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

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

Study Overview

• Status: Terminated
• Conditions: Small Cell Lung Cancer
• Intervention / Treatment: Drug: Cisplatin; Drug: Etoposide; Drug: Rovalpituzumab Tesirine

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80010
      • University of Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers
  • Florida
    • Orlando, Florida, United States, 32804
      • Cancer Institute Of Florida
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • University Hospital of Cleveland
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology
    • San Antonio, Texas, United States, 78258
      • Texas Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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
Overall Survival (OS)		4 years
Duration of response (DOR)		4 years
Best overall response rate		4 years
Clinical Benefit Rate (CBR)		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

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Actual): May 31, 2019
• Study Completion (Actual): May 31, 2019

Study Registration Dates

• First Submitted: June 27, 2016
• First Submitted That Met QC Criteria: June 28, 2016
• First Posted (Estimate): June 30, 2016

Study Record Updates

• Last Update Posted (Actual): March 12, 2020
• Last Update Submitted That Met QC Criteria: March 11, 2020
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Etoposide; Cisplatin
• Other Study ID Numbers: SCRX001-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO