Dato-DXd (AZ/DS) Granted Priority Review for 1L mTNBC ineligible for anti-PD-(L)1 therapy

On February 3, 2026, AZ /DS announced that the FDA has accepted the sBLA for datopotamab deruxtecan (Datroway; Dato-DXd, TROP2 ADC) and granted Priority Review for 1L mTNBC in patients who are not candidates for IO.

Highlights and Implications

• The PDUFA date is Jun 2, 2026, consistent with prior assumptions for a Q2/Q3 2026 approval
• This designation is based on the results from the P3 TROPION-Breast02 trial presented at ESMO 2025 where Dato-DXd demonstrated statistically significant improvement in mOS (23.7 vs 18.7 mos, HR: 0.79) and mPFS (mPFS: 10.8 vs 5.6 mos, HR 0.57) over CT
• The sBLA filing is under review through Project Orbis, which supports concurrent submission and review of oncology medicines across participating international partners
  • Susan Galbraith (EVP of Oncology Hematology R&D, AZ) indicated plans to leverage Project Orbis to enable rapid global patient access to Dato-DXd and noted that additional regulatory submissions in breast and lung cancer are underway worldwide
  • Recall, regulatory submission for Dato-DXd in 1L TNBC (IO ineligible) were accepted in EU and China in Dec 2025
• Both AZ/DS emphasized that if approved, Dato-DXd could become "standard of care" in this setting 
  • Susan Galbraith and Ken Takeshita (Global Head, R&D, DS) both emphasized that Dato-DXd is the first therapy to demonstrate an OS benefit versus CT in the TB-02 population
  • Takeshita also noted Dato-DXd "nearly doubled"the time without disease progression or death compared to CT
  • Galbraith further highlighted that the TB-02 population represents a subset of patients with highly aggressive disease
• While TB-02 data support Dato-DXd’s entry into TNBC, results from both ASCENT-03 and -04 provide Trodelvy as a future backbone option for all 1L TNBC regardless of PD-L1 status

Additional Background

• Dato-DXd was recently included in the latest version (Version 1.2026) of the NCCN guidelines for 1L PD-L1 CPS<10 and non-BRCAm TNBC as category 2A
• Dato-DXd is currently 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 P3 TROPION-Breast01, which were presented at ESMO 2023 and published in the Journal of Clinical Oncology
  • However, the trial failed to meet its OS endpoint (HR: 1.01)
    • AZ and DS have been messaging 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-Breast03 in combination with durvalumab (Imfinzi, anti-PD-L1) in Stage I-III TNBC without pCR following neoadjuvant therapy  
  • P3 TROPION-Breast04 in combination with durvalumab as a neoadjuvant treatment for eTNBC
  • P3 TROPION-Breast05 in combination with durvalumab in 1L PD-L1+ (CPS≥10) mTNBC
  • P3 TROPION-Breast06 as a monotherapy in HR+/HER2 IHC 0 BC