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

Author(s): Aditya Bardia, MD, PhD¹; Ian E. Krop, MD, PhD^2,3; Takahiro Kogawa, MD, PhD⁴; Dejan Juric, MD¹; Anthony W. Tolcher, MD^5,6,7; Erika P. Hamilton, MD^8,9; Toru Mukohara, MD, DMedSci¹⁰; Aaron Lisberg, MD¹¹; Toshio Shimizu, MD, PhD^12,13; Alexander I. Spira, MD¹⁴; Junji Tsurutani, MD, PhD¹; Senthil Damodaran, MD, PhD¹⁵; Kyriakos P. Papadopoulos, MD¹⁶; Jonathan Greenberg, MD, MA, BA^17,18; Fumiaki Kobayashi, PhD, MS²²; Hong Zebger-Gong, MD, PhD¹⁸; Rie Wong, BS²⁰; Yui Kawasaki, PhD¹⁷; Tadakatsu Nakamura, MS¹⁹; Funda Meric-Bernstam, MD¹⁵

Source: https://doi.org/10.1200/JCO.23.01909

Dr. Anjan Patel's Thoughts

Datopotamab Deruxtecan is a new ADC that will likely be approved in the near future. The payload is the same as used in Enhertu, but the antibody is directed at TROP2. This report is from the TROPION-pan tumor study and shows a promising ORR in HR+/HER2- MBC. There is reasonable data for this compound in 2L met-NSCLC in the TROPION-LUNG01 study with an improvement in PFS compared to docetaxel of 4.4 vs 3.7 months. Dato also is effective in patients with actionable genetic alterations in the 2L setting. There is also an ongoing study on its use in the 1L setting for met-NSCLC in combination with pembrolizumab and chemotherapy.

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.

Author Affiliations

¹Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA; ²Yale Cancer Center, New Haven, CT; ³Dana-Farber Cancer Institute, Boston, MA; ⁴Department of Advanced Medical Development, Cancer Institute Hospital of JFCR, Tokyo, Japan; ⁵South Texas Accelerated Research Therapeutics, San Antonio, TX; ⁶NEXT Oncology, San Antonio, TX; ⁷Texas Oncology, San Antonio, TX; ⁸Sarah Cannon Research Institute, Nashville, TN; ⁹Tennessee Oncology, PLLC, Nashville, TN; ¹⁰Department of Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan; ¹¹Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA; ¹²Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan; ¹³Department of Pulmonary Medicine and Medical Oncology, Wakayama Medical University Hospital, Wakayama, Japan; ¹⁴Virginia Cancer Specialists (VCS) Research Institute, Fairfax, VA; ¹⁵Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX; ¹⁶Clinical Research, START, San Antonio, TX; ¹⁷Global Oncology Clinical Development, Daiichi Sankyo, Inc, Basking Ridge, NJ; ¹⁸Global Oncology Clinical Development, Daiichi Sankyo Europe GmbH, Munich, Germany; ¹⁹Data Intelligence, Daiichi Sankyo, Co, Ltd, Tokyo, Japan; ²⁰Global Oncology Clinical Development, Daiichi Sankyo, Co, Ltd, Tokyo, Japan

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