Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and AstraZeneca (NASDAQ:AZN) today announced that a second clinical trial collaboration and supply agreement has been entered with a subsidiary of Merck & Co., Inc., Kenilworth, NJ., USA (known as MSD outside of the United States and Canada) to evaluate the combination of datopotamab deruxtecan (Dato-DXd), a TROP2 directed DXd antibody drug conjugate (ADC), and Merck & Co., Inc., Kenilworth, NJ., USA's anti-PD-1 therapy KEYTRUDA® (pembrolizumab).

Under the terms of the agreement between Daiichi Sankyo and Merck & Co., Inc., Kenilworth, NJ., USA, Daiichi Sankyo will lead TROPION-Lung08, a global phase 3 trial that will evaluate datopotamab deruxtecan in combination with KEYTRUDA compared to KEYTRUDA alone in treatment-naïve patients with PD-L1 high advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations, on behalf of the Daiichi Sankyo and AstraZeneca collaboration. Additional details of the agreement were not disclosed.

Current standard of care in the first-line treatment of patients with metastatic NSCLC without actionable genomic alterations is PD-L1 immunotherapy with or without platinum-based chemotherapy.1 While these therapies can improve survival in this subtype of NSCLC, at least 40 to 60% of tumors do not respond to initial treatment and disease progression occurs, underscoring the need for new innovative treatment approaches.2,3,4,5

"Entering into this second clinical trial collaboration is based on encouraging results in an ongoing phase 1b study and advances development of datopotamab deruxtecan into a phase 3 study in first-line metastatic non-small cell lung cancer," said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. "In this specific trial, we will evaluate whether combining our TROP2 directed ADC with an anti-PD-1 therapy improves outcomes in patients with previously untreated advanced non-small cell lung cancer with no actionable genomic alterations."

"While PD-L1 immunotherapy can improve outcomes in advanced or metastatic non-small cell lung cancer, the progression-free survival for the majority of patients is still less than one year," said Cristian Massacesi, MD, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca. "The TROPION-Lung08 trial will evaluate whether the combination of datopotamab deruxtecan and an immune checkpoint inhibitor that targets the PD-1 pathway will improve outcomes in this setting."

A previous clinical trial collaboration agreement was entered in May 2020 for the TROPION-Lung02 phase 1b trial evaluating the safety and efficacy of datopotamab deruxtecan and KEYTRUDA with or without platinum-based chemotherapy in previously treated or treatment-naïve patients with advanced or metastatic NSCLC without actionable genomic alterations.

About TROPION-Lung08

TROPION-Lung08 is a global, open-label, randomized phase 3 trial that will evaluate the efficacy and safety of the combination of datopotamab deruxtecan and KEYTRUDA versus KEYTRUDA alone in treatment-naïve patients with PD-L1 high advanced or metastatic NSCLC without actionable genomic alterations (e.g., EGFR, ALK, ROS1, NTRK, BRAF, RET, MET or other known actionable mutations). The primary endpoints of TROPION-Lung08 are progression-free survival (PFS), as assessed by blinded independent central review (BICR), and overall survival (OS). TROPION-Lung08 is expected to enroll approximately 740 patients at multiple sites in Asia, Europe, North America, and South America.

KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A.