J Clin Oncol. 2024 Apr 23. IF: 45.3
Datopotamab Deruxtecan in Advanced or Metastatic HR+/HER2- and Triple-Negative Breast Cancer: Results From the Phase I TROPION-PanTumor01 Study. OPEN ACCESS
Bardia A, Krop IE, Kogawa T, Juric D, Tolcher AW, Hamilton EP, Mukohara T, Lisberg A, Shimizu T, Spira AI, Tsurutani J, Damodaran S, Papadopoulos KP, Greenberg J, Kobayashi F, Zebger-Gong H, Wong R, Kawasaki Y, Nakamura T, Meric-Bernstam F.
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA; Yale Cancer Center, New Haven, CT; Dana-Farber Cancer Institute, Boston, MA; South Texas Accelerated Research Therapeutics, San Antonio, TX; NEXT Oncology, San Antonio, TX; Texas Oncology, San Antonio, TX; Sarah Cannon Research Institute, Nashville, TN; Tennessee Oncology, PLLC, Nashville, TN; David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA; Virginia Cancer Specialists (VCS) Research Institute, Fairfax, VA; The University of Texas MD Anderson Cancer Center, Houston, TX; START, San Antonio, TX; Daiichi Sankyo, Inc, Basking Ridge, NJ; Cancer Institute Hospital of JFCR, Tokyo, Japan; National Cancer Center Hospital East, Kashiwa, Japan; National Cancer Center Hospital, Tokyo, Japan; Wakayama Medical University Hospital, Wakayama, Japan; Showa University, Tokyo, Japan; Daiichi Sankyo, Co, Ltd, Tokyo, Japan; Daiichi Sankyo Europe GmbH, Munich, Germany.
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.
KEY OBJECTIVE: The phase I TROPION-PanTumor01 study evaluated Dato-DXd, a TROP2-directed antibody-drug conjugate (ADC), in solid tumors, including hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (BC) and triple-negative BC (TNBC).
KNOWLEDGE GENERATED: The confirmed objective response rate was 26.8% and 31.8%, and the median progression-free survival was 8.3 months and 4.4 months for patients with HR+/HER2- BC and TNBC, respectively. Stomatitis was the most common treatment-emergent adverse event, and one adjudicated drug-related interstitial lung disease case was reported.
RELEVANCE: Data-DXd is a new ADC with significant activity in previously treated BC. Additional studies are needed to evaluate the mechanisms of resistance to ADCs and to determine the optimal sequence of therapies.
PMID: 38652877
DOI: 10.1200/JCO.23.01909
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