TROPION-Lung08: phase III study of datopotamab deruxtecan plus pembrolizumab as first-line therapy for advanced NSCLC

Abstract

Antibody–drug conjugate; Immuno-oncology; Non-small-cell lung cancer

Conjugado anticuerpo-fármaco; Inmuno-oncología; Cáncer de pulmón de células no pequeñas

Conjugat anticòs-fàrmac; Immuno-oncologia; Càncer de pulmó de cèl·lules no petites

Pembrolizumab monotherapy is a standard first-line treatment for PD-L1–high advanced non-small-cell lung cancer (NSCLC) without actionable genomic alterations (AGA). However, few patients experience long-term disease control, highlighting the need for more effective therapies. Datopotamab deruxtecan (Dato-DXd), a novel trophoblast cell-surface antigen 2-directed antibody–drug conjugate, showed encouraging safety and antitumor activity with pembrolizumab in advanced NSCLC. We describe the rationale and design of TROPION-Lung08, a phase III study evaluating safety and efficacy of first-line Dato-DXd plus pembrolizumab versus pembrolizumab monotherapy in patients with advanced/metastatic NSCLC without AGAs and with PD-L1 tumor proportion score ≥50%. Primary end points are progression-free survival and overall survival; secondary end points include objective response rate, duration of response, safety and presence of antidrug antibodies.

This study is sponsored by Daiichi Sankyo, Inc. In July 2020, Daiichi Sankyo entered into a global development and commercialization collaboration agreement with AstraZeneca for datopotamab deruxtecan (Dato-DXd). Pembrolizumab is being provided under agreement by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD). BP Levy received consulting fees from Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Janssen, Mirati, Novartis, Pfizer, and Roche/Genentech. E Felip received consulting fees and/or honoraria from Amgen, AstraZeneca, Bayer, BerGenBio, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Roche, GSK, Janssen, Medical Trends, Medscape, Merck Serono, MSD, Novartis, PeerVoice, Peptomyc, Pfizer, Sanofi, Takeda, and touchONCOLOGY and grant funding to her institution from Merck KGaA and Fundación Merck Salud. E Felip is an independent member of the Grífols Board of Directors. M Reck received consulting fees, honoraria, and support for attending meetings from Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, GSK, Mirati, Merck, MSD, Novartis, Pfizer, Sanofi, Roche, and Regeneron and served on data safety monitoring boards for Daiichi Sankyo and Sanofi. JCH Yang received consulting or advisory fees from Ono Pharmaceuticals and Pfizer, grant funding to his institution from AstraZeneca and advisory or consulting fees to his institution from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Gilead, GSK, Johnson & Johnson, Merck KGaA, MSD, Novartis, Puma Technology, Roche/Genentech, Takeda and Yuhan Pharmaceuticals. F Cappuzzo received consulting fees from AstraZeneca, Bayer, Bristol Myers Squibb, Eli Lilly, Janssen, Merck, MSD, Novartis, Pfizer, PharmaMar, Roche, and Takeda. C Zhou received consulting fees and/or honoraria from Amoy Diagnostics, AnHeart Therapeutics, Boehringer Ingelheim, CStone Pharmaceuticals, Luye Pharma Group, Eli Lilly China, Jiangsu Hengrui Pharmaceuticals, Innovent Biologics, MSD, Qilu Pharmaceutical, Roche, Sanofi, and TopAlliance Biosciences. S Rawat is an employee of and owns stock and/or stock options in Daiichi Sankyo. P Basak and J Xie are employees of Daiichi Sankyo. L Xu was an employee at MSD at the time this study was designed and is a current employee of AstraZeneca. J Sands received consulting fees from AstraZeneca, Curadev, Daiichi Sankyo, Guardant Health, Jazz Pharmaceuticals, Medtronic, PharmaMar, Sanofi, and Takeda and is the treasurer of the Rescue Lung Society. Y Yoneshima declares no potential conflicts. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.