Roche's Next-Gen Oral SERD Giredestrant Shows Significant Tumor Proliferation Suppression in Neoadjuvant Treatment of ER+/HER2- Postmenopausal Early Breast Cancer

September 20, 2021 /BioonBIOON/ -- Roche recently at the 2021 European MedicalTumorThe randomized phase II coopERA trial was presented at the ESMO virtual congress.Breast cancerInterim data from the trial. The trial is evaluatingNext-Generation Oral Selective Estrogen Receptor Degrader (SERD) Giredestrant (Formerly GDC-9545) for Neoadjuvant Treatment of Postmenopausal Patients with ER-Positive, HER2-Negative Early Breast Cancer (eBC).

The results show: during the window of opportunity 14 days after treatment,Compared with anastrozole, giredestrant treatment showed Ki67 (a measure ofTumorprognostic markers of proliferation) decreased (respectively: 80% vs 67%, p=0.0222). The safety profile of giredestrant was consistent with previous trials, with fewer patients experiencing adverse events associated with giredestrant and anastrozole.

Dr. Levi Garraway, Chief Medical Officer and Head of Global Product Development at Roche, stated: “We are pleased to share the first randomized Phase 2 data for giredestrant, showing: giredestrant demonstrates encouraging activity and safety in patients with early-stage HR-positive, HER2-negative breast cancer. Our ongoing comprehensive HR-positive breast cancer program aims to address significant unmet needs among patient populations whose quality of life continues to be profoundly impacted, including the risks of resistance and disease recurrence.”

Giredestrant is an oral, next-generation SERD designed to completely block ER signaling, demonstrating high receptor occupancy and a distinctive preclinical profile.Estrogen promotes the growth of HR-positive breast cancer cells by binding to the ER. Giredestrant blocks the effects of estrogen by blocking this receptor and induces receptor degradation in the process. InClinical TrialIn China, giredestrant has demonstrated efficacy regardless of ESR1 mutation status (ESR1 gene mutations are a key mechanism of resistance to endocrine therapy).

December 2020, United StatesFDAFast Track Designation (FTD) has been granted to giredestrant for the treatment of ER-positive, HER2-negative, second- and third-line metastatic breast cancer. Administered orally, giredestrant has demonstrated encouraging clinical efficacy and safety, and exhibited superior potency compared to other SERDs in preclinical studies. Oral giredestrant has the potential to transform the patient treatment experience, offering a therapeutic option with greater convenience and less discomfort compared to intramuscular injection therapies.

Interim analysis data from 83 of 202 patients enrolled in the coopERA breast cancer study indicate that, compared with anastrozole, giredestrant demonstrates superior antiproliferative activity and a favorable safety profile in HR-positive, HER2-negative breast cancer:

During the window-of-opportunity period (Days 1–14) of this neoadjuvant (preoperative) study, the relative reduction in Ki67 was used as a proliferation biomarker to assess the pharmacodynamic effects of giredestrant, which indicates the treatment's ability to inhibit tumor growth: (1)Giredestrant resulted in a mean Ki-67 reduction of 80% (95% CI: -85%, -72%), whereas anastrozole resulted in a mean Ki-67 reduction of 67% (95% CI: -75%, -56%), p = 0.0222.。（2）Consistent Ki67 inhibition with giredestrant treatment was observed in patients with baseline Ki67 ≥20% or baseline Ki67 <20% (baseline Ki67 ≥20% population: 83% vs 71%; baseline Ki67 <20% population: 65% vs 24%).。（3）After 14 days of treatment, 25% of patients in the giredestrant treatment group# Tumorshowed a complete cell cycle arrest rate (CCCA) of 5% for anastrozole (Δ20%; 95% CI: -37% to -3%)The safety profile of giredestrant is consistent with its mechanism of action. Giredestrant-related adverse effects (28%) were less frequent than those associated with anastrozole (38%). No grade ≥3 adverse events (AEs) or serious adverse events related to giredestrant occurred. (Bioon.com)

Original Source:Roche presents first phase II data on giredestrant, a next generation selective oestrogen receptor degrader, in untreated oestrogen receptor (ER)-positive, early breast cancer