Clinical Trials

Inclusion Criteria:

• Subject or the subject's legally acceptable representative must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures and should be willing and able to comply with parameters as outlined in the protocol.
• Subject must be ≥ 18 years of age.
• Histologically or cytologically confirmed ED SCLC (extensive stage disease at initial diagnosis), with ongoing clinical benefit (SD, PR, or CR per RECIST v.1.1) following completion of 4 cycles of first-line platinum-based therapy (cisplatin or carboplatin in combination with etoposide or irinotecan).
• Subjects with a history of CNS metastases prior to the initiation of first-line platinum-based therapy must have received definitive local treatment and have documentation of stable or improved CNS disease status based on brain imaging within 28 days prior to randomization, off or on a stable dose of corticosteroids.
• Subject is eligible to be randomized at least 3 but no more than 9 weeks from Day 1 of the fourth cycle of first-line platinum-based chemotherapy.
• Availability of archived or representative tumor material for assessment of DLL3 expression.
• Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.
• Recovery to ≤ Grade 1 of any clinically significant toxicity (excluding alopecia) rior to randomization.
• Subject must have adequate bone marrow, renal and hepatic function as follows:
  • Absolute neutrophil count (ANC) ≥ 1,000/μL;
  • Platelet count ≥75,000/μL;
  • Hemoglobin ≥8.0 g/dL;
  • Serum total bilirubin ≤1.5 × upper limit of normal (ULN) or ≤3 × ULN for subjects with Gilbert's disease;
  • Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × ULN (≤5 × ULN if evidence of hepatic involvement by malignant disease);
  • Calculated creatinine clearance ≥30 mL/min by the modified Cockroft-Gault formula;
  • Albumin ≥ 3 g/dL.
• If female, subject must be either postmenopausal as 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 an FSH level > 40 IU/L; OR
  • Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy); OR
  • A Woman of Childbearing Potential (WOCBP) practicing at least one protocol specified method of birth control, starting at randomization through at least 6 months after the last dose of blinded investigational product;
  • If the male subject is sexually active, he must agree, from randomization through at least 6 months after the last dose of blinded investigational product, to practice the protocol specified contraception.
• Females of childbearing potential must have a negative serum pregnancy test result at Screening, and a negative urine pregnancy test at randomization. Females of non-childbearing potential (either postmenopausal or permanently surgically sterile) at Screening do not require pregnancy testing.

Exclusion Criteria:

• Any 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 anti-cancer therapy than that described in Inclusion Criteria 3 – 5 for SCLC.
• Any disease-directed radiotherapy (except PCI, palliative radiotherapy to a radiographically documented non-progressing lesion for symptom control, or preplanned radiotherapy for CNS metastases present prior to start of first-line therapy and non-progressing) after last dose of first-line chemotherapy.
• 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.
• Documented history of a cerebral vascular event, unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class III – IV heart failure (refer to Appendix F) within 6 months prior to randomization.
• Documented history of capillary leak syndrome.
• Grade 2 or higher pleural or pericardial effusion within 4 weeks of randomization or earlier history of recurrent Grade 2 or higher effusions with ongoing requirement for pericardiocentesis or thoracentesis.
• Serious infection within 2 weeks prior to randomization, including any Grade 3 or higher (per NCI CTCAE version 4.0)11 viral, bacterial, or fungal infection.
• Female subject who is pregnant, breastfeeding or is considering becoming pregnant during the study or for approximately 6 months after the last dose of blinded investigational product.
• Male subject who is considering fathering a child or donating sperm during the study or for approximately 6 months after the last dose of blinded investigational product.
• Systemic therapy with corticosteroids at > 10 mg/day prednisone or equivalent within 1 week prior to randomization.
• Subject has a history of active malignancies other than SCLC within the past 2 years prior to study entry, with the exception of in situ cancer which was curatively treated. 
• Any prior exposure to a pyrrolobenzodiazepine (PBD-based) or indolinobenzodiazepine-based drug, prior participation in a rovalpituzumab tesirine clinical trial, or known hypersensitivity or other contraindications to rovalpituzumab tesirine or excipient contained in the drug formulation.
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells.