Patritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3–Directed Antibody-Drug Conjugate, in Patients With Previously Treated Human Epidermal Growth Factor Receptor 3–Expressing Metastatic Breast Cancer: A Multicenter, Phase I/II Trial

Author:

Krop Ian E.1ORCID,Masuda Norikazu2ORCID,Mukohara Toru3ORCID,Takahashi Shunji4ORCID,Nakayama Takahiro5,Inoue Kenichi6ORCID,Iwata Hiroji7ORCID,Yamamoto Yutaka8ORCID,Alvarez Ricardo H.9,Toyama Tatsuya10,Takahashi Masato11ORCID,Osaki Akihiko12,Saji Shigehira13ORCID,Sagara Yasuaki14ORCID,O'Shaughnessy Joyce15,Ohwada Shoichi16,Koyama Kumiko16,Inoue Tatsuya17,Li Li18,Patel Parul18,Mostillo Joseph18,Tanaka Yoshimi18,Sternberg David W.18,Sellami Dalila18,Yonemori Kan19ORCID

Affiliation:

1. Yale Cancer Center, New Haven, CT

2. Nagoya University Graduate School of Medicine, Nagoya, Japan

3. National Cancer Center East, Kashiwa, Japan

4. The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan

5. Osaka International Cancer Institute, Osaka, Japan

6. Saitama Cancer Center, Saitama, Japan

7. Aichi Cancer Center Hospital, Nagoya, Japan

8. Kumamoto University Hospital, Kumamoto, Japan

9. Southeastern Regional Medical Center, Newnan, GA

10. Nagoya City University, Nagoya, Japan

11. Department of Breast Surgery, Hokkaido University Hospital, Sapporo, Japan

12. Saitama Medical University International Medical Center, Hidaka, Japan

13. Fukushima Medical University Hospital, Fukushima, Japan

14. Hakuaikai Social Medical Corporation, Sagara Hospital, Kagoshima, Japan

15. Baylor University Medical Center, Texas Oncology, Dallas, TX

16. Daiichi Sankyo Co, Ltd, Tokyo, Japan

17. Daiichi Sankyo RD Novare Co, Ltd, Tokyo, Japan

18. Daiichi Sankyo, Inc, Basking Ridge, NJ

19. National Cancer Center Hospital, Tokyo, Japan

Abstract

PURPOSE Human epidermal growth factor receptor 3 (HER3) is broadly expressed in breast cancer; high expression is associated with an adverse prognosis. Patritumab deruxtecan (HER3-DXd) is an investigational HER3-targeted antibody-drug conjugate that is being evaluated as a novel treatment in HER3-expressing advanced breast cancer in the U31402-A-J101 study. METHODS Adults with disease progression on previous therapies were eligible. Patients in the dose-escalation, dose-finding, and dose-expansion parts received HER3-DXd 1.6-8.0 mg/kg intravenously once every 3 weeks or one of two alternative dosing regimens. In the dose-escalation part, the primary objectives were to determine the maximum tolerated dose and recommended dose for expansion (RDE). The safety and efficacy of the RDE were assessed during dose expansion. RESULTS One hundred eighty-two enrolled patients received ≥1 dose of HER3-DXd. Patients had a median of five previous therapies for advanced disease. Efficacy results are reported across clinical subtypes: hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-negative) breast cancer (n = 113; objective response rate [ORR], 30.1%; median progression-free survival [mPFS], 7.4 months), triple-negative breast cancer (n = 53; ORR, 22.6%; mPFS, 5.5 months), and HER2-positive breast cancer (n = 14; ORR, 42.9%; mPFS, 11.0 months). Objective responses were observed in cancers with HER3-high and HER3-low membrane expression. Dose-limiting toxicities observed during dose selection were decreased platelet count and elevated aminotransferases. In dose expansion, GI and hematologic toxicities were the most common treatment-emergent adverse events (TEAEs) observed. Grade ≥3 TEAEs were observed in 71.4% of patients, and 9.9% discontinued treatment because of TEAEs. Three grade 3 and one grade 5 treatment-related interstitial lung disease events occurred. CONCLUSION HER3-DXd demonstrated a manageable safety profile and durable efficacy in heavily pretreated patients across clinical subtypes. These data warrant further evaluation of HER3-DXd in patients with HER3-expressing metastatic breast cancer.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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