Daiichi Sankyo and AstraZeneca have commenced three Phase III clinical trials to investigate the efficacy and safety of datopotamab deruxtecan (Dato-DXd)-based combinations in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). These trials, named TROPION-Lung 10, TROPION-Lung 14, and TROPION-Lung 15, aim to evaluate Dato-DXd in combination with rilvegostomig, osimertinib, and chemotherapy, respectively, across different lines and types of lung cancer.
TROPION-Lung 10: Dato-DXd Plus Rilvegostomig
TROPION-Lung 10 is a global, multicenter, open-label, three-arm trial randomizing patients in a 2:1:2 ratio. It assesses Dato-DXd in combination with rilvegostomig or rilvegostomig monotherapy versus pembrolizumab monotherapy. The dual primary endpoints are progression-free survival (PFS) and overall survival (OS), both evaluated by blinded independent central review (BICR). Secondary endpoints include PFS by investigator assessment, objective response rate (ORR), and duration of response (DoR). The trial plans to enroll approximately 675 patients across Asia, Europe, North America, Oceania, and South America.
TROPION-Lung 14: Dato-DXd Plus Osimertinib
TROPION-Lung 14 is a global, randomized, multicenter, open-label trial evaluating Dato-DXd in combination with osimertinib versus osimertinib monotherapy in approximately 580 patients. The primary endpoint is PFS as assessed by BICR. Secondary endpoints include central nervous system (CNS) PFS, ORR, OS, and safety.
TROPION-Lung 15: Dato-DXd Monotherapy and Combination
TROPION-Lung 15 will randomly assign patients in a 1:1:1 ratio to evaluate Dato-DXd monotherapy or in combination with osimertinib versus platinum-based doublet chemotherapy. Dual primary endpoints are PFS as assessed by BICR for Dato-DXd monotherapy versus chemotherapy and Dato-DXd in combination with osimertinib versus chemotherapy. This trial is expected to enroll approximately 630 patients.
NSCLC Landscape
NSCLC accounts for approximately 85% of all lung cancer cases, with adenocarcinoma being the most prevalent subtype (40%), followed by squamous cell carcinoma (25-30%) and large cell carcinoma (10-15%).
Expert Commentary
Cristian Massacesi, MD, chief medical officer, oncology chief development officer, AstraZeneca, stated, "Clinical research suggests that combining an antibody drug conjugate with a targeted treatment or a bispecific immunotherapy may drive stronger and more durable tumor responses in patients with a variety of cancers including lung cancer...The initiation of these additional three phase 3 trials of datopotamab deruxtecan in combination with our agents, osimertinib and rilvegostomig illustrates our commitment to exploring potential synergies within our oncology pipeline as well as the full potential and combinability of this TROP2 directed antibody drug conjugate across multiple segments and settings of non-small cell lung cancer."
Mark Rutstein, MD, global head, oncology clinical development, Daiichi Sankyo, added, "These three trials in either high PD-L1 expressing or EGFR mutated nonsquamous non-small cell lung cancer are critical to helping us understand the potential role of datopotamab deruxtecan in treating patients across different lines and types of lung cancer...Our growing TROPION clinical program, which now consists of seven phase 3 trials demonstrates our commitment to understanding the full potential of datopotamab deruxtecan in lung cancer."
