FDA approved datopotamab deruxtecan (Dato-DXd, Datroway) for the treatment of mTNBC patients not candidates for PD-1/PD-L1 inhibitors

On May 22, 2026, the FDA approved datopotamab deruxtecan (Dato-DXd, Datroway; TROP2 ADC) for the treatment of mTNBC patients not candidates for PD-1/PD-L1 inhibitors, based on results from the P3 TROPION-Breast02 trial.

• FDA approval was granted slightly ahead of the PDUFA date of Jun 2, 2026
  • A CHMP opinion is anticipated in Jun/Jul 2026, with subsequent EC approval in Q3’26
• The label expansion of Dato-DXd is supported by results from the P3 TROPION-Breast02 trial evaluating Dato-DXd in 1L mTNBC ineligible for anti-PD-(L)1 therapy
  • TB-02 competes directly with Trodelvy's P3 ASCENT-03 trial
  • TB-02 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 was published in Annals of Onc. on Apr 3, 2026
  • Following primary data, AZ/DS have continued with data flow including additional safety analysis at SABCS 2025 (PS5-03-05), PRO data at ESMO-BC 2026 (415O), and additional efficacy data (PFS2, time to first subsequent therapy or death, time to second subsequent therapy or death) expected at ASCO 2026 (Abs 1002)
• AZ/DS continues to message the OS benefit from TB-02 and positions Dato-DXd as a potential new standard of care for IO-ineligible TNBC that can redefine treatment expectations in this setting
• Although the approval is based on the P3 TROPION-Breast02 trial that evaluated Dato-DXd in 1L mTNBC (IO ineligible), the FDA label does not explicitly restrict the use by LoT
  • FDA indication: adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy
  • The broader population wording may provide additional flexibility in clinical practice, although real-world adoption and reimbursement implications remain to be determined
• Along with ASCENT-03, Trodelvy’s positive P3 ASCENT-04 outcome, positions Trodelvy as a backbone option for 1L TNBC population regardless of PD-L1 status
  • Additionally, the safety profile of Trodelvy remains a key differentiation
  • AZ/DS’ 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
• Trodelvy retains the key advantage of first TROP2-ADC with NCCN Category 1 inclusion for both CPS<10 and CPS≥10 (with pembrolizumab), further expanding its physician familiarity ahead of formal regulatory approvals
  • Trodelvy and Dato-Dxd are listed at parity as Category 1, preferred recommendations in 1L TNBC PD-L1 CPS<10 (no germline BRCA1/2) in the NCCN Breast Cancer Guidelines Ver 3.2026

Additional Background

• Dato-DXd is currently also approved for the treatment of 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 published in the Journal of Clinical Oncology (first presented at ESMO 2023)
  • However, the trial failed to meet its dual primary endpoint of final OS (HR: 1.01)
• Dato-DXd is also being evaluated in the following pivotal BC trials:
  • P3 TROPION-Breast05 trial (N=625; PCD: Jul 2027) in combination with durvalumab in IO eligible (CPS≥10) 1L mTNBC
  • 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

source: AZ/DS press releases