Safety and pharmacokinetics of vepdegestrant in Japanese patients with ER+ advanced breast cancer: a phase 1 study

Hiroji Iwata; Yoichi Naito; Masaya Hattori; Akiyo Yoshimura; Kan Yonemori; Mana Aizawa; Yuko Mori; Junichiro Yoshimitsu; Yoshiko Umeyama; Toru Mukohara

doi:10.1007/s10147-024-02648-3

Safety and pharmacokinetics of vepdegestrant in Japanese patients with ER+ advanced breast cancer: a phase 1 study

Int J Clin Oncol. 2024 Nov 20. doi: 10.1007/s10147-024-02648-3. Online ahead of print.

Authors

Hiroji Iwata^{1

2}, Yoichi Naito³, Masaya Hattori⁴, Akiyo Yoshimura⁴, Kan Yonemori⁵, Mana Aizawa⁶, Yuko Mori⁷, Junichiro Yoshimitsu⁷, Yoshiko Umeyama⁷, Toru Mukohara³

Affiliations

¹ Department of Breast Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan. hiwata0422@gmail.com.
² Core Laboratory, Graduate School of Medical Sciences, Department of Medical Research and Developmental Strategy, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. hiwata0422@gmail.com.
³ Department of Medical Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
⁴ Department of Breast Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan.
⁵ Department of Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji Chuo-ku, Tokyo, 104-0045, Japan.
⁶ Department of Biometrics and Data Management, Pfizer R&D Japan, 3-22-7 Yoyogi, Shibuya-ku, Tokyo, 151-8589, Japan.
⁷ Department of Clinical Research, Pfizer R&D Japan, 3-22-7 Yoyogi, Shibuya-ku, Tokyo, 151-8589, Japan.

PMID: 39565495
DOI: 10.1007/s10147-024-02648-3

Abstract

Background: Vepdegestrant (ARV-471) is an oral PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader.

Methods: This phase 1 study (NCT05463952) investigated safety, pharmacokinetics, and antitumor activity of vepdegestrant in Japanese patients with ER-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer at the 200-mg once daily (QD) recommended phase 3 dose. Eligible patients had ER+/HER2- advanced breast cancer resistant to standard therapy, with no standard therapy available, or had received two or more prior endocrine therapies in any setting. The primary endpoint was dose-limiting toxicities (DLTs) in cycle 1; secondary endpoints included safety, pharmacokinetics, and antitumor activity.

Results: Six female patients (median age, 58 [range: 47-62] years) were treated. For advanced disease, three (50.0%) patients received three or more prior regimens and five (83.3%) patients received prior cyclin-dependent kinase 4/6 inhibitors. At data cutoff, median treatment duration was 9.8 (range: 6-28) weeks; two patients remained on treatment. No DLTs were observed. Four (66.7%) patients experienced adverse events; none led to dose reduction or discontinuation. Four (66.7%) patients had treatment-related adverse events; all were grade 1 except anemia (grade 2). Geometric mean maximum plasma concentration and 24-h area under the plasma concentration-time curve of vepdegestrant were 630.9 ng/mL and 10,400 ng∙hr/mL after a single dose and 1056 ng/mL and 18,310 ng∙hr/mL after multiple doses. Two (33.3%) patients demonstrated stable disease at week 24.

Conclusion: Vepdegestrant 200 mg QD was well tolerated in Japanese patients with ER+/HER2- advanced breast cancer with no notable differences in pharmacokinetics from Western patients.

Clinical trial registration: ClinicalTrials.gov: NCT05463952 (date of registration: July 19, 2022).

Keywords: Advanced breast cancer; Estrogen receptor–positive; Human epidermal growth factor receptor 2–negative; Japanese patients; Safety; Vepdegestrant.

Associated data

ClinicalTrials.gov/NCT05463952