Researchers are always seeking safer, more effective treatment options for breast cancer patients through clinical trials, with the hope that these new treatments could also be more tolerable. For people living with metastatic estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer, the hormone therapy fulvestrant is the standard treatment for those whose cancer has progressed on a combination of hormone therapy plus a CDK4/6 inhibitor as their initial treatment. 

Fulvestrant works well as a second-line treatment, as it has been the standard of care for many years, but it’s not perfect. As Virginia Borges, M.D., a medical oncologist at the University of Colorado observes, this treatment can also greatly impact a patient’s quality of life. 

“Fulvestrant is two big injections, once a month,” Dr. Borges says. “So, it has never been a particularly convenient drug for the person who has to have that happen on a monthly basis.” 

Dr. Borges doesn’t believe in settling for the status quo when it comes to treating breast cancer and is committed to finding more and better options for her patients.  

“We are never complacent when we have a drug that has demonstrated benefit and is FDA-approved,” she says. “We want to use science and chemistry and sophisticated drug design to say, ‘Okay, well this worked, but can we change the way it is affecting the cancer?’” 

Palazestrant and the OPERA-01 Clinical Trial 

Dr. Borges is an investigator for the OPERA-01 clinical trial. This is one of several phase 3 clinical trials aiming to bring the next generation of hormone therapies to patients with metastatic ER+/HER2- breast cancer. Phase 3 clinical trials compare new treatments with the best currently available treatment. The OPERA-01 clinical trial will compare the safety and effectiveness of an investigational hormone therapy, palazestrant (OP-1250), to fulvestrant. Palazestrant is being developed by Olema Oncology. 

OPERA-01 will compare factors between these two drugs including how long patients stay on the treatment without their cancer getting worse (called progression-free survival), overall survival, how well the cancer responds to the treatment, general safety and how patients feel during their treatment.  

In July 2022, the U.S. FDA granted Fast-Track designation to Olema Oncology for the development of palazestrant. Through a fast track, the FDA can help expedite the review of a drug to help treat serious medical conditions and fulfill an unmet need. 

A New Treatment Approach 

In early tests, palazestrant has shown promise in patients who have already tried many treatments, with manageable side effects and good results. Palazestrant is both a complete estrogen receptor antagonist (a next-generation CERAN) and a selective estrogen receptor degrader (SERD).  

As Dr. Borges explains, palazestrant is building on the success of fulvestrant. 

“Think of the estrogen receptor as almost a small little Lego set, and different pieces have to come together for it to have its action,” Dr. Borges explains. “Fulvestrant binds to the estrogen receptor in one place and causes it to break apart. The Lego block breaks into a bunch of pieces, so it can’t tell cancer cells to keep growing and spreading.” 

In comparison, palazestrant blocks the estrogen receptor and the signals it sends, while also helping break down the estrogen receptor. OPERA-01 researchers hope this more complete approach will make this treatment work even better and last longer than the standard of care. 

“Palazestrant binds in two places in the estrogen receptor, so in theory, that’s going to do a better job of causing the estrogen receptor to break apart and stop working,” Dr. Borges explains. 

Benefits to Having More Tools in the Toolbox 

OPERA-01 is one of many clinical trials building upon past discoveries to improve progression-free survival for people with metastatic ER+/HER2- breast cancer. As Dr. Borges explains, the goal is to ensure these patients run the longest “race” possible. 

“You might think you’re signed up for the marathon and we want you doing the Iron Man, and living as long as possible with this disease,” she says. “In the treatment of ER+ breast cancer, my patient is now running an ultramarathon they didn’t sign up for. We need many, many supports along the way to get them through that ultramarathon and the bottom line is, the longer the ultramarathon, the better.” 

Patients with metastatic ER+/HER2- breast cancer need additional treatment options that work better and are more tolerable. Thankfully, researchers are working tirelessly to find more options for these patients. 

“We want more tools in the toolbox,” Dr. Borges says. “Every single drug that we bring to market that can improve the duration of progression-free survival means that patients are living longer. And that’s the goal ‒ getting them to have as many years as possible.” 

Learn more about the OPERA-01 trial. 

Visit our clinical trials page to learn more about clinical trials and read about our other featured clinical trials.  

Did you know? Komen has invested in more than 700 new discoveries and over 400 potential treatments in the research pipeline for MBC. 

Trial Fact Sheet

Olema Oncology is a sponsor for the Spotlight on Clinical Trials series and the sponsor of OPERA-01.