Investigational Drug
Giredestrant
TrialFetch AI Analysis
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Overview
Giredestrant (GDC-9545) is an investigational oral treatment studied for estrogen receptor–positive (ER-positive), HER2-negative breast cancer. Randomized trials have reported results in both early and advanced disease; the findings differ by treatment setting. (sabcs.org)
Mechanism of action
Giredestrant is a selective estrogen receptor degrader (SERD). It binds to and antagonizes the estrogen receptor and promotes its degradation, aiming to suppress the signaling that drives ER-positive tumors. (pubmed.ncbi.nlm.nih.gov)
Efficacy
- Early breast cancer (phase III lidERA): After a median 32.3 months of follow-up, three-year invasive disease-free survival was 92.4% with adjuvant giredestrant versus 89.6% with standard endocrine therapy (hazard ratio 0.70; p=0.0014). An overall-survival benefit had not been established at this interim analysis. (sabcs.org)
- Previously treated advanced breast cancer (phase III evERA): Giredestrant plus everolimus improved median progression-free survival to 8.77 months, versus 5.49 months with standard endocrine therapy plus everolimus (hazard ratio 0.56). Among patients with a detectable ESR1 mutation, the corresponding figures were 9.99 versus 5.45 months. (annalsofoncology.org)
- First-line advanced breast cancer (phase III persevERA): Giredestrant plus palbociclib did not meet the trial’s threshold for a statistically significant progression-free-survival improvement over letrozole plus palbociclib: median 33.1 versus 28.2 months (hazard ratio 0.89; p=0.1553). Objective response rates were 60.2% versus 58.8%. (asco.org)
- Earlier phase II evidence: In previously treated advanced disease, acelERA reported objective response rates of 13% with giredestrant versus 7% with physician-selected endocrine therapy, but did not meet its primary progression-free-survival endpoint. In the preoperative coopERA study, giredestrant suppressed the tumor-proliferation marker Ki67 more than anastrozole after two weeks; later response rates with palbociclib were similar (50% versus 49%). (aacrjournals.org)
Safety
In lidERA, the most commonly reported adverse events with giredestrant were joint pain (48.0%), hot flushes (27.4%) and headache (15.3%); 5.3% discontinued because of adverse events, versus 8.2% on standard endocrine therapy. In evERA, common events with giredestrant plus everolimus included mouth inflammation (47.3%), diarrhea (26.9%) and anemia (23.6%); 8.2% discontinued because of adverse events, versus 6.5% in the comparator arm. These combination-trial events cannot necessarily be attributed to giredestrant alone. (sabcs.org)
Further reading
- lidERA phase III conference abstract
- evERA phase III conference abstract
- persevERA phase III conference abstract
- coopERA phase II peer-reviewed article
Last updated: Sep 2026
Active trials using Giredestrant
Found 5 active trials using this drug:
TrialFetch AI summary: For patients with locally advanced or metastatic ER-positive, HER2-negative breast cancer that progressed during or after CDK4/6 inhibitor therapy, this study evaluates oral GDC-0587, a selective CDK4 inhibitor, alone or with giredestrant, an estrogen receptor degrader.
ClinicalTrials.gov ID: NCT07214662
TrialFetch AI summary: Adults with locally advanced or metastatic ER-positive, HER2-negative breast cancer that progressed on or after CDK4/6 inhibitor and endocrine therapy, and who have not received chemotherapy for metastatic disease, receive investigational GDC-4198 alone or with giredestrant in dose finding. The randomized comparison tests two doses of GDC-4198, a CDK4/CDK2 inhibitor, plus giredestrant, an oral estrogen receptor degrader, against abemaciclib plus giredestrant.
ClinicalTrials.gov ID: NCT07100106
TrialFetch AI summary: For patients with incurable locally advanced or metastatic ER-positive, HER2-negative breast cancer who relapse during or within 12 months after adjuvant endocrine therapy and have received no systemic treatment for advanced disease. Patients receive giredestrant, an investigational oral selective estrogen receptor degrader, or fulvestrant, each combined with a CDK4/6 inhibitor; efficacy is assessed overall and by ESR1 mutation status.
ClinicalTrials.gov ID: NCT06065748
TrialFetch AI summary: Patients with measurable recurrent or persistent endometrial carcinoma after 1–2 prior systemic therapies are assigned to biomarker-matched cohorts. Open cohorts evaluate atezolizumab (anti–PD-L1) plus talazoparib (PARP inhibitor) for high genomic loss of heterozygosity or tiragolumab (anti-TIGIT) for MSI-high/high-TMB tumors, and inavolisib (PI3Kα inhibitor) plus letrozole for PIK3CA-mutant tumors or giredestrant (ER degrader) plus abemaciclib (CDK4/6 inhibitor) for RB1-intact, low-grade ER-positive tumors.
ClinicalTrials.gov ID: NCT04486352
TrialFetch AI summary: For patients with inoperable locally advanced or metastatic ER-positive breast cancer, treatment cohorts include HER2-negative disease after CDK4/6 inhibitor–containing endocrine therapy, HER2-positive disease after trastuzumab–taxane and HER2-directed therapy, and HER2-negative, PIK3CA-mutated disease recurring during or shortly after adjuvant endocrine therapy. Arms test giredestrant, an investigational oral estrogen receptor degrader, alone or with CDK4/6, PI3K, AKT, mTOR, or CDK7 inhibitors, atezolizumab, and/or pertuzumab–trastuzumab, depending on cohort.
ClinicalTrials.gov ID: NCT04802759
