58P - Safety and pharmacokinetics (PK) of vepdegestrant in Japanese patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)- advanced breast cancer: Results from a Japanese phase I study

Background

Vepdegestrant (ARV-471) is an oral PROteolysis TArgeting Chimera (PROTAC) ER degrader. Based on results of the phase 2 cohort expansion (VERITAC) of a phase 1/2 study (NCT04072952), vepdegestrant 200 mg once daily (QD) was selected as the recommended phase 3 dose (RP3D). This phase 1 study (NCT05463952) investigated the safety, PK, and preliminary efficacy of vepdegestrant in Japanese patients with ER+/HER2- advanced breast cancer at the RP3D.

Methods

Patients with ER+/HER2- advanced breast cancer who were resistant to standard therapy or for whom no standard therapy was available or who had received ≥2 prior endocrine therapies in any setting were eligible. Vepdegestrant 200 mg was given QD with food. The primary endpoint was dose-limiting toxicities (DLTs) in cycle 1; secondary endpoints included safety, PK, and antitumor activity.

Results

Six female patients were treated; median age was 58 years (range: 47–62). Five patients received ≥3 prior regimens for advanced disease; 5 patients received prior CDK4/6 inhibitors. At the data cutoff (May 4, 2023), median treatment duration was 9.8 weeks (range: 6–28); 2 patients remained on treatment. No DLTs were observed. Four (66.7%) patients experienced adverse events (AEs); none led to dose reduction or discontinuation. Treatment-related AEs were abdominal discomfort, anemia, dizziness, increased alanine aminotransferase, increased aspartate aminotransferase, nausea, and pruritus (1 event each); all were grade 1 except anemia (grade 2). Geometric mean C_max and AUC₂₄ 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 patients demonstrated stable disease at week 24 assessment.

Conclusions

The RP3D of vepdegestrant 200 mg QD was well tolerated in Japanese patients with ER+/HER2- advanced breast cancer. Vepdegestrant will be evaluated in 2 global, randomized phase 3 studies in patients with ER+/HER2- advanced breast cancer: as second/third-line monotherapy in VERITAC-2 (NCT05654623) and as first-line therapy in combination with palbociclib in VERITAC-3 (NCT05909397).

Clinical trial identification

NCT05463952.

Editorial acknowledgement

Editorial support provided by Nathan Yardley, PhD, and Melissa Austin of Apollo Medical Communications, part of Helios Global Group, and funded by Arvinas Operations, Inc.

Legal entity responsible for the study

Pfizer, Inc.

Funding

Pfizer, Inc.

Disclosure

H. Iwata: Financial Interests, Personal, Advisory Board: Chugai, Daiichi Sankyo, AstraZeneca, Lilly, Sanofi; Financial Interests, Personal, Invited Speaker: Chugai, Daiichi Sankyo, AstraZeneca, Lilly, Pfizer, Sanofi, Taiho; Financial Interests, Personal and Institutional, Steering Committee Member: Chugai, Daiichi Sankyo, AstraZeneca, MSD, Amgen, Sanofi, Novartis, Pfizer, Kyowa Hakko Kirin; Financial Interests, Personal and Institutional, Local PI: Lilly, Bayer, Behringer, Nihon Kayaku. Y. Naito: Financial Interests, Personal, Invited Speaker, Speakers Bureau: Chugai, Pfizer, Eli Lilly, Eisai, AstraZeneca, PDR pharma, Novartis, Gardant, Ono, Takeda, Taiho, Bayer, Nihon Kayaku, Daiichi Sankyo, Bristol, MSD; Financial Interests, Personal, Funding: Roche; Financial Interests, Personal, Local PI: AbbVie, Boehringer Ingelheim, Ono, Chugai, Taiho, Pfizer, AstraZeneca, Gilead, Takeda; Financial Interests, Personal, Steering Committee Member: Daiichi Sankyo; Non-Financial Interests, Personal, Principal Investigator, JCOG: Natera. M. Hattori: Financial Interests, Personal, Speaker’s Bureau: Pfizer. K. Yonemori: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, Sanofi, Genmab, Gliad, OncoXerna, Takeda, Novartis, MSD; Financial Interests, Personal, Invited Speaker: Pfizer, Eisai, AstraZeneca, Eli Lilly, Takeda, Chugai, Fuji Film Pharma, PDR Pharma, MSD, Ono, BMS, Boeringer Ingerheim, Daiichi Sankyo, Bayer, Jansen, Sanofi; Financial Interests, Institutional, Local PI: MSD, Daiichi Sankyo, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seagen, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirrin, Nihon Kayaku, Haihe. M. Aizawa, J. Yoshimitsu: Financial Interests, Personal, Full or part-time Employment: Pfizer R&D Japan. Y. Mori, Y. Umeyama: Financial Interests, Personal, Full or part-time Employment: Pfizer R&D Japan; Financial Interests, Personal, Stocks/Shares: Pfizer Inc. T. Mukohara: Financial Interests, Personal, Research Grant: Daiichi Sankyo, Sysmex, Eisai, MSD, Pfizer, Novartis, Sanofi, Chugai, AstraZeneca, Ono; Financial Interests, Personal, Speaker, Consultant, Advisor, Lecture fees: Eisai, Pfizer, Novartis, Chugai, Eli Lilly, AstraZeneca, Kyowa-Kirin, Taiho. All other authors have declared no conflicts of interest.