Datopotamab Deruxtecan in Advanced or Metastatic HR+/HER2- and Triple-Negative Breast Cancer: Results From the Phase I TROPION-PanTumor01 Study

  • J Clin Oncol. 2024 Jul 1;42(19):2281-2294. doi: 10.1200/JCO.23.01909.
Aditya Bardia  1 ,  Ian E Krop  2  3 ,  Takahiro Kogawa  4 ,  Dejan Juric  1 ,  Anthony W Tolcher  5  6  7 ,  Erika P Hamilton  8  9 ,  Toru Mukohara  10 ,  Aaron Lisberg  11 ,  Toshio Shimizu  12  13 ,  Alexander I Spira  14 ,  Junji Tsurutani  15 ,  Senthil Damodaran  16 ,  Kyriakos P Papadopoulos  17 ,  Jonathan Greenberg  18  19 ,  Fumiaki Kobayashi  20 ,  Hong Zebger-Gong  19 ,  Rie Wong  21 ,  Yui Kawasaki  18 ,  Tadakatsu Nakamura  20 ,  Funda Meric-Bernstam  16
Affiliations
  • 1. Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA.
  • 2. Yale Cancer Center, New Haven, CT.
  • 3. Dana-Farber Cancer Institute, Boston, MA.
  • 4. Department of Advanced Medical Development, Cancer Institute Hospital of JFCR, Tokyo, Japan.
  • 5. South Texas Accelerated Research Therapeutics, San Antonio, TX.
  • 6. NEXT Oncology, San Antonio, TX.
  • 7. Texas Oncology, San Antonio, TX.
  • 8. Sarah Cannon Research Institute, Nashville, TN.
  • 9. Tennessee Oncology, PLLC, Nashville, TN.
  • 10. Department of Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
  • 11. Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA.
  • 12. Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan.
  • 13. Department of Pulmonary Medicine and Medical Oncology, Wakayama Medical University Hospital, Wakayama, Japan.
  • 14. Virginia Cancer Specialists (VCS) Research Institute, Fairfax, VA.
  • 15. Advanced Cancer Translational Research Institute, Showa University, Tokyo, Japan.
  • 16. Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • 17. Clinical Research, START, San Antonio, TX.
  • 18. Global Oncology Clinical Development, Daiichi Sankyo, Inc, Basking Ridge, NJ.
  • 19. Global Oncology Clinical Development, Daiichi Sankyo Europe GmbH, Munich, Germany.
  • 20. Data Intelligence, Daiichi Sankyo, Co, Ltd, Tokyo, Japan.
  • 21. Global Oncology Clinical Development, Daiichi Sankyo, Co, Ltd, Tokyo, Japan.
PMID: 38652877 DOI: 10.1200/JCO.23.01909
Abstract

Purpose: Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate consisting of a humanized antitrophoblast cell-surface antigen 2 (TROP2) monoclonal antibody linked to a potent, exatecan-derived Topoisomerase I inhibitor payload via a plasma-stable, selectively Cleavable Linker.

Patients and methods: TROPION-PanTumor01 (ClinicalTrials.gov identifier: NCT03401385) is a phase I, dose-escalation, and dose-expansion study evaluating Dato-DXd in patients with previously treated solid tumors. The primary study objective was to assess the safety and tolerability of Dato-DXd. Secondary objectives included evaluation of antitumor activity and pharmacokinetics. Results from patients with advanced/metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast Cancer (BC) or triple-negative BC (TNBC) are reported.

Results: At data cutoff (July 22, 2022), 85 patients (HR+/HER2- BC = 41, and TNBC = 44) had received Dato-DXd. The objective response rate by blinded independent central review was 26.8% (95% CI, 14.2 to 42.9) and 31.8% (95% CI, 18.6 to 47.6) for patients with HR+/HER2- BC and TNBC, respectively. The median duration of response was not evaluable in the HR+/HER2- BC cohort and 16.8 months in the TNBC cohort. The median progression-free survival in patients with HR+/HER2- BC and TNBC was 8.3 and 4.4 months, respectively. All-cause treatment-emergent adverse events (TEAEs; any grade, grade ≥3) were observed in 100% and 41.5% of patients with HR+/HER2- BC and 100% and 52.3% of patients with TNBC. Stomatitis was the most common TEAE (any grade, grade ≥3) in both HR+/HER2- BC (82.9%, 9.8%) and TNBC (72.7%, 11.4%) cohorts.

Conclusion: In patients with heavily pretreated advanced HR+/HER2- BC and TNBC, Dato-DXd demonstrated promising clinical activity and a manageable safety profile. Dato-DXd is currently being evaluated in phase III studies.

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