Study Comparing Rovalpituzumab Tesirine Versus Topotecan in Subjects With Advanced or Metastatic Small Cell Lung Cancer With High Levels of Delta-like Protein 3 (DLL3) and Who Have First Disease Progression During or Following Front-line Platinum-based Chemotherapy (TAHOE)
Condition: Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma; Disease Progression
Intervention: Rovalpituzumab tesirine; Topotecan; Dexamethasone
Intervention description: Powder for solution for infusion in vials.; Powder or solution for infusion in vials. Topotecan is commercially available as both a powder and solution for infusion. Availability will vary by region.; Oral tablet.
Intervention MeSH terms: Dexamethasone; Topotecan; Rovalpituzumab tesirine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 444.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Small cell lung cancer (SCLC); Delta-like protein 3 (DLL3); rovalpituzumab tesirine; topotecan; metastatic

Summary:

      The purpose of this randomized, open-label, 2-arm, phase 3 study is to assess the efficacy,
      safety and tolerability of rovalpituzumab tesirine versus topotecan in participants with
      advanced or metastatic SCLC with high levels of DLL3, who have first disease progression
      during or following front-line platinum-based chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant must have histologically or cytologically confirmed advanced or metastatic
             Small Cell Lung Cancer (SCLC) with documented first disease progression during or
             following front-line platinum-based systemic regimen

          -  Tumor must have high Delta-like protein 3 (DLL3) expression defined as having ≥ 75%
             tumor cells staining positive according to the VENTANA DLL3 (SP347) IHC Assay.

          -  Participant must have measurable disease, as defined per Response Evaluation Criteria
             in Solid Tumors (RECIST) version 1.1.

          -  Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status
             of 0 or 1.

          -  Participant must have recovery to Grade 0 or 1 of any clinically significant toxicity
             (excluding alopecia) prior to initiation of study drug administration.

        Exclusion Criteria:

          -  Participant has a 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 Class (NYHA) III - IV within 6 months prior
             to their first dose of study drug.

          -  Participant has known leptomeningeal metastases.

          -  Participant has received more than one prior systemic therapy regimen for SCLC.

          -  Participant had a serious infection within 2 weeks prior to randomization, including
             any Grade 3 or higher viral, bacterial, or fungal infection.

          -  Participant 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.

          -  Participant had prior exposure to topotecan, irinotecan or any other topoisomerase I
             inhibitors.