Protocol Summary

Protocol No.: 15092

Sponsor Protocol No.: SCRX001-006

Study Title
An Open-Label Study of Rovalpituzumab Tesirine in Subjects with Delta-Like Protein 3-Expressing Advanced Solid Tumors

Principal Investigator(s)
Kaye, Frederic

Objective
This study is being conducted to assess the safety and tolerability of rovalpituzumab tesirine in subjects with specific delta-like protein 3-expressing advanced solid tumors.

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 (GEP), neuroendocrine carcinoma (NEC), other NEC, and solid tumors other than the above.

Phase: Phase I/II

Age Group: Adult

Scope: National

Treatment
Experimental: Rovalpituzumab tesirine
Rovalpituzumab tesirine 0.2-0.4 mg/kg will be administered intravenously on Day 1 of each 6-week cycle.

Detailed Eligibility
INCLUSION CRITERIA:
1. Ages 18 years old and older
2. Histologically confirmed, unresectable advanced solid malignancy with documented disease progression after at least 1 prior systemic therapy
3. Measurable disease as defined by RECIST 1.1
4. 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.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
6. Minimum life expectancy of at least 12 weeks
7. 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)
8. Recovery to Grade 1 of any clinically significant toxicity (excluding alopecia) prior to initiation of study drug administration
9. Adequate hematologic and organ function as confirmed by laboratory values
10. Last dose of any prior therapy administered by the following time intervals before the first dose of study drug:
- Chemotherapy, small molecule inhibitors, radiation, and/or other investigational anticancer agents (excluding investigational monoclonal antibodies): 2 weeks.
- Immune-checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1, or anti-CTLA-4), monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or T-cell or other cell-based therapies: 4 weeks (2 weeks with documented disease progression).
11. 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:
1. 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).
2. 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 (see Appendix 12.4) within 6 months prior to their first dose of study drug.
3. Recent or ongoing serious infection, including:
- Any active grade 3 or higher (per NCI CTCAE version 4.03) viral, bacterial, or fungal infection within 2 weeks of the first dose of the study drug. Routine antimicrobial prophylaxis is permitted.
- Known seropositivity for or active infection by human immunodeficiency virus (HIV).
- 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.
4. Women who are pregnant or breastfeeding
5. Systemic therapy with corticosteroids at >20 mg/day prednisone or equivalent within 1 week prior to the first dose of study drug

** Contact Study Team for complete eligibility details

Applicable Disease Sites
Bladder Cancer
Brain and Nervous System
Breast Cancer
Colon Cancer
Gastrointestinal Cancer
Gynecologic Cancer
Head & Neck Cancer
Kidney Cancer (Renal Cell)
Liver Cancer
Lung Cancer
Melanoma
Ovarian Cancer
Pancreatic Cancer
Prostate Cancer
Sarcoma
Skin Cancer
Urologic Cancer

Participating Institutions
UF Gainesville

Contact
Allison Trainor
Phone: 352-265-0680
Phone Extension: 50703
Email: awickham@ufl.edu

More Information:
View study listing on ClinicialTrials.gov
http://www.clinicaltrials.gov/ct2/show/
NCT02709889