Three phase 3 trials have commenced, evaluating datopotamab deruxtecan (Dato-DXd) in diverse combinations for treating locally advanced or metastatic non-small cell lung cancer (NSCLC). These trials, TROPION-Lung10, TROPION-Lung14, and TROPION-Lung15, aim to understand Dato-DXd's potential across different lines and types of lung cancer. The studies target specific NSCLC subtypes, including those with high PD-L1 expression and EGFR mutations. These trials are crucial to understanding the potential role of datopotamab deruxtecan in treating patients across different lines and types of lung cancer.
TROPION-Lung10: Dato-DXd Plus Rilvegostomig vs Pembrolizumab
TROPION-Lung10 (NCT06357533) is designed to evaluate Dato-DXd combined with rilvegostomig, a PD-1/TIGIT bispecific antibody, or rilvegostomig alone, against pembrolizumab in treatment-naive patients with locally advanced or metastatic, non-squamous NSCLC, high PD-L1 expression (TC ≥ 50%), and without actionable genomic alterations. The trial plans to enroll approximately 675 patients, randomized to receive Dato-DXd plus rilvegostomig, rilvegostomig monotherapy, or pembrolizumab, administered intravenously on day 1 of 21-day cycles.
The primary endpoints are progression-free survival (PFS) and overall survival (OS) in TROP2 biomarker-positive patients. Secondary endpoints include PFS and OS in the intent-to-treat (ITT) population, objective response rate (ORR), duration of response (DOR), patient-reported lung cancer symptoms and physical functioning, pharmacokinetics (PK), and second PFS (PFS2).
TROPION-Lung14: Dato-DXd Plus Osimertinib vs Osimertinib
TROPION-Lung14 (NCT06350097) will assess Dato-DXd plus osimertinib versus osimertinib alone in patients with previously untreated, locally advanced or metastatic EGFR-mutated non-squamous NSCLC (EGFR exon 19 deletion and/or L858R mutation). The study aims to enroll an estimated 582 patients, randomized to receive oral osimertinib 80 mg daily plus Dato-DXd IV on day 1 of 21-day cycles or oral osimertinib monotherapy.
The primary endpoint is PFS by blinded independent central review. Secondary endpoints include OS, central nervous system (CNS) PFS, ORR, DOR, PFS2, and PK.
TROPION-Lung15: Dato-DXd With or Without Osimertinib vs Chemotherapy
TROPION-Lung15 (NCT06417814) will evaluate Dato-DXd with or without osimertinib compared to platinum-based doublet chemotherapy (pemetrexed plus carboplatin or cisplatin) for patients with locally advanced or metastatic, non-squamous NSCLC with an EGFR mutation and whose disease progressed on osimertinib. Approximately 630 patients will be enrolled and randomized 1:1:1 to receive Dato-DXd plus osimertinib, Dato-DXd, or chemotherapy. Dato-DXd will be administered on day 1 of a 21-day cycle, osimertinib 80 mg orally daily, and chemotherapy every 3 weeks for 4 cycles.
The study’s primary endpoint is PFS. Secondary endpoints include OS, CNS PFS, ORR, DOR, PFS2, ORR, quality of life, and PK.
Mark Rutstein, MD, global head of oncology clinical development at Daiichi Sankyo, stated, "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."
