Elsevier

Journal of Thoracic Oncology

Volume 16, Issue 9, September 2021, Pages 1547-1558
Journal of Thoracic Oncology

Original Article
Small Cell Lung Cancer
Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-High SCLC: Results From the Phase 3 TAHOE Study

https://doi.org/10.1016/j.jtho.2021.02.009Get rights and content
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open access

Abstract

Introduction

DLL3, an atypical Notch ligand, is expressed in 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 by means of a protease-cleavable linker. The 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

The TAHOE study was an open-label, two-to-one 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 two cycles, with two additional cycles available to patients who met protocol-defined criteria for continued dosing. Topotecan (1.5 mg/m2) was administered intravenously on days 1 to 5 of a 21-day cycle. The primary end point was overall survival (OS).

Results

Patients randomized to Rova-T (n = 296) and topotecan (n = 148) were included in the efficacy analyses. The median age was 64 years, and 77% had the extensive disease at initial diagnosis. The median OS (95% confidence interval) 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% confidence interval: 1.17–1.82]). An independent data monitoring committee recommended that enrollment be discontinued because of the 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 exhibited an inferior OS and higher rates of serosal effusions, photosensitivity reaction, and peripheral edema in patients with SCLC. A considerable unmet therapeutic need remains in this population.

Keywords

Small cell lung cancer
Rovalpituzumab tesirine
Delta-like protein 3
Topotecan

Cited by (0)

Disclosures: Dr. Blackhall reports participating on advisory boards of AbbVie, AstraZeneca, Roche, Boehringer Ingelheim, Novartis, Pfizer, Celgene, Regeneron, and Amgen. Dr. Jao reports serving on the advisory boards of AbbVie, Roche, AstraZeneca, and Merck. Dr. Greillier reports participating on the advisory boards of AbbVie, AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, and Roche. Dr. Cho reports receiving research funding from Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, Merck Sharp & Dohme, AbbVie, Medpacto, GIInnovation, Eli Lilly, Blueprint Medicines, and Interpark Bio Convergence Corp.; serves as a consultant for Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, Merck Sharp & Dohme, Janssen, Medpacto, and Blueprint Medicines; has stock ownership at TheraCanVac Inc., Gencurix Inc., Bridgebio therapeutics, KANAPH Therapeutic Inc., Cyrus therapeutics, and Interpark Bio Convergence Corp.; serves on the scientific advisory boards of KANAPH Therapeutics Inc., Brigebio Therapeutics, Cyrus Therapeutics, and Guardant Health; serves as a member of the board of directors of Gencurix Inc. and Interpark Bio Convergence Corp; received royalty from Champions Oncology; and is the founder of DAAN Biotherapeutics. Dr. Penkov reports receiving honoraria from AbbVie, AstraZeneca, GlaxoSmithKline, H3B, Janssen, Merck Sharp & Dohme, Mylan, Nektar, Pfizer, Polyphor, Prestige, Regeneron, Roche, Takeda, and Tanvex. Dr. Reguart reports receiving research grants from Pfizer and Novartis; and served in the consulting, advisory, and speaker activities for Merck, Roche, AstraZeneca, Pfizer, Amgen, Novartis, Eli Lilly, Takeda, and Boehringer Ingelheim. Dr. Majem reports receiving grants and personal fees from Bristol-Myers Squibb; personal fees and nonfinancial support from Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca, and Roche; personal fees from Kyowa Kyrin; and personal fees from Pierre Fabre and Novartis outside the submitted work. Dr. Nackaerts reports participating in advisory boards for AbbVie, Boehringer Ingelheim, Novartis, Pfizer, and Roche. Dr. Schuette reports receiving sponsorship from and served a consulting or advisory role with Roche, Eli Lilly, Amgen, and Merck. Dr. Cappuzzo reports serving in an advisory role for and received honoraria from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Eli Lilly, Bayer, Pfizer, Roche, Pharmamar, and Takeda. Dr. Okamoto reports receiving grants from AbbVie, Astellas Pharma, and Boehringer Ingelheim during the conduct of the study; and grants and personal fees from AstraZeneca, Bristol-Myers Squibb, Chugai Pharma, Eli Lilly Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, Merck Sharp & Dohme Oncology, and Novartis; and personal fees from Pfizer outside the submitted work. Dr. Erman reports receiving honoraria and consulting fees from Pfizer, AstraZeneca, Novartis, Merck Sharp & Dohme, Bristol-Myers Squibb, Boehringer Ingelheim, Roche, and Nobel. Dr. Langer reports receiving a research grant from AbbVie, and participated in the advisory boards of Merck, Roche, AstraZeneca, and Pfizer. Dr. Kato reports receiving grants from AbbVie during the conduct of the study; grants and personal fees from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Chugai, Eli Lilly, Merck Biopharma, Merck Sharp & Dohme, Novartis, Ono, Pfizer, and Taiho; received personal fees from Boehringer Ingelheim, Daiichi-Sankyo, F. Hoffman–La Roche, Nippon Kayaku, Nitto Denko, Shionogi, Sumitomo Dainippon, and Takeda; and grants from Astellas, Kyorin, Kyowa-Kirin, and Regeneron outside the submitted work. Dr. Groen reports to have participated on advisory boards of AbbVie. Dr. Reinmuth reports receiving honoraria for speaker activities and participation in advisory boards for AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Roche, and Takeda. Dr. Sun, Dr. Luo, Ms. Tanwani, Ms. Caffrey, and Dr. Komarnitsky are employees of AbbVie and hold AbbVie stock. The remaining authors declare no conflict of interest.