Study of Rovalpituzumab Tesirine (SC16LD6.5) for Third-Line and Later Treatment of Subjects With Relapsed or Refractory Delta-Like Protein 3-Expressing Small Cell Lung Cancer
Condition: Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Intervention: Rovalpituzumab tesirine
Intervention description: Rovalpituzumab tesirine is a DLL3 targeted antibody drug conjugate (ADC).
Intervention MeSH terms: Rovalpituzumab tesirine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 342.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: SCLC; Small Cell Lung Cancer; DLL#; Relapsed; Refractory

Summary:

      The purpose of this study is to determine the efficacy of rovalpituzumab tesirine as a
      third-line and later treatment for participants with relapsed or refractory delta-like
      protein 3 (DLL3) expressing small cell lung cancer (SCLC).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adult aged 18 years or older

          2. Histologically confirmed SCLC with documented disease progression after at least 2
             prior systemic regimens, including at least one platinum-based regimen

          3. DLL3-expressing SCLC based on central immunohistochemistry (IHC) assessment of banked
             or otherwise representative tumor tissue. Positive is defined as staining in ≥ 1% of
             tumor cells

          4. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
             version 1.1

          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 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

          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 (i.e., anti-PD-1, anti-PD-L1, or anti-CTLA-4): 4
                  weeks

               -  Other 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 6 months) or
             neurological disorder (e.g., seizure disorder active within 6 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 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 National Cancer Institute's Common Terminology
                  Criteria for Adverse Events [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 breastfeeding

          5. Systemic therapy with corticosteroids at >20 mg/day prednisone or equivalent within 1
             week prior to the first dose of study drug

          6. History of another invasive malignancy that has not been in remission for at least 3
             years. Exceptions to the 3 year limit include nonmelanoma skin cancer, curatively
             treated localized prostate cancer, and cervical cancer in situ on biopsy or squamous
             intraepithelial lesion on pap smear

          7. Prior exposure to a pyrrolobenzodiazepine (PBD)-based drug, 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