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

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

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).

Study Overview

• Status: Withdrawn
• Conditions: Small Cell Lung Cancer
• Intervention / Treatment: Drug: Rovalpituzumab tesirine; Drug: Dexamethasone

• Study Type: Interventional
• Phase: Phase 3

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Coffs Harbour, New South Wales, Australia, 2450
      • Coffs Harbour Health Campus /ID# 200642
    • Tweed Heads, New South Wales, Australia, 2485
      • The Tweed Hospital /ID# 200646
  • Queensland
    • Douglas, Queensland, Australia, 4814
      • The Townsville Hospital /ID# 200640
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital /ID# 200639
    • Wodonga, Victoria, Australia, 3690
      • Border Medical /ID# 200645
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Perron Institute for Neurological and Translational Science /ID# 200644
• Brazil
  • Rio de Janeiro, Brazil, 20231-050
    • Inca /Id# 202594
  • Rio de Janeiro, Brazil, 22793-080
    • Instituto COI de Educacao e Pe /ID# 200499
  • Sao Paulo, Brazil, 01509-000
    • Fundacao Antonio Prudente /ID# 200218
  • Sao Paulo, Brazil, 14784-400
    • Hospital de Cancer de Barretos /ID# 200104
  • Bahia
    • Salvador, Bahia, Brazil, 40170-110
      • Bahia Oncology Center - NOB /ID# 201272
  • Rio Grande Do Sul
    • Ijuí, Rio Grande Do Sul, Brazil, 98700-000
      • Associação Hospital de Caridade Ijuí - Centro de Tratamento de Cancer - CACON /ID# 200496
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
      • Hospital Sao Lucas da PUCRS /ID# 201258
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 01246-000
      • Icesp /Id# 201036
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre /ID# 171561
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • QE II Health Sciences Centre /ID# 171569
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre /ID# 171567
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital /ID# 200682
• Germany
  • Berlin, Germany, 13353
    • Charite Universitatsmedizin B- /ID# 170079
  • Gauting, Germany, 82131
    • Asklepios Fachkliniken M. Gaut /ID# 170081
  • Heidelberg, Germany, 69126
    • Thoraxklinik Heidelberg gGmbH /ID# 170078
  • Kassel, Germany, 34125
    • Klinikum Kassel - Onkologie /ID# 170083
  • Muenster, Germany, 48149
    • Universitatsklinikum Munster /ID# 170087
  • Oldenburg, Germany, 26121
    • Pius Hospital Oldenburg /ID# 170080
  • Niedersachsen
    • Georgsmarienhütte, Niedersachsen, Germany, 49124
      • Franziskus-Hospital Harderberg /ID# 201145
• Sweden
  • Gavle, Sweden, 801 88
    • Gavle Hospital /ID# 171253
  • Linkoping, Sweden, 58185
    • University Hospital Linkoping /ID# 201666
  • Stockholm, Sweden, SE-17176
    • Karolinska University Hospital /ID# 201967
  • Umeå, Sweden, 90185
    • Norrlands Universitetssjukhus /ID# 171250
  • Uppsala Lan
    • Uppsala, Uppsala Lan, Sweden, 751 85
      • Akademiska Sjukhuset /ID# 171248
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • Christie NHS Foundation Trust /ID# 201149
  • Preston, United Kingdom, PR2 9HT
    • Royal Preston Hospital /ID# 201146
  • England
    • Leicester, England, United Kingdom, LE1 5WW
      • Leicester Royal Infirmary /ID# 201154
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224-5665
      • Ironwood Cancer & Res Ctr /ID# 171335
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic - Scottsdale /ID# 171359
  • California
    • Fresno, California, United States, 93703
      • VA Central California Health C /ID# 170951
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical /ID# 171377
    • Orange, California, United States, 92868-3201
      • UC Irvine Health /ID# 171343
    • Roseville, California, United States, 95661-3027
      • Kaiser Permanente - Roseville /ID# 200779
    • Santa Clara, California, United States, 95051-5173
      • Kaiser Permanente-Santa Clara /ID# 203024
    • Vallejo, California, United States, 94589-2441
      • Kaiser Permanente Medical Ctr-Vallejo /ID# 169758
    • Walnut Creek, California, United States, 94596
      • Kaiser Permanente- Walnut Creek /ID# 201305
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Univ of Colorado Cancer Center /ID# 200810
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Boca Raton Regional Hospital /ID# 200168
    • Deerfield Beach, Florida, United States, 33442
      • UMHC/Sylvester Comprehensive /ID# 171462
    • Miami, Florida, United States, 33140
      • Mount Sinai Comp Cancer Ctr /ID# 169759
  • Illinois
    • Peoria, Illinois, United States, 61615
      • Illinois Cancer Care, PC /ID# 171310
  • Kentucky
    • Lexington, Kentucky, United States, 40503-1463
      • Baptist Health /ID# 171379
    • Louisville, Kentucky, United States, 40202-3700
      • Norton Cancer Institute /ID# 200827
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Cancer Center Clinic /ID# 171376
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Sandra Malcolm Berman Cncr Ins /ID# 171346
  • Minnesota
    • Duluth, Minnesota, United States, 55802
      • St. Luke's University Hospital /ID# 171374
  • New Jersey
    • Westwood, New Jersey, United States, 07675
      • Valley Hospital - Westwood, NJ /ID# 171357
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157-0001
      • Wake Forest Baptist Medical Center /ID# 169799
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Comp /ID# 171352
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's Hematology Oncology /ID# 171378
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology PLLC: Sarah /ID# 171380
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt Ingram Henry Cancer /ID# 171356
  • Virginia
    • Arlington, Virginia, United States, 22031
      • VCS, Virginia Cancer Specialis /ID# 169760
  • Washington
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and O /ID# 169797

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:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rovalpituzumab tesirine + dexamethasone; 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: Rovalpituzumab tesirine; Intravenous; Other Names: SC16LD6.5; Drug: Dexamethasone; Oral

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2018
• Primary Completion (Actual): December 20, 2018
• Study Completion (Actual): December 20, 2018

Study Registration Dates

• First Submitted: November 3, 2017
• First Submitted That Met QC Criteria: November 3, 2017
• First Posted (Actual): November 7, 2017

Study Record Updates

• Last Update Posted (Actual): December 26, 2018
• Last Update Submitted That Met QC Criteria: December 21, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Cancer; Relapsed Small Cell Lung Cancer; Small Cell Lung Cancer; Delta-like protein 3 (DLL3); Remitting Small Cell Lung Cancer; DLL3 Expressing Small Cell Lung Cancer; Rovalpituzumab Tesirine
• 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; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: M16-292; 2017-003173-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No