The first participant has been enrolled in a Phase 2 clinical trial evaluating the safety and efficacy of GDC-9545 in combination with palbociclib as an investigational treatment for postmenopausal women with estrogen receptor (ER)-positive and HER2-negative untreated early breast cancer.

“The initiation of enrolment is an important milestone as we aim to better understand the activity and safety of this therapy in early stage breast cancer,” Sara Hurvitz, MD, medical director of the Jonsson Comprehensive Cancer Center Clinical Research Unit, in Canada, and the study’s principal investigator, said in a press release.

The growth of some breast cancers is driven by the hormone estrogen, with such tumors said to be ER-positive. Blocking estrogen signaling can be an effective treatment strategy for such tumors.

“Although we have effective therapies for hormone receptor positive breast cancer, disease resistance to these therapies occurs in some women, leading to the diagnosis of incurable breast cancer sometimes years later,” Hurvitz said.

GDC-9545 is an estrogen receptor degrader — it binds to the protein receptor for the estrogen hormone, causing this receptor to be destroyed, and thereby reducing estrogen signaling.

The investigational compound was found to be well-tolerated and to have promising tumor activity, both alone and in combination with palbociclib in ER-positive metastatic breast cancer patients.

Now, researchers will test the compound in early stage breast cancer. The new Phase 2 clinical trial (NCT04436744), sponsored by Roche, seeks to enroll approximately 215 postmenopausal women with early ER-positive, HER2-negative breast cancer. Of note, HER2 is another protein receptor that drives the growth of some cancers.

The study is recruiting participants at several locations in the U.S, many of them in California. Additional information on locations and contacts can be found here.

Participants will be randomly assigned to one of two treatment groups: a GDC-9545 group or an anastrozole group. Anastrozole is an approved, non-steroidal aromatase inhibitor, a type of breast cancer treatment that works by reducing levels of estrogen in the body. Notably, both GDC-9545 and anastrozole are intended to limit estrogen signaling, albeit through different mechanisms.

The trial is open-label, meaning participants will know which medication they are being given.

For the first two weeks of treatment, participants will be given either GDC-9545 or anastrozole alone, taken by mouth once daily. Then, the participants will continue taking their respective medication while they also undergo four 28-day treatment cycles with palbociclib. An approved treatment for ER-positive breast cancer, palbociclib works by interfering with molecular signals that trigger cell growth in cancer cells.

After these treatments, the women will undergo surgery.

The main goal of the trial is to determine the effect of treatment alone, specifically after the first two weeks, on cancer cell growth. This will be determined by examining the expression of Ki67, a marker of cell growth, on biopsies.

The trial also will assess how many participants respond to treatment, how much GDC-9545 is present in the blood, and various safety-related endpoints or goals.

“Innovative therapies, such as GDC9545, will hopefully be shown to improve outcomes for women,” Hurvitz said.

“My team and I are anxious to explore the use of this investigational therapy in the context of a presurgical trial, where the tumor may be sampled prior to and after treatment is given,” she said. “Our hope is that we will not only learn about this drug’s anti-tumor activity but will also be able to identify what makes some tumors sensitive and others resistant to this form of therapy.”