MC# 16-29 - An Open-Label Study of Rovalpituzumab Tesirine in Subjects with Delta-Like Protein 3-Expressing Advanced Solid Tumors

  • Agent(s): Rovalpituzumab Tesirine
  • Disease Type(s): Melanoma, Prostate, Glioblastoma, Thyroid, Neuroendocrine
  • Phase(s): I
  • Drug Classification(s): Targeted Therapy, Immunotherapy, Monoclonal Antibody
  • Molecular Target(s): DLL3

Mechanism of Action

Rovalpituzumab tesirine is a Delta-like protein 3 (DLL3) targeted antibody-drug conjugate (ADC) consisting of a humanized DLL3-specific IgG1 monoclonal antibody.  DLL3 is an inhibitory ligand of the Notch receptor family.  Binding of the ADC to DLL3 on target-expressing cells is followed by internalization of the ADC-DLL3 complex and leads to cellular cytotoxicity.


In this study, the sponsor and investigators want to learn:

  • How much Rovalpituzumab Tesirine can be given with an acceptable level of side effects 
  • How much Rovalpituzumab Tesirine is absorbed into the blood and how fast it is removed
  • The effects of Rovalpituzumab Tesirine
  • If research tests can predict who will benefit from Rovalpituzumab Tesirine
Inclusion Criteria
  • Ability to provide written informed consent.
  • Histologically confirmed, unresectable advanced solid malignancy other than small cell lung cancer.
  • Measurable disease, defined as at least 1 tumor lesion ≥10 mm in the longest diameter or a lymph node ≥15 mm in short-axis measurement assessed by CT scan (RECIST v1.1).
  • Disease refractory to standard therapy or for which standard or curative therapy does not exist or is not considered appropriate.
  • 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. See Appendix 12.3 for conversion of performance status using Karnofsky scales, if applicable.
  • 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.
  • Satisfactory laboratory parameters:
    • Absolute neutrophil count (ANC) ≥1,500/mL.
    • Platelet count ≥75,000/mL.
    • Hemoglobin ≥8.0 g/dL.
    • Total bilirubin ≤1.5X upper limit of normal (ULN) or ≤3X ULN for subjects with Gilbert’s disease.
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5X ULN (≤5X ULN if evidence of hepatic involvement by malignant disease).
    • Creatinine ≤1.5X ULN or estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2.
  • 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).
  • Females of childbearing potential must have a negative serum or urine 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.
  • Females of childbearing potential and males who have partners of childbearing potential must agree to use an effective contraception method during the study and for 6 months following the last dose of study drug. Effective birth control includes (a) intrauterine device plus 1 barrier method; or (b) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm).
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:
    • 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.
  • 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.


  • Dallas, TX - Mary Crowley Cancer Research - Medical City
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Re: MC# 16-29