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

被引：48

作者：

Bardia, Aditya ^{[1
]}

Krop, Ian E. ^{[2
,3
]}

Kogawa, Takahiro ^{[4
]}

Juric, Dejan ^{[1
]}

Tolcher, Anthony W. ^{[5
,6
,7
]}

Hamilton, Erika P. ^{[8
,9
]}

Mukohara, Toru ^{[10
]}

Lisberg, Aaron ^{[11
]}

Shimizu, Toshio ^{[12
,13
]}

Spira, Alexander I. ^{[14
]}

Tsurutani, Junji ^{[15
]}

Damodaran, Senthil ^{[16
]}

Papadopoulos, Kyriakos P. ^{[17
]}

Greenberg, Jonathan ^{[18
,19
]}

Kobayashi, Fumiaki ^{[20
]}

Zebger-Gong, Hong ^{[19
]}

Wong, Rie ^{[21
]}

Kawasaki, Yui ^{[18
]}

Nakamura, Tadakatsu ^{[20
]}

Meric-Bernstam, Funda ^{[16
]}

机构：

[1] Harvard Med Sch, Massachusetts Gen Hosp, Canc Ctr, Dept Med, Boston, MA USA

[2] Yale Canc Ctr, New Haven, CT USA

[3] Dana Farber Canc Inst, Boston, MA USA

[4] Canc Inst Hosp JFCR, Canc Inst, Dept Adv Med Dev, Tokyo, Japan

[5] South Texas Accelerated Res Therapeut, San Antonio, TX USA

[6] NEXT Oncol, San Antonio, TX USA

[7] NEXT Oncol, San Antonio, TX USA

[8] Sarah Cannon Res Inst, Nashville, TN USA

[9] Tennessee Oncol PLLC, Tennessee Oncol, Nashville, TN USA

[10] Natl Canc Ctr Hosp East, Dept Med Oncol, Kashiwa, Japan

[11] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA

[12] Natl Canc Ctr, Dept Expt Therapeut, Tokyo, Japan

[13] Wakayama Med Univ Hosp, Dept Pulm Med & Med Oncol, Wakayama, Japan

[14] Virginia Canc Specialists VCS Res Inst, Fairfax, VA USA

[15] Showa Univ, Adv Canc Translat Res Inst, Tokyo, Japan

[16] Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Houston, TX 77030 USA

[17] START, Clin Res, San Antonio, TX USA

[18] Daiichi Sankyo Inc, Global Oncol Clin Dev, Basking Ridge, NJ USA

[19] Daiichi Sankyo Europe GmbH, Global Oncol Clin Dev, Munich, Germany

[20] Daiichi Sankyo Co Ltd, Data Intelligence, Tokyo, Japan

[21] Daiichi Sankyo Co Ltd, Global Oncol Clin Dev, Tokyo, Japan

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2024年 / 42卷 / 19期

关键词：

GUIDELINE; INHIBITOR;

D O I：

10.1200/JCO.23.01909

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSEDatopotamab 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 METHODSTROPION-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.RESULTSAt 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.CONCLUSIONIn 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.

引用

页码：2281 / 2294

页数：17

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