Inclusion Criteria:

• Ability to provide written informed consent.
• Histologically confirmed, unresectable advanced solid malignancy other than SCLC.
  • Note: Subjects with prostate cancer must also meet the additional prostate-specific criteria in Appendix 13.7.
• Measurable disease, defined as at least one tumor lesion ≥10 mm in the longest diameter, or a lymph node ≥15 mm in short-axis measurement, assessed by computerized tomography (CT) scan (by RECIST v1.1).
• Disease refractory to standard therapy or for which standard or curative therapy does not exist or is not considered appropriate by the Investigator.
• 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. Refer to Appendix 13.3 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/L.
  • Platelet count ≥75,000/L.
  • Hemoglobin ≥8.0 g/dL.
  • Total bilirubin ≤1.5× upper limit of normal (ULN) or ≤× ULN for subjects with Gilbert’s disease.
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5× ULN (≤× ULN if evidence of hepatic involvement by malignant disease).
  • Creatinine ≤.5× ULN or estimated glomerular filtration rate (eGFR) ≥0 mL/min/1.73m2.
  • Serum albumin ≥3.0 g/dL
• 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).
• If female, subject must be either postmenopausal defined as:
  • Age >55 years with no menses for 12 or more months without an alternative medical cause;
  • Age ≤55 years with no menses for 12 or more months without an alternative medical cause AND follicle stimulating hormone (FSH) level >40 IU/L;
  • Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy hysterectomy);
  • A Woman of Childbearing Potential (WOCBP) practicing at least one protocol specified method of birth control (Section 4.3.1) starting at Study Day 1 through at least 6 months after the last dose of study drug.
• If the male subject is sexually active, he must agree, from Study Day 1 through at least 6 months after the last dose of study drug, to practice the protocol specified contraception.
• Females of childbearing potential must have a negative serum pregnancy test result at screening and a pre-dose negative urine pregnancy test on Cycle 1 Day 1 (C1D1). Females of non-childbearing potential (either postmenopausal or permanently surgically sterile as defined in Section 4.3) at screening do not require pregnancy testing.

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 (refer to Appendix 13.5) within 6 months prior to their first dose of study drug.
• Recent or ongoing serious infection, including:
  • Any active Grade 3 or higher (according to 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 Hepatitis C (by polymerase chain reaction) infection or on hepatitis-related antiviral therapy within 6 months of first dose of study drug.
• Female subject who is pregnant, breastfeeding, or is considering becoming pregnant during the study or for approximately 6 months after the last dose of study drugs.
• Male subject who is considering fathering a child or donating sperm during the study for approximately 6 months after the last dose of study drugs.
• 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 3-year 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.