FDA Approves Datopotamab Deruxtecan for Second Indication 45 Percent Response Rate in EGFR Mutant Lung Cancer

On June 23, Daiichi Sankyo and AstraZeneca announced that the FDA had approved Datopotamab Deruxtecan for its second indication, targeting locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) in adult patients who have previously undergone EGFR-targeted therapy and platinum-based chemotherapy. This breakthrough makes Datopotamab Deruxtecan the first FDA-approved TROP2-targeted therapy for these heavily pretreated patients.

The approval was based on results from the TROPION-Lung05 Phase II and TROPION-Lung01 Phase III trials, where the therapy demonstrated a 45% confirmed objective response rate (ORR), as evaluated by blinded independent central review (BICR). Among the 114 patients, 4.4% achieved complete response (CR) and 40% showed partial response (PR), with a median duration of response (DoR) of 6.5 months.

Daiichi Sankyo will receive a $45 million milestone payment from AstraZeneca as part of their 2020 collaboration agreement, which was valued at over $6 billion for the joint global development and commercialization of Datopotamab Deruxtecan, excluding Japan.

The therapy, an innovative DXd antibody-drug conjugate (ADC) targeting TROP2, was initially approved by the FDA in January 2025 for treating HR-positive, HER2-negative metastatic breast cancer. Beyond its current approval, it is being further evaluated in TROPION-Lung14 and TROPION-Lung15 trials, both exploring its efficacy as monotherapy or in combination with AstraZeneca’s EGFR TKI osimertinib.

While offering a new treatment avenue for patients with limited options, Datopotamab Deruxtecan's safety profile includes serious adverse reactions in 26% of cases, such as oral mucositis, pneumonia, and COVID-19-related complications.

This approval positions Datopotamab Deruxtecan as a game-changing therapy for advanced EGFR-mutant NSCLC, marking a significant milestone in the fight against lung cancer.