion Criteria: Prior systemic chemotherapy, small molecule inhibitors, immune checkpoint inhibitors, other monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, T-cell or other cell-based or biologic therapies, or any other anticancer therapy for the treatment of (limited or extensive) SCLC. Any significant medical condition, that, in the opinion of the investigator or sponsor, may place the subject at undue risk from the study. Documented history of a cerebral vascular, unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class III-IV within 6 months prior to their first dose of study drug. Recent or ongoing serious infection. Women who are pregnant or breastfeeding. History of another invasive malignancy that has not been in remission for at least 3 years. Exceptions: nonmelanoma skin cancer, curatively treated localized prostate cancer, and cervical cancer in situ on biopsy or squamous intraepithelial lesion on PAP smear. Prior exposure to a pyrrolobenzodiazepine (PBD)-based drug, 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rovalpituzumab Tesirine<br>Rovalpituzumab Tesirine 0.3 mg/kg IV infusion | Drug: Rovalpituzumab Tesirine<br>* Rovalpituzumab tesirine is a DLL3 targeted antibody drug conjugate (ADC).<br>* Other names: SC16LD6.5;|
| Experimental: Rovalpituzumab Tesirine followed by Cisplatin, Etoposide<br>Rovalpituzumab Tesirine 0.3 mg/kg IV infusion followed by Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion | Drug: Rovalpituzumab Tesirine<br>* Rovalpituzumab tesirine is a DLL3 targeted antibody drug conjugate (ADC).<br>* Other names: SC16LD6.5;Drug: Cisplatin<br> <br> Drug: Etoposide<br> <br> |
| Experimental: Rovalpituzumab Tesirine with Cisplatin, Etoposide<br>Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion and Rovalpituzumab Tesirine 0.1 mg/kg IV infusion | Drug: Rovalpituzumab Tesirine<br>* Rovalpituzumab tesirine is a DLL3 targeted antibody drug conjugate (ADC).<br>* Other names: SC16LD6.5;Drug: Cisplatin<br> <br> Drug: Etoposide<br> <br> |
| Experimental: Rovalpituzumab Tesirine following Cisplatin, Etoposide<br>Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion followed by Rovalpituzumab Tesirine 0.3 mg/kg IV infusion | Drug: Rovalpituzumab Tesirine<br>* Rovalpituzumab tesirine is a DLL3 targeted antibody drug conjugate (ADC).<br>* Other names: SC16LD6.5;Drug: Cisplatin<br> <br> Drug: Etoposide<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicities (DLT) of rovalpituzumab tesirine when administered as monotherapy, in series or in combination with frontline chemotherapy to subjects with DLL3 expressing extensive-stage small cell lung cancer (SCLC) | For Phase 1a | within 21 days after first dose of rovalpituzumab tesirine | 
| Treatment emergent adverse events (TEAEs) | For Phase 1a | through 30 days after last dose of study treatment | 
| Incidence of subjects with CTCAE Grade >2 laboratory abnormalities | For Phase 1a | through 30 days after last dose of study treatment | 
| Progression-Free Survival (PFS) | For Phase 1b | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best overall response rate |  | 4 years | 
| Duration of response (DOR) |  | 4 years | 
| Clinical Benefit Rate (CBR) |  | 4 years | 
| Overall Survival (OS) |  | 4 years | 
| Incidence of anti-therapeutic antibodies (ATAs) against rovalpituzumab tesirine |  | 4 years | 
| Progression-free survival (Phase 1a) |  | 4 years | 
| Pharmacokinetic parameters: Cmax (Maximum plasma concentration observed ) |  | 4 years | 
| Pharmacokinetic parameters: AUC0-tau (Area under the plasma concentration-time curve within a dosing interval) |  | 4 years | 
| Pharmacokinetic parameters: AUC0-∞ (Area under the curve from time 0 extrapolated to infinity) |  | 4 years | 
| Pharmacokinetic parameters: Tmax (Time of Cmax) |  | 4 years | 
| Pharmacokinetic parameters: Ctrough (Observed plasma concentrations at trough) |  | 4 years | 
| Pharmacokinetic parameters: T1/2 (Terminal half-life) |  | 4 years | 
| Pharmacokinetic parameters: CL (Clearance) |  | 4 years | 
| Pharmacokinetic parameters: Vss (Volume of distribution at steady state) |  | 4 years | 
| Incidence of TEAEs | For Phase 1b | 4 years | 
| Changes in vital signs (Heart Rate) |  | 4 years | 
| Changes in vital signs (Blood pressure) |  | 4 years | 
| Changes in vital signs (Temperature) |  | 4 years | 
| Changes in vital signs (Weight) |  | 4 years | 
| Changes in vital signs (Respirations) |  | 4 years | 
| Eastern Cooperative Oncology Group (ECOG) score |  | 4 years |