Comparing a New Drug, Palazestrant, to Standard Treatment for Advanced Breast Cancer

About the Study

This study is testing palazestrant (also called OP-1250), an investigational medicine, for people with estrogen receptor-positive (ER-positive), HER2-negative advanced or metastatic breast cancer. The study compares palazestrant to standard endocrine (hormone) therapy options: fulvestrant or an aromatase inhibitor (anastrozole, letrozole, or exemestane). People may be able to join if their cancer has grown or returned after one or two prior endocrine therapy treatments for advanced breast cancer, including a treatment that combined endocrine therapy with a CDK4/6 inhibitor. Researchers will track how long treatment can keep the cancer from getting worse, along with side effects and other outcomes.

What the Study Involves

People will be randomly assigned (by chance) to one of two groups. You and the study team will know which treatment you are getting (this is an open-label study). 

Group 1: Experimental drug: Palazestrant (OP-1250)

• Palazestrant is taken by mouth once a day in 4-week (28-day) treatment cycles.
• In one part of the study, two dose levels are being evaluated (90 mg or 120 mg once daily). In the main part of the study, participants receive palazestrant at the dose chosen from that evaluation.

Group 2: Standard Hormone Therapy

• The study doctor will choose one of these standard endocrine (hormone) therapies:
  • Fulvestrant: injections on Day 1 and Day 15 of the first 4-week (28-day) cycle, then on Day 1 of each cycle after that
  • Anastrozole: tablets taken once a day in 4-week (28-day) cycles
  • Letrozole: tablets taken once a day in 4-week (28-day) cycles
  • Exemestane: tablets taken once a day in 4-week (28-day) cycles

Adults (18 years and older) may be able to join if they meet the main requirements below. The study team will review the full list with each person.

• ER-positive, HER2-negative breast cancer that is locally advanced or metastatic and is not expected to be cured with standard treatments
• People whose cancer can be seen or tracked by doctors (on scans or in the bones)
• Previously treated for advanced breast cancer with endocrine therapy combined with a CDK4/6 inhibitor
• May have had one additional endocrine therapy by itself. The most recent endocrine therapy must have been taken for at least 6 months.
• Able to carry out normal daily activities (ECOG performance status 0 or 1)
• People with healthy blood counts and organ function (liver and kidneys)
• People who have not gone through menopause (or are close to menopause) must be willing to take medicine to lower estrogen levels during the study (a GnRH/LHRH agonist)

• People whose cancer is causing serious symptoms in major organs or is at risk of causing organ failure
• People who have received chemotherapy for breast cancer in the advanced/metastatic setting
• People who have previously been treated with elacestrant or a similar experimental hormone-targeting therapy
• People who have had an allergic reaction to any of the study treatments
• People who cannot safely take standard hormone therapy based on medical guidance
• People whose cancer has spread to the brain or spinal cord and is causing symptoms that need immediate treatment