Clinical Trial 18837

Cancer Type: Multiple
Interventions:Dexamethasone; Rovalpituzumab Tesirine

Study Type: Treatment
Phase of Study: Phase I/II
Investigators:

  • Jonathan Strosberg

Overview

Study Title

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

Summary

The purpose of this study is to test an investigational drug called rovalpituzumab tesirine (SC16LD6.5, also known as the "study drug") for the possible study treatment of cancer. This study is being conducted to test whether or not this study drug is effective against various types of cancer that express a particular protein, delta-like protein 3 (DLL3).

Objective

Primary: To assess the safety and tolerability of rovalpituzumab tesirine in subjects with specific delta-like protein 3-expressing advanced solid tumors. Secondary: To explore the antitumor activity of rovalpituzumab tesirine in subjects with specific delta-like protein 3-expressing advanced solid tumors. To study the pharmacokinetics of and incidence of anti-therapeutic antibodies (ATA) against rovalpituzumab tesirine in subjects with specific delta-like protein 3-expressing advanced solid tumors. Exploratory: To explore the expression of DLL3 in specific delta-like protein 3-expressing advanced solid tumors and its relationship to clinical outcome during treatment with rovalpituzumab tesirine. To explore the effect of rovalpituzumab tesirine on disease biomarkers and pharmacodynamics.

Inclusion Criteria

  • Histologically confirmed, unresectable advanced solid malignancy with documented disease progression after at least 1 prior systemic therapy
  • Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • 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
  • Potential participants 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: a.) Chemotherapy, small molecule inhibitors, radiation, and/or other investigational anticancer agents (excluding investigational monoclonal antibodies): 2 weeks. b.) 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 beta human chorionic gonadotropin (β-hCG) pregnancy test result within 7 days prior to the first dose of study drug.

  • 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 participant 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: a.) 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. b.) Known seropositivity for or active infection by human immunodeficiency virus (HIV). c.) 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