Daiichi Sankyo, AstraZeneca Launch Phase III Trials of Datopotamab Deruxtecan in Advanced Nonsquamous Non-Small Cell Lung Cancer

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Daiichi Sankyo and AstraZeneca have initiated three Phase III clinical trials to evaluate the efficacy and safety of datopotamab deruxtecan (Dato-DXd)-based combinations in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). The TROPION-Lung 10, TROPION-Lung 14, and TROPION-Lung 15 trials will investigate Dato-DXd in combination with various therapies, including rilvegostomig, osimertinib, and chemotherapy.¹

“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,” said Mark Rutstein, MD, global head, oncology clinical development, Daiichi Sankyo, in a press release. “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.”

TROPION-Lung10 is a global, multicenter, open-label, three-arm trial in which patients will be randomly assigned in a 2:1:2 ratio to evaluate the efficacy and safety of Dato-DXd in combination with rilvegostomig or rilvegostomig monotherapy versus pembrolizumab monotherapy. The two primary endpoints of the study are progression-free survival (PFS) as assessed by blinded independent central review (BICR) and overall survival (OS). Secondary endpoints include PFS as assessed by BICR and investigator, OS in the intention-to-treat (ITT) population, objective response rate (ORR) as assessed by BICR, and duration of response (DoR) as assessed by BICR. It will enroll approximately 675 patients in Asia, Europe, North America, Oceania, and South America.

TROPION-Lung14 is a global, randomized, multicenter, open-label trial that will evaluate the efficacy and safety of Dato-DXd in combination with osimertinib versus osimertinib monotherapy in approximately 580 patients. The primary endpoint is PFS as assessed by BICR, with secondary endpoints including central nervous system (CNS) PFS as assessed by CNS BICR, PFS as assessed by investigator, ORR as assessed by BICR and investigator, OS, and safety.

TROPION-Lung15 will randomly assign patients in a 1:1:1 ratio to evaluate the efficacy and safety of Dato-DXd s 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. It is expected to enroll approximately 630 patients.¹

According to Yale Medicine, NCSLC is the most common type of lung cancer, accounting for 85% of all cases. There are three primary forms of NCSLC, including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Adenocarcinoma represents 40% of all NSCLC diagnoses, squamous cell carcinoma represents 25% to 30%, and large cell carcinoma represents approximately 10% to 15%.²

“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,” said Cristian Massacesi, MD, chief medical officer, oncology chief development officer, AstraZeneca, in the press release. “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.”

References

1. Three Phase 3 Trials of Datopotamab Deruxtecan-Based Combinations Initiated in Patients with Advanced Nonsquamous Non-Small Cell Lung Cancer. Business Wire. October 30, 2024. Accessed October 30, 2024. https://www.businesswire.com/news/home/20241029294755/en

2. Non-Small Cell Lung Cancer. Yale Medicine. Accessed October 30, 2024. https://www.yalemedicine.org/conditions/non-small-cell-lung-cancer