AstraZeneca and Daiichi Sankyo have announced the submission of a new Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for accelerated approval of datopotamab deruxtecan (dato-DXd) in adult patients with metastatic or locally advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations who have received prior treatment. This submission follows the voluntary withdrawal of a previous BLA for advanced nonsquamous NSCLC. The decision to focus on the EGFR-mutated population was informed by discussions with the FDA and data indicating a pronounced benefit in this subgroup.
The new BLA is primarily supported by findings from the phase 2 TROPION-Lung05 study (NCT04484142) and is further bolstered by data from the phase 3 TROPION-Lung01 (NCT04656652) and TROPION-PanTumor01 (NCT03401385) trials. Pooled analysis results from the EGFR-mutant NSCLC cohorts within the TROPION-Lung05 and TROPION-Lung01 trials are slated for presentation at the upcoming European Society for Medical Oncology (ESMO) Asia Congress 2024.
TROPION-Lung05 Trial Data
Data from the TROPION-Lung05 trial, presented at the 2023 ESMO Congress, demonstrated a confirmed objective response rate (ORR) of 35.8% (95% CI, 27.8%-44.4%) with dato-DXd in patients with advanced or metastatic NSCLC. Notably, among patients with EGFR mutations, the confirmed ORR was 43.6%.
The international, single-arm, open-label TROPION-Lung05 trial enrolled 137 patients with locally advanced or metastatic NSCLC harboring actionable genomic alterations, including EGFR, ALK, and ROS1. The primary endpoint of the trial was ORR per blinded independent central review (BICR), with secondary endpoints including duration of response (DOR), disease control rate (DCR), clinical benefit rate, progression-free survival (PFS), time to response, overall survival (OS), and safety.
Treatment-emergent adverse events (TEAEs) of grade 3 or higher were observed in 47.4% of patients, with serious TEAEs reported in 24.8%. Dose reductions and drug discontinuations due to TEAEs were required in 21.9% and 9.5% of patients, respectively. TEAEs leading to death occurred in 1.5% of patients.
TROPION-Lung01 Trial Data
Final OS findings from the TROPION-Lung01 trial, presented at the 2024 IASLC World Conference on Lung Cancer (WCLC), showed a median OS of 12.9 months with dato-DXd compared to 11.8 months with docetaxel (HR, 0.94; 95% CI, 0.78-1.14; P = .530) in the overall trial population. In the nonsquamous histology subgroup, an improvement in OS with dato-DXd was observed regardless of the presence of actionable genomic alterations such as EGFR, which were present in 17% of patients across both arms.
The multi-center, open-label TROPION-Lung01 trial evaluated the safety and efficacy of dato-DXd versus docetaxel in approximately 600 adults with locally advanced or metastatic NSCLC with or without actionable genomic alterations. The trial's primary endpoints were PFS per BICR and OS. Secondary endpoints included ORR, DOR, time to response, and disease control rate.
Susan Galbraith, Executive Vice President of Oncology Research and Development at AstraZeneca, stated, "TROPION-Lung01 was designed to test the potential to improve upon standard-of-care chemotherapy in for patients with a broad, previously treated, advanced lung cancer patient population. The results, together with data from TROPION-Lung05, showed an especially pronounced benefit for patients with an EGFR mutation, which informed our discussions with the FDA and the decision to seek accelerated approval of datopotamab deruxtecan in this patient population."
