What question did this study set out to answer?

This trial investigates the effectiveness of (Z)-endoxifen with goserelin to suppress tumor proliferation in women with ER+/HER2– breast cancer.

May 30, 2026

A phase 2 clinical trial in progress of (Z)-endoxifen plus goserelin as neoadjuvant therapy in premenopausal women with ER+/HER2– breast cancer (EVANGELINE).

Key Points

This trial investigates the effectiveness of (Z)-endoxifen with goserelin to suppress tumor proliferation in women with ER+/HER2– breast cancer.
Phase 2, open-label, multicenter clinical trial (NCT05607004).
Daily 40 mg endoxifen plus goserelin administered every 28 days in premenopausal women with ER+/HER2– breast cancer.
A Simon two-stage design enrolling 20 patients in the first stage, followed by another 25 if initial results are promising.
Primary endpoint aims for at least 65% of patients with Ki-67 >10% achieving Ki-67 ≤10% after 4 weeks of therapy.
A parallel cohort of 20 patients is assessed for overall response rate at 24 weeks per RECIST v1.1.
Secondary objectives include evaluating safety, tolerability, and various cancer burden metrics.

Abstract

TPS655 Background: Early (14-28 day) on-treatment suppression of tumor proliferation during neoadjuvant endocrine therapy (NET) is strongly associated with favorable long-term outcomes in estrogen receptor–positive (ER+) HER2– breast cancer. In premenopausal women, tamoxifen with or without ovarian function suppression (OFS) results in suboptimal Ki-67 suppression compared with aromatase inhibitor + OFS. (Z)-endoxifen (ENDX), the active metabolite of tamoxifen, dually inhibits ER signaling and PKCβ1-mediated AKT activation, supporting its evaluation as an alternative NET strategy in this population. Methods: EVANGELINE (NCT05607004) is an ongoing, multicenter, open-label Phase 2 study evaluating daily 40 mg ENDX plus goserelin administered every 28 days as neoadjuvant therapy in premenopausal women with ER+/HER2–, cT2–3, cN0–1 breast cancer. The primary objective is to determine the proportion of patients with baseline Ki-67 >10% who achieve Ki-67 ≤10% after 4 weeks of therapy. A Simon two-stage design is used to test whether the Week 4 Ki-67 ≤10% rate is at least 65%, with 20 patients enrolled into the first stage and, if promising, another 25 patients enrolled into the second stage (cohort A). A parallel cohort of 20 patients with baseline Ki-67 ≤10% (cohort B) is enrolled to assess objective response rate (ORR) at 24 weeks per RECIST v1.1. Secondary objectives include examining safety and tolerability, residual cancer burden, and PEPI score. Correlative analyses include examining effect of treatment on select tumor and plasma biomarkers. Clinical trial information: NCT05607004 .

Ask AI

Helpful

Bookmark