AstraZeneca and Daiichi Sankyo announced the voluntary withdrawal of the US application of Dato-DXd (TROP2 ADC) for 2L+ locally advanced or metastatic non-squamous (Nsq) lung cancer (NSCLC)

On November 12, 2024, AstraZeneca and Daiichi Sankyo announced the voluntary withdrawal of the US BLA of Dato-DXd (TROP2 ADC) for 2L+ locally advanced or metastatic non-squamous (Nsq) NSCLC based on P3 TROPION-Lung01.

They simultaneously announced the submission of a new BLA seeking US accelerated approval (AA) of Dato-DXd for 2L+ EGFRm mNSCLC who have progressed on EGFR TKI based primarily on P2 TROPION-Lung05; AZ has also applied for FDA Breakthrough Therapy Designation. These decisions were informed by FDA feedback.

Key information disclosed during AZ’s earnings call.

• The new application is based on data from the P2 TROPION-Lung05 trial with supporting data from P3 TROPION-Lung-01 (EGFRm subset) and P1 TROPION-PanTumor01
  • In TL-05, Dato-DXd showed cORR of 44% in EGFRm mNSCLC previously treated with osimertinib (EGFR TKI)
  • AZ will share a pooled analysis of patients with previously-treated EGFRm NSCLC from TL-05 and TL-01 at the upcoming ESMO Asia 2024 Congress (#LBA7)
  • The ongoing P3 TROPION-Lung15 trial of Dato-DXd +/- osimertinib vs platinum-based doublet chemo in 2-3L EGFRm la/mNSCLC who have progressed on osi will serve as the confirmatory study
• If approved under this new filing, Dato-DXd may still be positioned as the first-to-market TROP2 ADC in mNSCLC in the US; however, that advantage will be somewhat tempered given the far narrower addressable population (AZ est. EGFRm as ~16%)
  • AZ stated that the filing was submitted “very recently” but did not disclose specific timing. US AA could be granted ~Sept 2025 under priority review timelines, which seems the likelier scenario as the BTD application was “with the encouragement of the FDA”
  • Under standard review timelines, approval could take place in ~Nov 2025
  • Possibility for earlier approvals depending on regulatory decision for TROPION-Breast01 in January 2025
• While the FDA had previously accepted the TL-01 filing based on the positive but unpowered Nsq PFS results, expectations for gaining approval were low given the totality of data including negative final OS results that were recently presented at WCLC (#OA08.03)
• AZ continues to guide an EU regulatory decision for Dato-DXd in H1 2025 though it is unlikely to be approved