In a patient with estrogen receptor (ER)-positive, HER2-negative breast cancer, neoadjuvant treatment with (Z)-endoxifen in combination with exemestane plus goserelin has been dosed for the first time, signaling the start of the phase 2 EVANGELINE (NCT05607004) trial.1
The selective estrogen receptor modulator therapy, (Z)-endoxifen, is an anti-estrogen metabolite of tamoxifen, according to the developer, Atossa Therapeutics, Inc. The agent works by binding to and interfering with protein kinase C beta 1 function.
Trial Name: A Randomized Phase 2 Non-inferiority Trial of (Z)-Endoxifen and Exemestane + Goserelin as Neoadjuvant Treatment in Premenopausal Women With ER+/HER2- Breast Cancer
ClinicalTrials.gov Identifier: NCT05607004
Sponsor: Atossa Therapeutics, Inc.
Recruitment Contacts: Heather Fraser, PhD, 206-707-3088, email@example.com or Melinda M. Bomar, firstname.lastname@example.org
Completion Date: July 2025
Previously in a phase 2 study, (Z)-endoxifen achieved a 65.1% reduction in Ki-67. This type of response could aid in improving 5-year disease-free survival for ER-positive, HER2-negative breast cancer. Prior research also shows that (Z)-endoxifen monotherapy can deter ovarian function suppression in premenopausal women, as well as decrease cancer cell proliferation.
"This study is looking to determine if Z-endoxifen (study drug) can treat premenopausal women's breast cancer without the need for injections for ovarian suppression or surgery to remove the ovaries. Results of the study may lead to less patient's having side effects from long term hormone suppression, John G. Knecht III, MD, director of CLS Health Oncolog, and associate professor of Medicine at UTMB Health told Targeted OncologyTM.
EVANGELINE is a multicenter, open-label study. Approximately 174 patients will be included in the study and will be randomized 1:1 to receive the combination of (Z)-endoxifen 20mg-80mg with exemestane, and goserelin or exemestane plus goserelin alone.2
The primary end point of the study is to determine the (Z)-endoxifen steady-state plasma concentration of eligible patients who complete at least 1 cycle of treatment. As a coprimary end point, the study will assess endocrine sensitive disease rate based on Ki-67 percent after 4 weeks of treatment.
The secondary end points of the study include other pharmacokinetic measures, the incidence of adverse events (AEs), serious AEs, and AEs leading to discontinuation, as well as the percentage of patients whose serum TK1 falls below the detection limit at 4 weeks, overall response rate, pathologic complete response rate, rate of preoperative endocrine prognostic index at time of surgery, class of residual cancer burden at time of surgery, conversion rate, actual conversion rate, change from pre-neoadjuvant treatment in E1 and E2, and change from pre-neoadjuvant treatment in cholesterol levels.
Patients are eligible to enroll given they are premenopausal women aged 18 years or older who are not lactating, pregnant, or planning pregnancy. All patients must agree to use contraception. Patients are also required to have ER-positive, HER2-negative disease with ER ≥ 67%, clinical stage IIA or IIB invasive breast cancer, be Nottingham grade 1 or 2, have a tumor diameter > 2.0, and have an ECOG performance status of 0 to 2.
The study excludes individuals who have inflammatory breast cancer, or prior diagnosis or treatment for breast cancer.Patients with uncontrolled illnesses like hypertension and diabetes, and several other comorbidities are no eligible to enroll. The study also excludes patients with inadequate laboratory values as baseline, those previously treatment with hormonal therapies, and those allergic to any medications that will be used in the study.
“We are excited to kick-off this important trial, a significant achievement in our development strategy,” said Steven Quay, MD, PhD, the president and chief executive officer of Atossa Therapeutics, Inc, in a press release. “Approximately 78% of breast cancers are ER+/HER2- and premenopausal women diagnosed with this disease need more effective and tolerable treatment options; specifically new treatments that do not require ovarian function suppression. We feel (Z)-endoxifen has the potential to change the treatment paradigm for these patients.”
1. Atossa doses first patient in phase 2 neoadjuvant clinical study of (z)-endoxifen in premenopausal women with ER+/HER2- breast cancer. News release. Atossa Therapeutics, Inc. February 23, 2023. Accessed February 23, 2023. https://bit.ly/3IyKTsS
2. (Z)-Endoxifen for the treatment of premenopausal women with ER+/HER2- breast cancer (EVANGELINE). ClinicalTrials.gov. Updated February 6, 2023. Accessed February 23, 2023. https://clinicaltrials.gov/ct2/show/NCT05607004?term=EVANGELINE&draw=2&rank=1