giredestrant (RG6171) / Roche - LARVOL DELTA

Preoperative window-of-opportunity study with giredestrant or tamoxifen (tam) in premenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) and Ki67≥10% early breast cancer (EBC): The EMPRESS study (ESMO 2025) - P2 | "Additional endpoints will be reported at the meeting. Conclusions Giredestrant, administered without LHRH analogs, demonstrated superior antiproliferative activity than tam in terms of Ki67 reduction in premenopausal women with ER+/HER2- EBC."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Giredestrant (GIRE), an oral selective oestrogen receptor (ER) antagonist and degrader, + everolimus (E) in patients (pts) with ER-positive, HER2-negative advanced breast cancer (ER+, HER2– aBC) previously treated with a CDK4/6 inhibitor (i): Primary results of the phase III evERA BC trial (ESMO 2025) - P3 | "Randomisation was 1:1 to once-daily oral 30 mg GIRE + 10 mg E or SOC ET (exemestane/fulvestrant/tamoxifen) + E until PD or unacceptable toxicity. The safety profile of GIRE + E was manageable with no unexpected findings. GIRE + E may represent a new effective treatment option in the post-CDK4/6i setting."

Clinical • Late-breaking abstract • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

Giredestrant vs standard-of-care endocrine therapy as adjuvant treatment for patients with estrogen receptor-positive, HER2-negative early breast cancer: Results from the global Phase III lidERA Breast Cancer trial (SABCS 2025) - P3 | "Giredestrant, a next-generation oral selective estrogen receptor antagonist and degrader (SERD), was shown to be more potent than other SERDs (Liang 2021; Bardia 2023) and demonstrated superior antiproliferative activity vs anastrozole in the neoadj coopERA BC trial (Hurvitz 2023)... Pts with Stage I-III ER+ HER2- eBC were randomized 1:1 to giredestrant 30 mg oral daily (with an LHRH agonist in pre- and peri-menopausal women, and men) or standard-of-care ET (tamoxifen or aromatase inhibitor) for 5 years (yr)... lidERA BC is the first Phase III trial to demonstrate benefit with an oral SERD in eBC. Giredestrant tx resulted in a statistically significant and clinically meaningful IDFS improvement vs standard-of-care ET in ER+, HER2- eBC. OS trended in favor of the giredestrant arm, and DRFI was improved vs standard-of-care ET."

Clinical • P3 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Clinical and biomarker subgroup analysis of evERA Breast Cancer: A Phase III trial of giredestrant plus everolimus in patients with estrogen receptor-positive, HER2-negative advanced breast cancer previously treated with a CDK4/6 inhibitor (SABCS 2025) - P3 | "Methods Pts who had ER+, HER2- aBC with disease progression (PD) post-CDK4/6i + ET in the aBC setting, or relapse during/after CDK4/6i + ET in the adjuvant setting, were randomized 1:1 to once-daily oral 30 mg GIRE + 10 mg E or SOC ET (exemestane, fulvestrant, or tamoxifen) + E until PD or unacceptable toxicity. Conclusions GIRE + E led to clinically meaningful improvements in INV-PFS vs SOC ET + E irrespective of PIK3CAm and PIK3CA/AKT1/PTEN alt, and other key relevant subgroups, regardless of ESR1m status. These data support the use of GIRE + E vs SOC ET + E in pts with ER+, HER2- aBC post-CDK4/6i + ET."

Biomarker • Clinical • Metastases • P3 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA • PTEN

PREcoopERA: A Window-of-Opportunity Trial of Giredestrant +/- Triptorelin vs. Anastrozole + Triptorelin in Premenopausal Patients With ER-positive/HER2-negative Early Breast Cancer (clinicaltrials.gov) - P2 | N=231 | Completed | Sponsor: ETOP IBCSG Partners Foundation | Recruiting ➔ Completed | Trial completion date: Jun 2026 ➔ Sep 2025 | Trial primary completion date: Jun 2026 ➔ Sep 2025

Trial completion • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Primary results from the phase 2 endomERA study of giredestrant for patients with grade 1 endometrioid endometrial cancer (SGO 2026) - No abstract available

Clinical • P2 data • Endometrial Cancer • Oncology • Solid Tumor

Giredestrant, an oral selective estrogen receptor degrader, is central to its oncology portfolio. With pivotal data from the persevERA trial anticipated in 2026, the company prepares for potential global regulatory submissions. (GeneOnline) - "GlobalData projections indicate potential annual sales of $1.7 billion by 2031, though competition from AstraZeneca’s Camizestrant and Olema Pharmaceuticals’ Palazestrant is significant. Roche is also exploring combination approaches with Itovebi, GDC-4198, and ZN-1041 to differentiate its clinical outcomes. Ten pivotal Phase III readouts are expected in 2026, including the persevERA trial, which may influence Roche’s competitive position in the market."

Commercial • P3 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-0587 as a Monotherapy and in Combination With Giredestrant in Participants With Locally Advanced or Metastatic Estrogen Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer (clinicaltrials.gov) - P1 | N=136 | Recruiting | Sponsor: Genentech, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • First-in-human • Monotherapy • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Selective Estrogen Receptor Degraders Induce Bradycardia by Modulating Nuclear Estrogen Signaling. (PubMed, JACC Basic Transl Sci) - "Giredestrant and camizestrant induced significant bradycardia in wild-type zebrafish embryos, whereas fulvestrant and amcenestrant (SERDs that do not induce bradycardia in patients) did not alter heart rate. Mutations in gper, esr2a, and esr2b did not confer resistance to SERD-induced bradycardia, whereas esr1 mutant embryos were protected. These findings demonstrate that SERD-associated bradycardia is mediated through Esr1 signaling, supporting an on-target adverse effect."

Journal • Breast Cancer • Cardiovascular • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER

Giredestrant (GDC-9545) vs physician choice of endocrine monotherapy (PCET) in patients (pts) with ER+, HER2– locally advanced/metastatic breast cancer (LA/mBC): Primary analysis of the phase II, randomised, open-label acelERA BC study (ESMO 2022) - P2 | "Giredestrant, a highly potent, non-steroidal, oral selective ER antagonist and degrader (SERD), achieves robust ER occupancy and was well tolerated and active as a single agent and in combination with palbociclib, regardless of ESR1 mutation, in phase I/II studies...Methods Post- and pre-/peri-menopausal women, or men, ≥18 years with measurable disease or evaluable bone lesions, who progressed after 1–2 lines of systemic therapy (≤1 targeted, ≤1 chemotherapy regimen, prior fulvestrant allowed) were randomised 1:1 to giredestrant (30 mg PO QD) or fulvestrant/aromatase inhibitor per local guidelines (+LHRH agonist in pre-/peri-menopausal women, and men) until disease progression/unacceptable toxicity...Giredestrant was well tolerated, with a safety profile comparable to PCET and consistent with known ET risks. Giredestrant continues to be investigated in other studies."

Clinical • Monotherapy • P2 data • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • ER • HER-2

lidERA breast cancer: A phase III adjuvant study of giredestrant (GDC-9545) vs physician’s choice of endocrine therapy in patients with estrogen receptor+, HER2– early breast cancer (SABCS 2022) - P3 | "It has been demonstrated to be more potent in vitro and achieves higher ER occupancy in vivo than fulvestrant, the only currently approved SERD...Pts are randomized 1:1 to oral 30 mg daily giredestrant or PCET (tamoxifen, anastrozole, letrozole, or exemestane, given according to prescribing information)...AB, PS and CG contributed equally. This abstract was originally presented at SABCS 2021 (OT2-11-09)."

Clinical • P3 data • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Exploratory subgroup and biomarker analyses of acelERA Breast Cancer: Phase II study of giredestrant (GDC-9545) vs physician’s choice of endocrine therapy for previously treated, estrogen receptor+, HER2– advanced breast cancer (SABCS 2022) - P2 | "METHODS Patients were post- and pre- or peri-menopausal women, or men, with ER+, HER2– aBC who had progressed after 1–2 lines of systemic therapy in the advanced setting (≤1 targeted agent; ≤1 chemotherapy regimen; prior fulvestrant allowed). Overall, these data support continued investigation of giredestrant to advance and improve treatment outcomes in hormone receptor+ BC. Exploratory subgroup analyses"

Biomarker • P2 data • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

Neoadjuvant palbociclib plus either giredestrant or anastrozole in oestrogen receptor-positive, HER2-negative, early breast cancer (coopERA Breast Cancer): an open-label, randomised, controlled, phase 2 study. (PubMed, Lancet Oncol) - P2 | "Giredestrant offers encouraging anti-proliferative and anti-tumour activity and was well tolerated, both as a single agent and in combination with palbociclib. Results justify further investigation in ongoing trials."

Journal • P2 data • Breast Cancer • Cardiovascular • Estrogen Receptor Positive Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Myocardial Infarction • Neutropenia • Oncology • Solid Tumor • ER • HER-2 • PGR

Giredestrant for Estrogen Receptor-Positive, HER2-Negative, Previously Treated Advanced Breast Cancer: Results From the Randomized, Phase II acelERA Breast Cancer Study. (PubMed, J Clin Oncol) - P2 | "Although the acelERA BC study did not reach statistical significance for its primary INV-PFS end point, there was a consistent treatment effect with giredestrant across most key subgroups and a trend toward favorable benefit among patients with ESR1-mutated tumors. Giredestrant was well tolerated, with a safety profile comparable to PCET and consistent with known endocrine therapy risks. Overall, these data support the continued investigation of giredestrant in other studies."

Journal • Metastases • P2 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

A window-of-opportunity (WOO) trial of giredestrant +/- LHRHa vs anastrozole+LHRHa in premenopausal women with ER+/HER2- early breast cancer (EBC) (IBCSG 67-22; PREcoopERA) (ESMO-BC 2024) - P2 | "Background Adjuvant endocrine therapy (ET) for premenopausal women with ER+/HER2- EBC often includes ovarian function suppression (OFS) via a GnRH or LHRH agonist (LHRHa) plus an aromatase inhibitor (AI) or tamoxifen...Trial design PREcoopERA is a randomized, open-label, 3-arm, WOO trial evaluating the anti-proliferative activity and safety of the oral SERD giredestrant +/- LHRHa triptorelin, as compared to the AI anastrozole + triptorelin...The first woman was enrolled on 25 January 2024. The PREcoopERA trial is sponsored and coordinated by ETOP IBCSG PartnersFoundation in collaboration with F. Hoffmann-La Roche Ltd."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Interim analysis (IA) of the giredestrant (G) + samuraciclib (SAMURA) arm in MORPHEUS breast cancer (BC): A phase I/II study of G treatment (tx) combinations in patients (pts) with oestrogen receptor-positive (ER+), HER2-negative, locally advanced/metastatic BC (LA/mBC) (ESMO 2024) - P1/2 | "Circulating tumour DNA was used to define genetic alterations. As of 16 October 2023, 18 and 15 pts were enrolled in the G and G + SAMURA arms, respectively; all had ECOG PS 0–1, 66.7% and 33.3% had prior fulvestrant and 72.2% and 46.7% (capped at 7 pts in the G + SAMURA arm) had liver metastasis at enrolment. Safety of G + SAMURA was aligned with the individual safety profile of each drug, with no overlapping toxicities or new safety signals. Updated data, including efficacy and biomarkers, will be presented."

Clinical • Metastases • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK7 • ER • HER-2

MiRaDoR: A PoC Study to Evaluate Treatments' Efficacy by Monitoring MRD Using ctDNA in HR-positive/HER2-negative EBC Population (clinicaltrials.gov) - P2 | N=1260 | Recruiting | Sponsor: MedSIR | Active, not recruiting ➔ Recruiting

Circulating tumor DNA • Enrollment open • Minimal residual disease • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

MORPHEUS BC: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer (clinicaltrials.gov) - P1/2 | N=316 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Nov 2027 ➔ May 2029 | Trial primary completion date: Nov 2027 ➔ May 2029

Trial completion date • Trial primary completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER

Giredestrant Delivers Long-Sought Adjuvant Benefit. (PubMed, Cancer Discov) - "The oral selective estrogen receptor degrader giredestrant prolonged invasive disease-free survival more than standard endocrine therapies, such as tamoxifen, letrozole, anastrozole, and exemestane, in the phase III lidERA study. Despite the lack of comparisons between the drug and CDK4/6 inhibitors and concerns over its potential cost, researchers were excited by the data, noting that it's the first improvement in adjuvant endocrine therapy in two decades."

Journal • ER

The use of oral selective estrogen receptor degraders (SERDs) by community-based general medical oncologists (GMOs) in ER-positive (ER+), HER2-negative (HER2-neg) metastatic breast cancer (mBC): A clinician survey of practice patterns and practical challenges (SABCS 2025) - "The 1/2023 approval of elacestrant (E) for patients with mBC and an ESR1 mutation (ESR1mut) whose disease progresses on endocrine therapy (ET) introduced new treatment considerations into a clinical situation which already had multiple approved therapeutic options...Regarding select other oral SERDs (imlunestrant, camizestrant, giredestrant), 46% of GMOs believe data are not sufficient to determine comparative efficacy...In terms of novel SERDs, many GMOs consider the newly approved imlunestrant equivalent to E and would consider its use with abemaciclib in certain circumstances. While GMOs are generally familiar with the key datasets, they are also highly motivated to learn more. GMOs have rapidly incorporated E into the management of progressive ER+ HER2-neg ESR1mut mBC. Similarities and differences in practice patterns were observed between GMOs and breast cancer research leaders (data available separately) for a number of clinical situations surveyed."

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

Giredestrant immobilizes the Estrogen Receptor to potently suppress ER-active breast cancers (SABCS 2025) - "In particular, orally bioavailable selective ER antagonists and degraders (SERDs) were designed to overcome exposure limitations of fulvestrant and achieve deep and sustained ER inhibition, to both treat and delay resistance. Rather, the limited gains observed for novel SERDs in 2/3L ESR1 wildtype mBC is more likely a function of tumor biology, whereby those tumors tend to be ER activity-low, a context in which differentiation of endocrine therapies is challenging. Advances delivered by latest-generation SERDs may be more apparent where ER activity is more consistently high; a number of ongoing clinical trials, including those in earlier treatment lines, will test this hypothesis."

Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CRBN • ER

Giredestrant/Everolimus Improves PFS Across Subgroups After CDK4/6i in ER+/HER2- Breast Cancer (Targeted Oncology) - "...Findings presented at the 2025 San Antonio Breast Cancer Symposium....In those with both ESR1 and PIK3CA mutations, the HR favoring giredestrant plus everolimus was 0.38 (95% CI, 0.20–0.69) whereas it was 0.54 (95% CI, 0.36–0.83) for those with PIK3CA mutations in the ITT population. Among patients with ESR1 mutations but no detectable PIK3CA mutation, the HR for giredestrant plus everolimus was 0.47 (95% CI, 0.31–0.70), compared with 0.59 (95% CI, 0.45–0.79) in the ITT population. For individuals with PIK3CA/AKT1/PTEN alterations, the HR was 0.45 (95% CI, 0.27–0.76) in the ESR1-mutant cohort and 0.54 (95% CI, 0.38–0.77) in the ITT population."

P3 data • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Giredestrant: "With a median follow-up of 32.3 months, the lidERA trial demonstrated a statistically significant and clinically meaningful improvement with upfront giredestrant over standard-of-care ET in ER+, HER2-negative, Stage I-III eBC"; Breast cancer (Roche) - SABCS 2025: "IDFS hazard ratio: 0.70 (95% CI: 0.57, 0.87; p = 0.0014); 3-year IDFS rates: 92.4% vs 89.6%."

P3 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Oncology

Giredestrant: Data from P3 heredERA trial (NCT05296798) for locally advanced or metastatic breast cancer in 2027 (Roche) - SABCS 2025

P3 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Oncology

Giredestrant: Regulatory submissions in US/EU for post CDKi ER+/HER2- metastatic breast cancer (in combination with everolimus) in 2026 (Roche) - SABCS 2025: Regulatory approval in US for post CDKi ER+/HER2- metastatic breast cancer (in combination with everolimus) in 2026

EMA filing • FDA filing • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Oncology