Efficacy and Safety of Rovalpituzumab Tesirine Compared with Topotecan as Second-Line Therapy in DLL3-High Small Cell Lung Cancer: Results from the Phase 3 TAHOE Study

Research output: Contribution to journalJournal articleResearchpeer-review

  • Fiona Blackhall
  • Kevin Jao
  • Laurent Greillier
  • Byoung Chul Cho
  • Konstantin Penkov
  • Noemi Reguart
  • Margarita Majem
  • Kristiaan Nackaerts
  • Konstantinos Syrigos
  • Karin Hansen
  • Wolfgang Schuette
  • Jeremy Cetnar
  • Federico Cappuzzo
  • Isamu Okamoto
  • Mustafa Erman
  • Terufumi Kato
  • Harry Groen
  • Zhaowen Sun
  • Yan Luo
  • Poonam Tanwani
  • Laura Caffrey
  • Philip Komarnitsky
  • Niels Reinmuth

INTRODUCTION: Delta-like protein 3 (DLL3), an atypical Notch ligand, is expressed in small cell lung cancer (SCLC) tumors but is not detectable in normal adult tissues. Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate containing a DLL3-targeting antibody tethered to a cytotoxic agent pyrrolobenzodiazepine via a protease-cleavable linker. Efficacy and safety of Rova-T compared with topotecan as second-line therapy in patients with SCLC expressing high levels of DLL3 (DLL3-high) was evaluated.

METHODS: TAHOE was an open-label, 2:1 randomized, phase 3 study comparing Rova-T with topotecan as second-line therapy in DLL3-high advanced or metastatic SCLC. Rova-T (0.3 mg/kg) was administered intravenously on Day 1 of a 42-day cycle for 2 cycles, with 2 additional cycles available to patients who met protocol-defined criteria for continued dosing. Topotecan (1.5 mg/m2) was administered intravenously on Days 1-5 of a 21-day cycle. The primary endpoint was overall survival (OS).

RESULTS: Patients randomized to Rova-T (n=296) and topotecan (n=148) were included in efficacy analyses. The median age was 64 years, and 77% had extensive disease at initial diagnosis. Median OS (95% CI) was 6.3 months (5.6-7.3) in the Rova-T arm and 8.6 months (7.7, 10.1) in the topotecan arm (hazard ratio, 1.46 [95% CI: 1.17-1.82]). An independent data monitoring committee recommended that enrollment be discontinued due to shorter OS observed with Rova-T compared with topotecan. Safety profiles for both drugs were consistent with previous reports.

CONCLUSIONS: Compared with topotecan, which is the current standard second-line chemotherapy, Rova-T showed an inferior OS and higher rates of serosal effusions, photosensitivity reaction, and peripheral edema in patients with SCLC. Significant unmet therapeutic need remains in this population.

Original languageEnglish
JournalJournal of Thoracic Oncology
Issue number9
Pages (from-to)1547-1558
Publication statusPublished - 2021

ID: 257374197