Strategic considerations

The purpose of the study is to test the effect of rovalpituzumab tesirine in the frontline treatment of small cell lung cancer (SCLC).

Inclusion Criteria:

• Age ≥ 18 years with histologically- or cytologically-confirmed, extensive-stage, chemotherapy-naïve SCLC
• DLL3-expressing SCLC based on central immunohistochemistry (IHC) assessment. Positive is defined as staining in ≥75% of tumor cells.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Minimum life expectancy of at least 12 weeks.
• Recovery to Grade 1 of any clinically significant toxicity (excluding alopecia) prior to initiation of study drug.
• Satisfactory laboratory parameters within defined parameters (ANC, platelet count, Hb, total bilirubin, ALT, AST and GFR)
• Subjects with a history of CNS metastases must have completed definitive treatment prior to first dose of study treatment, off or on a stable dose of corticosteroids
• Use of effective contraception method during and for 1 year following study drug dosing if female of childbearing potential or sexually active male

Exclusion Criteria:

• Prior systemic chemotherapy, small molecule inhibitors, immune checkpoint inhibitors, other monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, T-cell or other cell-based or biologic therapies, or any other anticancer therapy for the treatment of (limited or extensive) SCLC.
• Any significant medical condition, that, in the opinion of the investigator or sponsor, may place the subject at undue risk from the study.
• Documented history of a cerebral vascular, 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.
• Women who are pregnant or breastfeeding.
• History of another invasive malignancy that has not been in remission for at least 3 years. Exceptions: nonmelanoma skin cancer, curatively treated localized prostate cancer, and cervical cancer in situ on biopsy or squamous intraepithelial lesion on PAP smear.
• Prior exposure to a pyrrolobenzodiazepine (PBD)-based drug, or known hypersensitivity to rovalpituzumab tesirine or excipient contained in the drug formulation