European Commission (EC) approves datopotamab deruxtecan (Dato-DXd, Datroway) for the treatment of 1L mTNBC patients ineligible for anti-PD(L)1 therapy.

On July 31, 2026, the European Commission (EC) approved datopotamab deruxtecan (Dato-DXd, Datroway; TROP2 ADC) for the treatment of 1L mTNBC patients ineligible for anti-PD(L)1 therapy, based on results from the P3 TROPION-Breast02 (TB-02) trial (AZ Press Release, DS Press Release).

Highlights 

• EC approval follows the recent positive CHMP opinion on Jun 26, 2026
  • Dato-DXd received FDA approval for the same indication on May 22, 2026
  • Additional regulatory reviews are underway in other geographies including CN and JP, as part of Project Orbis
• The EC approval is supported by data from P3 TROPION-Breast02 trial (N=644; PCD: Aug 2025) evaluating Dato-DXd in 1L mTNBC ineligible for anti-PD-(L)1 therapy
  • TROPION-Breast02 met its dual primary endpoints of OS (23.7 vs 18.7 mos; HR: 0.79) and PFS (10.8 vs 5.6 mos; HR: 0.57) vs CT
  • Data was first presented at ESMO 2025 (LBA#21) and published in Annals of Onc. (Apr 3, 2026); subsequent data presentations include additional safety analyses at SABCS 2025 (PS5-03-05), PRO data at ESMO-BC 2026 (415O), and additional efficacy data (PFS2) at ASCO 2026 (Abs 1002)
• AZ/DS continues to position Dato-DXd as the only TROP2 ADC that demonstrated OS benefit in 1L mTNBC (IO-ineligible), potentially addressing a large unmet need affecting more than 80,000 people in EU, often younger women with limited treatment options
• TB-02 competes directly with P3 ASCENT-03 trial (N=623; PCD: Jul 2028), which received EU marketing authorization on Jun 23, 2026, in the same 1L mTNBC patient population ineligible for anti-PD-(L)1 therapy
  • Trodelvy in combination with pembrolizumab in the 1L mTNBC IO-eligible population (ASCENT-04) received a positive CHMP opinion in Jul 2026, with EC approval expected Aug/Sep 2026
  • AZ/DS trial competing with ASCENT-04, P3 TROPION-Breast05 (PCD=625; PCD: Jul 2027) evaluating Dato-DXd ± durvalumab (Imfinzi; anti-PD-L1) in 1L TNBC PD-L1+ CPS≥10 is ongoing with data guided for 2027
• Note, the May 2026 update to ESMO TNBC guidelines recommended both Dato-DXd or Trodelvy as level [I, A] treatment options for most patients with 1L germline BRCA1/2-wild-type, PD-L1-negative mTNBC; however, Dato-DXd is listed as the preferred option for patients relapsing within 6 months of adjuvant therapy
  • As both agents become established in this 1L setting, the competitive differentiation in this setting will likely shift to access, tolerability, clinical management experiences

Background

• Dato-DXd is currently also approved for the treatment of 2L+ HR+/HER2- mBC post-ET and post-CT in the US, EU, and JP, based on positive PFS data from Phase 3 TROPION-Breast01, which were presented at ESMO 2023 and published in the Journal of Clinical Oncology
  • However, the trial failed to meet its dual primary endpoint of final OS (HR: 1.01)
  • AZ and DS message that OS failure was potentially due to an imbalance in the use of ADCs as subsequent treatments in the experimental vs control arms
• Dato-DXd is also being evaluated in the following pivotal trials:
  • P3 TROPION-Breast05 (PCD=625; PCD: Jul 2027) evaluating Dato-DXd ± durvalumab (Imfinzi; anti-PD-L1) in 1L TNBC PD-L1+ CPS≥10 is ongoing with data guided for 2027
  • P3 TROPION-Breast03 trial (N=1174; PCD: Sep 2027) in combination with durvalumab in Stage I-III TNBC without pCR following neoadjuvant therapy
    • Note: TB-03 competes directly with P3 ASCENT-05 trial (N=1514; PCD: Jun 2027) of Trodelvy in combination with pembrolizumab in Stage I-III TNBC without pCR following neoadjuvant therapy
  • P3 TROPION-Breast04 trial (N=1902; PCD: Nov 2028) in combination with durvalumab as a neoadjuvant treatment for eTNBC