Trial to Test (Z)-endoxifen, Verzenio in ER+, HER2- Breast Cancer

A clinical trial will evaluate (Z)-endoxifen plus Verzenio (abemaciclib) for the treatment of women with estrogen receptor (ER)-positive, HER2-negative breast cancer, according to a press release from Atossa Therapeutics and Quantum Leap Healthcare Collaborative.

Study researchers are planning on enrolling approximately 20 patients to participate in the I-SPY 2 Endocrine Optimization Protocol (EOP). All patients will receive 40 mg of (Z)-endoxifen and 150 mg of Verzenio each day for 24 weeks leading up to surgery.

(Z)-endoxifen is a type of endocrine therapy called a selective estrogen receptor modulator (SERM) that, according to breastcancer.org, works by blocking the body’s estrogen from binding with cancer cells. More specifically, (Z)-endoxifen targets PKCβ1, which is a known protein associated with cancer.

Verzenio works by blocking the CDK4/6 proteins that — similarly to estrogen — are involved in the growth and reproduction of cancer.

“Endocrine therapy in combination with CDK 4/6 inhibition is a widely used treatment for patients with advanced-stage ER+ breast cancer and as an adjuvant [post-surgical] therapy for node positive, hormone-positive early-stage disease, found at the time of surgical resection,” Dr. Laura Esserman, director of the University of California San Francisco Breast Care Center and founder of Quantum Leap Healthcare Collaborative, said in a press release.

About I-SPY 2 EOP

The I-SPY 2 EOP will include patients with newly diagnosed ER-positive invasive breast cancer whose tumors are predicted to respond to endocrine (hormonal) therapy, but who may derive little or no response from chemotherapy. According to the press release, this group of patients is at high risk of recurrence after five years, and new treatments are needed for this population.

“Women with high clinical stage but less proliferative tumors (molecularly low risk or those with late recurrence risk) are challenging to treat. Late recurrence is high regardless of either endocrine or chemotherapy. Thus, we are looking for new combined treatments, which can be used in the pre-surgery (neoadjuvant) setting. We look forward to learning more about the potential of (Z)-endoxifen in combination with [Verzenio] in the neoadjuvant setting in the I-SPY TRIAL,” Esserman said.

Prior research has also showed that (Z)-endoxifen showed promise in ER-positive breast cancer.

“Data recently presented at the American Association for Cancer Research (AACR) annual meeting was extremely encouraging as it shows that (Z)-endoxifen can not only stop ER-positive breast cancer from growing, but it can also shrink or eliminate the tumor, as measured by MRI imaging,” said Dr. Steven Quay, Atossa’s president and chief executive officer, in the release. “Combining this activity with a targeted therapy like CDK 4/6 inhibition, which interrupts the process through which breast cancer cells divide and multiply, has the potential to deliver efficacy beyond the sum of the two monotherapies. We look forward to seeing the results of this study as it will help us better understand which patients are best suited for mono versus combination therapy in the neoadjuvant setting. It will also inform plans to potentially explore this combination in the advanced-stage and metastatic breast cancer settings.”

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