AstraZeneca Withdraws Dato-DXd BLA for Non-Squamous NSCLC, Submits New Application for EGFR-Mutated NSCLC Based on TROPION-Lung05 Data

▎Armstrong

On November 12, 2024, AstraZeneca announced the withdrawal of its previous marketing application for the treatment of non-squamous NSCLC based on the Phase III clinical data from TROPION-Lung01. Instead, it submitted a new marketing application for later-line treatment of recurrent or metastatic EGFR-mutant NSCLC. This application is based on the Phase II clinical data from TROPION-Lung05 (supported by data from TROPION-Lung01) and the Phase I clinical data from TROPION-PanTumor01. The strategic adjustment of this marketing application was made based on feedback from the FDA.

Previously, AstraZeneca submitted a marketing application for second- to third-line treatment of non-squamous NSCLC based on the PFS endpoint achieved in the TROPION-Lung01 trial. In September this year, AstraZeneca announced the OS data from this Phase III clinical trial. The mOS for the Dato-DXd treatment group and the docetaxel chemotherapy group were 12.9 months and 11.8 months, respectively, with an HR of 0.94 and a p-value of 0.53, which did not reach statistical significance.

TROPION-Lung05 is a study targetingDriveGene Mutation (AGA) RecurrentSingle-arm Phase II Clinical Trial for NSCLCFor patients without brain metastasis, the ORR and DCR were 40% and 83%, respectively, while for patients with brain metastasis, the ORR and DCR were 28% and 72%, respectively. The data indicate that Dato-Dxd shows a promising response in NSCLC patients with driver gene mutations and brain metastasis, supporting further clinical exploration.

Latest clinical data of TROPION-Lung05 and TROPION-Lung01 for previously treated NSCLC with EGFR mutations will be presented at the ESMO Asia 2024 conference on December 6.

Summary

Dato-DXd currently has nine Phase III clinical trials ongoing for NSCLC, while exploring various combination therapies, covering both EGFR wild-type NSCLC and EGFR-mutant NSCLC. Early-stage clinical trials for pan-tumor indications are also actively progressing.