FDA Okays Initiation of Endoxifen Study in Ovarian Cancer

A patient with ovarian cancer has begun treatment with oral endoxifen, an active metabolite of tamoxifen, after a Safe to Proceed Letter was granted by the FDA, according to a press release by Atossa Therapeutics, Inc.¹

Tamoxifen is an FDA-approved drug to treat ovarian and breast cancer. In order to work, tamoxifen must be broken down by the liver into active compounds known as metabolites. The most active metabolite is endoxifen. Third-party clinical studies have found that the use of Z-endoxifen resulted in robust antitumor and antiestrogenic activity in endocrine-sensitive and letrozole-resistant breast tumors when compared to tamoxifen and aromatase inhibitor monotherapy.¹

So far, 5 clinical studies of endoxifen have been completed, inducing expanded access to a study of a female breast cancer patient who has been taking oral endoxifen for over 2 years with no recurrence to date.¹

Under the FDA’s Safe to Proceed Letter, the use of endoxifen for ovarian cancer is restricted to this one patient.¹

The patient also underwent genomic testing. Laboratory growths revealed the optimal drug combination for tumor response was endoxifen and alpelisib (Piqray). Alpelisib was approved by the FDA in 2019 for the use in combination with endocrine therapy fulvestrant for the treatment of postmenopausal women, and med, with HER2-negative PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen.

Endoxifen has shown clinical promise in breast cancer. A phase 2 study of endoxifen was halted early due to substantially positive results.² During the study, 7 patients with newly diagnosed ER+ and HER2- stage 1 or 2 invasive breast cancer requiring mastectomy or lumpectomy received oral endoxifen for at least 14 days from the time of diagnosis up to the day of surgery.

The primary endpoint of the study was to determine if the administration of oral Endoxifen reduces tumor activity as measured by Ki-67. Secondary endpoints included safety and tolerability. Ki-67, a standard measurement of breast cancer cell proliferation is an important biomarker for care providers and patients as low Ki-67 is associated with a lower risk of death from breast cancer. 

Interim results of the study found that Ki-67 was reported by more than 50% in every patient in the widow of opportunity between biopsy and surgery. This amounted to an overall reduction of 74%. After treatment, all patients had a Ki-67 below 25. No safety or tolerability issues were reported. This includes vasomotor symptoms that are often associated with tamoxifen such as hot flashes and night sweats.

“The patient has recurrent ovarian cancer and did not tolerate tamoxifen, which is sometimes prescribed for ovarian cancer as well as breast cancer,” said Steven Quay, MD, PhD, Atossa’s president and chief executive officer, in a press release. “The patient recently underwent functional molecular genomic testing using 3D tumor organoid cultures grown in the laboratory from the patient’s tumor to help determine potential therapies. This testing revealed that the combination of endoxifen and alpelisib produced an exceptional tumor response. We will follow the progress of this patient and consider additional clinical studies in patients with ovarian cancer.”¹

_REFERENCE:

_{1.Atossa Therapeutics’ phase 2 Endoxifen breast cancer study produces substantially positive results allowing study to be halted early. News release. Atossa. February 2, 2021. Accessed April 9, 2021. https://bit.ly/3wHFnwZ.} 

_{2.Atossa Therapeutics announces ovarian cancer patient has begun treatment with oral Endoxifen under FDA’s expanded access pathway. Press release. Atossa. April 8, 2021. Accessed April 9, 2021. https://bit.ly/39Yxg5L.}