Endoxifen Showcases Antitumor Activity in Breast Cancer, Phase 2 Trial Halted

February 3, 2021 - Oral endoxifen, when delivered during the “window of opportunity” between diagnosis of breast cancer and surgery, resulted in a 74% average reduction in Ki-67 and Ki-67 levels lower than 25% at the time of surgery.

Oral endoxifen, when delivered during the “window of opportunity” between diagnosis of breast cancer and surgery, resulted in a 74% average reduction in Ki-67 and Ki-67 levels lower than 25% at the time of surgery, according to data from the first 6 patients enrolled in an Australian phase 2 trial, which has since been halted due to the positive results.1

“It is a welcome event to halt an ongoing clinical trial because the results are so overwhelmingly positive,” Steven Quay, MD, PhD, president and chief executive officer of Atossa Therapeutics, Inc., stated in a press release. “Data from the first 6 patients…[showed that at] the time of surgery all patients had Ki-67 levels lower than 25%, which is an important threshold to improve long-term survival as identified in studies by others. We believe that additional enrollment will not alter these positive results, so we are terminating the study early.”

The goal of adjuvant therapy for patients with nonmetastatic breast cancer who have undergone surgery is to reduce the risk of disease recurrence.2 Giving treatment during the “window of opportunity” before surgery also possesses the potential to reduce the risk of recurrence, although the chief goal of neoadjuvant treatment is to downstage the tumor and learn more about tumor response. Downstaging tumors could become operable.

In the open-label phase 2 trial, investigators set out to determine whether endoxifen results in a reduction in tumor cell proliferation, as measured by biomarkers like Ki-67, in patients with estrogen receptor­–positive, HER2-negative, stage I or II invasive breast cancer; these patients had disease that was in need of a mastectomy or lumpectomy. The trial was designed to conduct an interim analysis evaluating change in Ki-67. To be successful, a meaningful change in Ki-67 had to be experienced by 2 of 8 patients.

In the trial, patients were given endoxifen for at least 14 days from diagnosis to surgery. Key secondary end points of the trial focused on safety and tolerability. Investigators also evaluated drug expression levels on estrogen and progesterone receptors.

Earlier results from the trial showed that endoxifen resulted in a 74% reduction in tumor cell proliferation over 22 days of dosing; this was determined to be statistically significant (P = .031). At this time, 6 patients had reported a significant reduction in Ki-67. In every patient who received endoxifen in the “window of opportunity”, Ki-67 was reduced by over 50%. Following treatment, participants had a Ki-67 that was less than 25%.

No safety and tolerability issues were observed with endoxifen.

These data proved to be consistent with data that had read out from an expanded-access, single-patient study that evaluated the oral agent. In 2018, the FDA gave the green light to a single-patient, investigational new drug application for 1 patient with breast cancer to receive the agent during the “window of opportunity.” After receiving endoxifen on a daily basis for the duration of 20 days before undergoing surgery, the patient had a 50% reduction in Ki-67. These findings led to another compassionate use approval from the regulatory agency for the same patient, who received endoxifen as an adjuvant treatment for longer than 1 year.


  1. Atossa Therapeutics’ phase 2 endoxifen breast cancer study produces substantially positive results allowing study to be halted early. News release. Atossa Therapeutics, Inc. February 2, 2021. Accessed February 2, 2021. http://bit.ly/3atfKpx.
  2. Atossa Therapeutics announces positive interim phase 2 data from endoxifen breast cancer treatment. News release. Atossa Therapeutics, Inc. May 7, 2020. Accessed February 2, 2021. http://bit.ly/3tjHsO1.