Rovalpituzumab Tesirine in Delta-Like Protein 3-Expressing Advanced Solid Tumors

NCT ID: NCT02709889

Last Updated: 2020-10-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-23
• Study Completion Date: 2019-08-27

Brief Summary

The primary objective of this study is to assess the safety and tolerability of rovalpituzumab tesirine in subjects with specific delta-like protein 3-expressing advanced solid tumors.

Detailed Description

This is a multicenter, open-label study involving multiple specific advanced solid tumor types, consisting of a dose escalation part A followed by an expansion part B. Cancer subtypes will be studied in separate disease-specific cohorts in both Parts. Eight separate cohorts will enroll malignant melanoma, medullary thyroid cancer (MTC), glioblastoma, large cell neuroendocrine carcinoma (LCNEC), neuroendocrine prostate cancer (NEPC), high-grade gastroenteropancreatic neuroendocrine carcinoma (GEP NEC), other NEC, and solid tumors other than the above.

Conditions

Malignant Melanoma; Medullary Thyroid Cancer; Glioblastoma; Large-Cell Neuroendocrine Carcinoma; Neuroendocrine Prostate Cancer; High Grade Gastroenteropancreatic Neuroendocrine Carcinoma; Other Neuroendocrine Carcinoma; Other Solid Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rovalpituzumab Tesirine

Rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.

Group Type: EXPERIMENTAL

Rovalpituzumab tesirine

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Dexamethasone will be provided through a participant's local prescription by Investigator or other provider (i.e., dexamethasone will not be provided by the Sponsor).

Interventions

Rovalpituzumab tesirine

Intervention Type: DRUG

Dexamethasone

Dexamethasone will be provided through a participant's local prescription by Investigator or other provider (i.e., dexamethasone will not be provided by the Sponsor).

Intervention Type: DRUG

Other Intervention Names

SC16LD6.5

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed, unresectable advanced solid malignancy with documented disease progression after at least 1 prior systemic therapy
• Disease is relapsed/refractory to prior standard systemic therapy or for which standard or curative therapy does not exist or is not considered appropriate by the Investigator.
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Delta-like protein 3 (DLL3)-expressing malignancy based on central immunohistochemical (IHC) testing of representative baseline tumor tissue (archived tissue or on-study biopsy). Positive is defined as staining in ≥ 1% of tumor cells.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Minimum life expectancy of at least 12 weeks
• Subjects with a history of central nervous system (CNS) metastases must have documentation of stable or improved 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. Definitive treatment may include surgical resection, whole brain irradiation, and/or stereotactic radiation therapy. (Applicable to tumor types of non-CNS primary origin only)
• Recovery to Grade 1 of any clinically significant toxicity (excluding alopecia) prior to initiation of study drug administration
• Adequate hematologic and organ function as confirmed by laboratory values
• Last dose of any prior therapy administered by the following time intervals before the first dose of study drug:

1. Chemotherapy, small molecule inhibitors, radiation, and/or other investigational anticancer agents (excluding investigational monoclonal antibodies): 2 weeks.

2. Immune-checkpoint inhibitors (e.g., anti-programmed death protein 1 [PD-1], anti-programmed death-ligand 1 [PD-L1], or anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4]), monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or T-cell or other cell-based therapies: 4 weeks (2 weeks with documented disease progression).

• Females of childbearing potential must have a negative beta human chorionic gonadotropin (β-hCG) pregnancy test result within 7 days prior to the first dose of study drug. Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy.

Exclusion Criteria

• Any significant medical condition, including any suggested by screening laboratory findings that, in the opinion of the investigator or sponsor, may place the subject at undue risk from the study, including but not necessarily limited to uncontrolled hypertension and/or diabetes, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease requiring hospitalization within 3 months) or neurological disorder (e.g., seizure disorder active within 3 months).
• 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 (NYHA) Class III-IV within 6 months prior to their first dose of study drug.
• Recent or ongoing serious infection, including:

1. Any active grade 3 or higher (per National Cancer Institute Common Terminology Criteria for Adverse Events version [NCI CTCAE] 4.03) viral, bacterial, or fungal infection within 2 weeks of the first dose of the study drug. Routine antimicrobial prophylaxis is permitted.

2. Known seropositivity for or active infection by human immunodeficiency virus (HIV).

3. Active Hepatitis B (by surface antigen expression or polymerase chain reaction) or C (by polymerase chain reaction) infection or on hepatitis-related antiviral therapy within 6 months of first dose of study drug.

• Women who are pregnant or breastfeeding
• Systemic therapy with corticosteroids at >20 mg/day prednisone or equivalent within 1 week prior to the first dose of study drug
• History of another invasive malignancy that has not been in remission for at least 3 years. Exceptions to the 3year limit include non-melanoma skin cancer, curatively treated localized prostate cancer, ductal carcinoma in situ, and cervical cancer in situ on biopsy or squamous intraepithelial lesion on pap smear.
• Prior exposure to a pyrrolobenzodiazepine (PBD)-based drug, prior participation in a rovalpituzumab tesirine clinical trial, or known hypersensitivity to rovalpituzumab tesirine or excipient contained in the drug formulation, unless undergoing retreatment with rovalpituzumab tesirine in the context of this protocol

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

Locations

Banner MD Anderson Cancer Ctr /ID# 155424

Gilbert, Arizona, United States

Mayo Clinic - Scottsdale /ID# 155419

Scottsdale, Arizona, United States

University of California, Los Angeles /ID# 155429

Los Angeles, California, United States

Univ California, San Francisco /ID# 155409

San Francisco, California, United States

Cedars-Sinai Medical Center - West Hollywood /ID# 155428

West Hollywood, California, United States

Univ of Colorado Cancer Center /ID# 155415

Aurora, Colorado, United States

Sarah Cannon Research Institute at HealthONE - Denver /ID# 155420

Denver, Colorado, United States

University of Florida - Archer /ID# 155414

Gainesville, Florida, United States

Moffitt Cancer Center /ID# 170220

Tampa, Florida, United States

Emory University Hospital /ID# 155417

Atlanta, Georgia, United States

University of Kentucky Chandler Medical Center /ID# 155423

Lexington, Kentucky, United States

Johns Hopkins University /ID# 155412

Baltimore, Maryland, United States

Massachusetts General Hospital /ID# 155411

Boston, Massachusetts, United States

Dana-Farber Cancer Institute /ID# 171044

Boston, Massachusetts, United States

Mayo Clinic - Rochester /ID# 155416

Rochester, Minnesota, United States

Washington University-School of Medicine /ID# 155425

St Louis, Missouri, United States

Rutgers Cancer Institute of NJ /ID# 162010

New Brunswick, New Jersey, United States

University of New Mexico /ID# 205054

Albuquerque, New Mexico, United States

Roswell Park Comprehensive Cancer Center /ID# 162015

Buffalo, New York, United States

Weill Cornell Medical College /ID# 155418

New York, New York, United States

Duke University Medical Center /ID# 155421

Durham, North Carolina, United States

Univ Hosp Cleveland /ID# 155410

Cleveland, Ohio, United States

Oregon Health and Science University /ID# 162011

Portland, Oregon, United States

Greenville Hospital System /ID# 155427

Greenville, South Carolina, United States

Mary Crowley Cancer Research /ID# 162014

Dallas, Texas, United States

Texas Oncology - Forth Worth /ID# 162045

Fort Worth, Texas, United States

University of Texas MD Anderson Cancer Center /ID# 155413

Houston, Texas, United States

University of Utah /ID# 155426

Salt Lake City, Utah, United States

Virginia Cancer Specialists /ID# 162006

Fairfax, Virginia, United States

Northwest Cancer Specialists, P.C. /ID# 155431

Vancouver, Washington, United States

Countries

United States

References

Xie H, Kaye FJ, Isse K, Sun Y, Ramoth J, French DM, Flotte TJ, Luo Y, Saunders LR, Mansfield AS. Delta-Like Protein 3 Expression and Targeting in Merkel Cell Carcinoma. Oncologist. 2020 Sep;25(9):810-817. doi: 10.1634/theoncologist.2019-0877. Epub 2020 May 14.

Reference Type: DERIVED

PMID: 32372416 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

SCRX001-006

Identifier Type: -

Identifier Source: org_study_id