Introduction: Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate targeting DLL3, an atypical Notch ligand expressed in SCLC tumors. We evaluated the efficacy of Rova-T versus placebo as maintenance therapy in patients with extensive-stage–SCLC after platinum-based chemotherapy. Methods: MERU was a phase 3 randomized, double-blinded, placebo-controlled study. Patients without disease progression after four cycles of platinum-based, front-line chemotherapy were randomized in a 1:1 ratio to receive 0.3 mg/kg Rova-T or placebo (every 6 wk, omitted every third cycle). Primary efficacy end points were progression-free survival (PFS) evaluated by the Central Radiographic Assessment Committee and overall survival (OS) in patients with DLL3-high tumors. Results: Median age of all randomized patients (N = 748) was 64 years; 78% had TNM stage IV disease. At futility analysis of the subset with DLL3-high tumors, the hazard ratio for OS was 1.07 (95% confidence interval: 0.84–1.36) favoring the placebo arm, with median OS of 8.5 and 9.8 months in the Rova-T and placebo arms, respectively; futility criteria were met. Rova-T significantly improved PFS versus placebo by investigator assessment (4.0 versus 1.4 mo, hazard ratio = 0.48, p < 0.001). Any-grade adverse events (≥20%) in the Rova-T arm were pleural effusion (27%), decreased appetite (27%), peripheral edema (26%), photosensitivity reaction (25%), fatigue (25%), nausea (22%), and dyspnea (21%). Conclusions: Because of the lack of survival benefit in the Rova-T arm, the study did not meet its primary end point and was terminated early. As a result, the Central Radiographic Assessment Committee evaluation of PFS was not performed. The frequency of grade greater than or equal to 3 and drug-related toxicities were higher with Rova-T versus placebo. Rova-T was associated with unique toxicities, such as pleural and pericardial effusions, photosensitivity reaction, and peripheral edema, which should be carefully considered in the population with extensive-stage–SCLC.
Bibliographical noteFunding Information:
AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Rovalpituzumab tesirine has been developed by AbbVie, Inc. Medical writing support was provided by Swati Ghatpande, PhD, of Bio Connections, LLC, funded by AbbVie, Inc. The authors thank all the trial investigators and the patients who participated in this clinical trial. Validation (verification of the overall replication/reproducibility of results/experiments and other research outputs) was by Drs. Komarnitsky and Sun. Formal analysis (application of statistical, mathematical, computational, or other formal techniques to analyze or synthesize study data) was by Drs. Bar and Sun. Investigation (conducting a research and investigation process, performing experiments, or data/evidence collection) was by Drs. Johnson, Bar, Helland, van der Leest, and Maag. Resources (provision of study materials, reagents, patients, laboratory samples, animals, instrumentation, computing resources, or other tools) were by Drs. Johnson, Bar, Helland, van der Leest, Colinet, Cho, Gutierrez, Gottfried, Hung, Okamoto, Lena, Zvirbule, Laktionov, Appenzeller, Hung, Gutierrez, Rich, and Wolf. Data curation (management of activities to annotate, scrub data, and maintain research data for initial and later uses) was by Drs. Helland and Sun. Writing (original draft or reviewing and editing of subsequent drafts) was by Drs. Johnson, Bar, Helland, Maag, Colinet, Appenzeller, var der Leest, Zvirbule, Laktionov, Hung, Gutierrez, Gottfried, Rich, and Wolf. Visualization (preparation, creation or presentation of data in published work) was by Dr. Sun. Supervision (oversight and leadership for research activity planning and execution, including mentorship to the core team) was by Drs. Johnson, Maag, and Vajikova. Project administration (management and coordination for research activity planning/execution) was by Ms. Vajikova.
Disclosure: Dr. Johnson reports receiving research funding from AbbVie, Amgen, Acerta, Adaptimmune, Apexigen, Array BioPharma, AstraZeneca, Atreca, BeiGene, BerGenBio, Boehringer Ingelheim, Calithera Biosciences, Checkpoint Therapeutics, Corvus Pharmaceuticals, CytomX, Daiichi Sankyo, Dynavax, Eli Lilly, EMD Serono, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Hengrui Therapeutics, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Loxo Oncology, Lycera, Merck, Mirati Therapeutics, Neovia Oncology, Novartis, OncoMed Pharmaceuticals, Pfizer, Regeneron Pharmaceuticals, Sanofi, Seven and Eight Biopharmaceuticals, Shattuck Labs, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, University of Michigan, WindMIL, TCR2 Therapeutics, Arcus Biosciences, Ribon Therapeutics, and Tmunity Therapeutics; reports receiving consulting or advisory role for AbbVie, Achilles Therapeutics, AstraZeneca, Atreca, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera Biosciences, EMD Serono, Genentech/Roche, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Incyte, Janssen, Lilly, Loxo Oncology, Merck, Mirati Therapeutics, Novartis, Pfizer, Ribon Therapeutics, Sanofi, Association of Community Cancer Centers, WindMIL; reports lodging/travel expenses provided by AstraZeneca, Roche/Genentech, Merck, Sanofi, Pfizer, Abbvie, Incyte. Dr. Johnson's spouse reports receiving consulting or advisory role for Astellas and Otsuka Pharmaceuticals. Dr. Helland reports receiving advisory board with AbbVie, AstraZeneca, and Roche. Dr. Cho received 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, Blueprint Medicines; has stock ownership at TheraCanVac Inc., Gencurix Inc., Bridgebio therapeutics, Kanaph Therapeutic Inc., Cyrus therapeutics, and Interpark Bio Convergence Corp; and serves on the scientific advisory boards of Kanaph Therapeutics Inc., Brigebio Therapeutics, Cyrus Therapeutics, and Guardant Health; serves on 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. Colinet reports receiving consultancy for AstraZeneca. Dr. Lena reports receiving personal fees and nonfinancial support from AstraZeneca, Roche, Merck Sharp & Dohme, Bristol-Myers Squibb, Pfizer, Novartis, Amgen, and Takeda outside of the submitted work. Dr. Okamoto reports receiving grants from Boehringer Ingelheim during the conduct of the study; grants and personal fees from AstraZeneca, Roche, and AbbVie; Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, Merck Sharp & Dohme Oncology, Eli Lilly,Bristol-Myers Squibb, and Chugai Pharma; grants from Astellas Pharma, Novartis, and AbbVie; personal fees from Pfizer outside of the submitted work. Dr. van der Leest reports receiving consultancy for/honoraria from AbbVie, Roche and AstraZeneca. Dr. Bar reported research funding for the institute and consultancy fees from AstraZeneca, AbbVie, Novartis, and Merck Sharp and Dohme; consultancy fees from Roche, Boehringer Ingelheim, VBL, Bayer Bristol-Myers Squibb and Takeda; research funding for the institute from Pfizer, OncoHost, and ImmuneAI. Drs. Komarnitsky, Luo, Sun, Maag, and Ms. Nickner and Ms. Vajikova are employees of AbbVie and hold AbbVie stock. The remaining authors declare no conflict of interest.
© 2021 International Association for the Study of Lung Cancer
All Science Journal Classification (ASJC) codes
- Pulmonary and Respiratory Medicine