What Is Giredestrant?
Giredestrant is an investigational drug currently being studied for various types of cancer. It is classified as a highly potent, non-steroidal, oral selective estrogen receptor antagonist and degrader, often referred to as a SERD. This means giredestrant works by blocking the activity of estrogen receptors and causing their breakdown within cancer cells. By doing so, it aims to stop the growth of cancers that rely on estrogen to thrive.
Clinical trials for giredestrant began on April 16, 2019, with the latest trial projected to conclude on April 21, 2026. To date, 19 clinical trials have been conducted or are ongoing, involving a total of 10,847 participants. These studies are primarily sponsored by Hoffmann-La Roche and Genentech, Inc., alongside other organizations like MedSIR and Alliance Foundation Trials, LLC.
Uses and Conditions Under Study
Giredestrant is primarily being investigated as a treatment for various forms of breast cancer. Many of these trials focus on estrogen receptor-positive (ER-positive), HER2-negative breast cancer, including locally advanced or metastatic stages, and early breast cancer. In these types of breast cancer, cancer cells have estrogen receptors that can be stimulated by estrogen, leading to tumor growth. As a selective estrogen receptor degrader (SERD), giredestrant aims to block and degrade these receptors, thereby inhibiting cancer cell growth. A total of 16 trials are exploring giredestrant for different breast cancer indications, including early breast cancer and ER-positive, HER2-negative metastatic breast cancer.
Beyond breast cancer, giredestrant is also being studied for other hormone-sensitive cancers. There are two trials investigating its potential use in endometrial cancer, a type of cancer that begins in the lining of the uterus. Additionally, one trial is exploring giredestrant for ovarian cancer. These studies aim to determine if giredestrant's mechanism of action, by targeting estrogen receptors, could also be beneficial in managing these other gynecological cancers.
Dosing
Giredestrant is administered orally, meaning it is taken by mouth. While specific dosage forms like tablets or capsules are not detailed, the oral administration suggests a solid oral formulation. Clinical trials have investigated several strengths of giredestrant, including 10 mg, 30 mg, and 100 mg doses.
The most frequently studied dose mentioned in trial descriptions is 30 mg, taken once daily. For example, some studies involve participants receiving giredestrant at a dose of 30 mg orally once daily on Days 1-28 of each 28-day cycle. Treatment duration can vary, with some protocols specifying up to 4.5 years or until disease recurrence or unacceptable toxicity. Other studies describe administration from day 1 until the day of re-biopsy or surgery, or for a total of 24 weeks (6 cycles) in the absence of disease progression or unacceptable toxicity before surgery. All reported dosing regimens are for adult patients.
Side Effects
In a study (NCT04436744) evaluating Giredestrant plus palbociclib compared to anastrozole plus palbociclib, approximately 34.7% of participants receiving Giredestrant plus palbociclib experienced at least one adverse event, compared to 32.7% of participants receiving anastrozole plus palbociclib.
In another study (NCT03916744) of Giredestrant as a single agent, all 53 participants experienced at least one adverse event. Specific types of adverse events and their frequencies were not detailed in the provided data for this study. However, broad categories of abnormalities were observed:
- Abnormal vital signs were reported in 86.5% of participants.
- Abnormalities in blood chemistry and coagulation tests occurred in up to 25.0% of participants who did not have the abnormality at baseline.
- Abnormalities in hematology tests were observed in up to 8.5% of participants who did not have the abnormality at baseline.
- Abnormal electrocardiogram (ECG) parameters were noted in 5.3% of participants.
Clinical Trial Results
Clinical trials have investigated Giredestrant in postmenopausal and premenopausal women with estrogen receptor-positive (ER+), HER2-negative breast cancer across different stages.
Early Breast Cancer (Monotherapy)
In a study (NCT03916744) involving postmenopausal women with Stage I-III operable, ER+ breast cancer, Giredestrant monotherapy demonstrated an impact on tumor cell proliferation. On average, the proportion of Ki67-positive nuclei (a marker of cell proliferation) at surgery was reduced to 22% of the baseline level across all Giredestrant doses (10, 30, or 100 mg).
Early Breast Cancer (Combination Therapy)
The coopERA Breast Cancer study (NCT04436744) compared Giredestrant plus palbociclib to anastrozole plus palbociclib in postmenopausal women with ER+/HER2- untreated early breast cancer. Key findings included:
- The rate of complete cell cycle arrest (CCCA) at Week 2 was 19.6% for participants receiving Giredestrant plus palbociclib, compared to 12.8% for those on anastrozole plus palbociclib.
- Giredestrant plus palbociclib led to a greater reduction in Ki67 scores, with post-treatment Ki67 being 25% of baseline, compared to 33% for anastrozole plus palbociclib.
- The overall response rate (ORR) by ultrasound was similar between the two groups, with 50.0% for Giredestrant plus palbociclib and 49.1% for anastrozole plus palbociclib.
Locally Advanced or Metastatic Breast Cancer
The acelERA Breast Cancer study (NCT04576455) evaluated Giredestrant against physician's choice of endocrine monotherapy in participants with previously treated ER+/HER2- locally advanced or metastatic breast cancer. Results showed:
- The clinical benefit rate was 31.8% for Giredestrant, compared to 21.1% for physician's choice.
- The objective response rate was 12.6% for Giredestrant, versus 7.2% for physician's choice.
- Median progression-free survival (PFS) was 5.55 months for Giredestrant and 5.36 months for physician's choice.
- In participants with ESR1 gene mutations, Giredestrant showed a median PFS of 7.20 months, significantly longer than 3.48 months for physician's choice. For those with wild-type ESR1, physician's choice had a slightly longer median PFS (6.60 months) compared to Giredestrant (5.32 months).
- Median overall survival (OS) was 27.50 months for Giredestrant and 29.77 months for physician's choice.
Premenopausal Early Breast Cancer
A preoperative study (NCT05659563) in premenopausal women with ER+/HER2- and Ki67≥10% compared Giredestrant to tamoxifen. Key findings included:
- Giredest
Currently Recruiting Trials
Giredestrant is currently being investigated in several clinical trials for various forms of breast cancer and other conditions, often in combination with other targeted therapies. These studies aim to evaluate its safety and effectiveness, offering potential new treatment options for patients.
One Phase 1a/1b study, NCT07214662, sponsored by Genentech, Inc., is assessing GDC-0587 (a CDK4 inhibitor) as a standalone treatment and in combination with Giredestrant. This trial is enrolling up to 136 participants with locally advanced or metastatic estrogen receptor-positive and human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer.
Another Genentech, Inc. study, NCT07100106, is a Phase 1/2 trial comparing GDC-4198 alone and with Giredestrant against abemaciclib and Giredestrant. This study seeks to enroll up to 285 participants with locally advanced or metastatic ER+, HER2- breast cancer.
For patients with ER-positive, HER2-negative early breast cancer, Fondazione Oncotech is sponsoring NCT06259929, a Phase 2 study. This trial evaluates the efficacy and safety of abemaciclib and Giredestrant administered before surgery, with an enrollment target of 51 patients.
MedSIR is conducting NCT05708235, a Phase 2 study focused on monitoring minimal residual disease (MRD) using circulating tumor DNA (ctDNA). This trial involves Giredestrant alone or in combination with abemaciclib or inavolisib for 976 participants with HR-positive/HER2-negative early-stage breast cancer at higher risk of relapse.
A large Phase 3 study, NCT06065748, sponsored by Hoffmann-La Roche, is comparing Giredestrant combined with a CDK4/6 inhibitor against fulvestrant plus a CDK4/6 inhibitor. This trial is for 1050 participants with ER-positive, HER2-negative advanced breast cancer that has become resistant to adjuvant endocrine therapy.
Beyond breast cancer, Giredestrant is also being studied in NCT04486352, a Phase 1b/2 trial from Alliance Foundation Trials, LLC. This study is exploring Giredestrant in combination with abemaciclib for 148 participants with recurrent or persistent endometrial cancer.
Finally, Hoffmann-La Roche's NCT04802759 is a Phase 1b/2 umbrella study evaluating Giredestrant as a monotherapy and in numerous combinations with other agents like abemaciclib, inavolisib, and atezolizumab. This study aims to enroll 316 participants with inoperable, locally advanced or metastatic, ER-positive breast cancer.
Where to Participate
Clinical trials for Giredestrant are broadly accessible, with study sites located across the United States. There are currently 107 sites spread across 88 cities in 33 states, making participation possible for a wide range of patients.
Some of the top locations with multiple active sites include:
- Duarte, California
- Philadelphia, Pennsylvania
- Boston, Massachusetts
- Washington D.C., District of Columbia
- San Francisco, California
- Pittsburgh, Pennsylvania
- Atlanta, Georgia
- St Louis, Missouri
- St. Petersburg, Florida
- Nashville, Tennessee
Eligibility for these trials generally requires participants to be between 18 and 18 years of age. All genders are welcome, but these studies do not enroll healthy volunteers or children.
Development Timeline
The journey of Giredestrant in clinical development began on April 16, 2019, with its first clinical trial. Since then, the drug has been investigated in a total of 19 trials, enrolling over 10,847 participants.
Initially, Giredestrant was explored for conditions such as IBS-C and hyperphosphatemia. However, its development pipeline quickly expanded, with a strong focus emerging on various forms of breast cancer. This expansion included studies for Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer, Early-Onset Breast Cancer, and Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer. The drug's potential also led to investigations in Endometrial Cancer and Ovarian Cancer.
Hoffmann-La Roche and Genentech, Inc. have been the primary sponsors, driving the majority of these studies. The development has progressed through different phases, with eight Phase 2 trials and six Phase 3 trials currently underway, indicating significant advancement and a strong commitment to understanding Giredestrant's full therapeutic potential. The latest trial is projected to conclude by April 21, 2026.