A Study of Rovalpituzumab Tesirine (SC16LD6.5) in the Frontline Treatment of Patients With Extensive Stage Small Cell Lung Cancer
Phase 1
Terminated
- Conditions
- Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT02819999
- Lead Sponsor
- AbbVie
- Brief Summary
The purpose of the study is to test the effect of rovalpituzumab tesirine in the frontline treatment of small cell lung cancer (SCLC).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 28
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Rovalpituzumab Tesirine followed by Cisplatin, Etoposide Cisplatin Rovalpituzumab Tesirine 0.3 mg/kg IV infusion followed by Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion Rovalpituzumab Tesirine followed by Cisplatin, Etoposide Etoposide Rovalpituzumab Tesirine 0.3 mg/kg IV infusion followed by Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion Rovalpituzumab Tesirine with Cisplatin, Etoposide Cisplatin Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion and Rovalpituzumab Tesirine 0.1 mg/kg IV infusion Rovalpituzumab Tesirine with Cisplatin, Etoposide Etoposide Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion and Rovalpituzumab Tesirine 0.1 mg/kg IV infusion Rovalpituzumab Tesirine following Cisplatin, Etoposide Cisplatin Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion followed by Rovalpituzumab Tesirine 0.3 mg/kg IV infusion Rovalpituzumab Tesirine following Cisplatin, Etoposide Etoposide Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion followed by Rovalpituzumab Tesirine 0.3 mg/kg IV infusion Rovalpituzumab Tesirine Rovalpituzumab Tesirine Rovalpituzumab Tesirine 0.3 mg/kg IV infusion Rovalpituzumab Tesirine followed by Cisplatin, Etoposide Rovalpituzumab Tesirine Rovalpituzumab Tesirine 0.3 mg/kg IV infusion followed by Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion Rovalpituzumab Tesirine with Cisplatin, Etoposide Rovalpituzumab Tesirine Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion and Rovalpituzumab Tesirine 0.1 mg/kg IV infusion Rovalpituzumab Tesirine following Cisplatin, Etoposide Rovalpituzumab Tesirine Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion followed by Rovalpituzumab Tesirine 0.3 mg/kg IV infusion
- Primary Outcome Measures
Name Time Method 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) within 21 days after first dose of rovalpituzumab tesirine For Phase 1a
Treatment emergent adverse events (TEAEs) through 30 days after last dose of study treatment For Phase 1a
Incidence of subjects with CTCAE Grade >2 laboratory abnormalities through 30 days after last dose of study treatment For Phase 1a
Progression-Free Survival (PFS) 4 years For Phase 1b
- Secondary Outcome Measures
Name Time Method 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 4 years For Phase 1b
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
Trial Locations
- Locations (10)
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
University Hospital of Cleveland
🇺🇸Cleveland, Ohio, United States
Rocky Mountain Cancer Centers
🇺🇸Denver, Colorado, United States
Cancer Institute of Florida
🇺🇸Orlando, Florida, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Oncology Hematology Care
🇺🇸Cincinnati, Ohio, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Texas Oncology
🇺🇸San Antonio, Texas, United States
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States