giredestrant (RG6171) / Roche - LARVOL DELTA

Retrospective exploratory biomarker (BM) analyses from evERA Breast Cancer (BC): A Phase III trial of giredestrant (GIRE) + everolimus (E) in patients (pts) with oestrogen receptor-positive, HER2-negative advanced BC (ER+, HER2– aBC) in the post-CDK4/6 inhibitor (i) setting (ESMO 2026) - No abstract available

Biomarker • Metastases • P3 data • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Patient (pt)-reported outcomes (PROs) from the Phase III lidERA Breast Cancer (BC) trial of giredestrant (GIRE) in pts with oestrogen receptor-positive, HER2-negative early BC (ER+, HER2– eBC) (ESMO 2026) - No abstract available

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

Updated interim analysis of giredestrant (GIRE) + inavolisib (INAVO) in MORPHEUS Breast Cancer (BC): A Phase Ib/II study of GIRE treatment (tx) combinations in patients (pts) with oestrogen receptor-positive, HER2-negative locally advanced/metastatic BC (ER+, HER2– LA/mBC) (ESMO 2026) - No abstract available

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

MiRaDoR: A PoC Study to Evaluate Treatments' Efficacy by Monitoring MRD Using ctDNA in HR-positive/HER2-negative EBC Population (clinicaltrials.gov) - P2 | N=976 | Active, not recruiting | Sponsor: MedSIR | Recruiting ➔ Active, not recruiting

Circulating tumor DNA • Enrollment closed • Minimal residual disease • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • 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

Safety and patient (pt)-reported outcomes (PROs) from evERA breast cancer (BC): A phase III trial of giredestrant (GIRE) + everolimus (E) in pts with oestrogen receptor-positive, HER2-negative advanced BC (ER+, HER2- aBC) previously treated with a CDK4/6 inhibitor (i) (ESMO-BC 2026) - P3 | "We report efficacy/safety PROs and exploratory analyses of stomatitis (an E-associated adverse event [AE]) to further characterise the safety profile of GIRE + E. Pts were randomised 1:1 to once-daily oral 30 mg GIRE + 10 mg E or SOC ET (exemestane/fulvestrant/tamoxifen) + E. Dexamethasone mouthwash (MW; up to four times a day) was strongly recommended for stomatitis prophylaxis. These data further support the manageable safety and tolerability of GIRE + E. Pts with proactive MW prophylaxis had later onset and fewer G ≥ 2 E-associated stomatitis AEs. PROs support tx tolerability, showing maintained QoL, longer TTD in fn, longer time without pain worsening and no increase in tx burden from pts' perspective with GIRE + E."

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

Oral selective estrogen receptor degraders in ER+/HER2- breast cancer: a systematic review with pooled analysis of metastatic randomized trials and narrative synthesis of adjuvant evidence. (PubMed, Front Oncol) - "We searched PubMed, Cochrane CENTRAL, and conference abstract archives (SABCS, ESMO, ASCO; 2020-2026) for Phase II/III randomized controlled trials comparing oral SERDs (giredestrant, imlunestrant, elacestrant, camizestrant, vepdegestrant, amcenestrant) with standard endocrine therapy in ER-positive, HER2-negative breast cancer. This evidence synthesis across the full breast cancer continuum offers a framework for clinical decision-making as oral SERDs expand from advanced to early-stage disease. https://www.crd.york.ac.uk/prospero/display_record.php, identifier CRD420261358420."

Journal • Retrospective data • Review • 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 • Targeted Protein Degradation • ER • HER-2

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 (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

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

Giredestrant (GIRE) + palbociclib (PALBO) vs letrozole (LET) + PALBO as first-line (1L) therapy in patients (pts) with estrogen receptor–positive, HER2-negative locally advanced or metastatic breast cancer (ER+, HER2– LA/mBC): Primary analysis of the phase III persevERA BC trial. (ASCO 2026) - P3 | "GIRE, a next-generation oral selective full ER antagonist and degrader, has shown superior efficacy vs SOC ET in the adjuvant setting (lidERA BC; Bardia SABCS 2025) and in combination with everolimus vs SOC ET + everolimus in the post-CDK4/6i LA/mBC setting (evERA BC; Mayer ESMO 2025). 1L GIRE + PALBO resulted in a numerical improvement in INV-PFS vs LET + PALBO in ER+, HER2– LA/mBC, though it did not meet pre-defined statistical significance. The safety profile was tolerable, consistent with individual agents, with no unexpected findings. The ongoing 1L pionERA BC study (NCT06065748) is exploring GIRE vs fulvestrant, in combination with physician's choice of CDK4/6i in pts who have relapsed on adjuvant ET or with <12 mo TFI."

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

CO44657: A Study to Evaluate Efficacy and Safety of Giredestrant Compared With Fulvestrant (Plus a CDK4/6 Inhibitor), in Participants With ER-Positive, HER2-Negative Advanced Breast Cancer Resistant to Adjuvant Endocrine Therapy (pionERA Breast Cancer) (clinicaltrials.gov) - P3 | N=1050 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting | Trial primary completion date: Feb 2027 ➔ Apr 2028

Enrollment closed • Trial primary completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

Post-progression treatment (tx) analyses of evERA Breast Cancer (BC): A phase III trial of giredestrant (GIRE) + everolimus (E) in patients (pts) with estrogen receptor–positive, HER2-negative advanced BC (ER+, HER2– aBC) previously treated with a CDK4/6 inhibitor (i). (ASCO 2026) - P3 | " Pts with ER+, HER2– aBC who had disease progression (PD) or relapse during/post-CDK4/6i + ET were randomized 1:1 to once-daily oral 30 mg GIRE + 10 mg E or SOC ET (exemestane/ fulvestrant/tamoxifen) + E until PD/unacceptable toxicity. Delaying chemotherapy improves clinical and quality of life outcomes in ER+ aBC. These analyses further support the superior INV-PFS of GIRE + E over SOC ET + E observed in all pts and in the ESR1m population. Improvements in PFS2 and CFS, regardless of ESR1m status, suggest that the clinical benefit of GIRE + E is sustained beyond initial progression."

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

A window-of-opportunity (WOO) trial of giredestrant +/- LHRH analogue vs anastrozole + LHRHa in premenopausal patients with ER+/HER2- early breast cancer: PREcoopERA (ESMO-BC 2026) - P2 | "Pts were randomized to 28 days of: G (30 mg daily); GT (Triptorelin 3.75 mg IM D1), or AT (1 mg daily) with tumor re-biopsy on D29. GT and G showed robust anti-proliferative activity, though GT superiority to AT was not demonstrated. G was not non-inferior to GT, suggesting OFS remains relevant to optimal anti-proliferative effect. Regimens were well tolerated."

Clinical • Late-breaking abstract • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • ER • HER-2

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

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

EndomERA: A Study of Giredestrant in Participants With Grade 1 Endometrial Cancer (clinicaltrials.gov) - P2 | N=33 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed

Trial completion • Endometrial Cancer • Oncology • Solid Tumor • CD4

kalitERA: A Study to Learn How Well Participants With a Specific Type of Early Breast Cancer (ER-Positive, HER2-Negative) Tolerate and Stay on Treatment With Giredestrant and How They Feel During Treatment (clinicaltrials.gov) - P3 | N=1500 | Not yet recruiting | Sponsor: Hoffmann-La Roche

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

Efficacy and safety of giredestrant (GIRE) in patients (pts) with estrogen receptor–positive, HER2-negative early breast cancer (ER+, HER2– eBC) in the phase III lidERA BC clinical trial: Results by menopausal status. (ASCO 2026) - P3 | " Pts with ER+, HER2– eBC who had BC surgery and (neo)adjuvant chemotherapy (if indicated) were randomized 1:1 to once-daily 30 mg GIRE or SOC ET (anastrozole/letrozole/exemestane [aromatase inhibitors; AIs] or tamoxifen [TAM]) for 5 years (y) of treatment (tx). Adjuvant GIRE improved IDFS and DRFI vs SOC ET; benefit was consistent irrespective of menopausal status. PRE-M pts experienced a 42% reduction in the risk of developing metastatic disease and POST-M pts a 24% reduction. Safety was comparable between menopausal groups and there were few discontinuations, regardless of menopausal status, although PRE-M and POST-M pts receiving GIRE had fewer tx discontinuations than those receiving an AI or TAM in the PRE-M and POST-M settings."

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 • Musculoskeletal Diseases • Musculoskeletal Pain • 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

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

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

lidERA Breast Cancer (BC): Phase III adjuvant study of giredestrant vs. physician’s choice of endocrine therapy (PCET) in patients (pts) with estrogen receptor-positive, HER2-negative early BC (ER+, HER2– eBC). (ASCO 2023) - P3 | "It is more potent in vitro and achieves higher ER occupancy in vivo than fulvestrant...Pts are randomized 1:1 to oral 30 mg daily giredestrant or PCET (tamoxifen, anastrozole, letrozole, or exemestane; per prescribing information)...2950/4100 pts have been recruited globally. Clinical trial information: NCT04961996."

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