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

Authors

Aditya Bardia
Ian E Krop
Takahiro Kogawa
Dejan Juric
Anthony W Tolcher
Erika P Hamilton
Toru Mukohara
Aaron Lisberg
Toshio Shimizu
Alexander I Spira
Junji Tsurutani
Senthil Damodaran
Kyriakos P Papadopoulos
Jonathan Greenberg
Fumiaki Kobayashi
Hong Zebger-Gong
Rie Wong
Yui Kawasaki
Tadakatsu Nakamura
Funda Meric-Bernstam

Publication Date

7-1-2024

Journal

Journal of Clinical Oncology

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.

Keywords

Humans, Female, Triple Negative Breast Neoplasms, Middle Aged, Aged, Immunoconjugates, Adult, Receptor, ErbB-2, Camptothecin, Receptors, Estrogen, Antibodies, Monoclonal, Humanized, Receptors, Progesterone, Antigens, Neoplasm, Cell Adhesion Molecules, Trastuzumab

Comments

Data Availability Statement

PMID: 38652877