giredestrant (RG6171) / Roche - LARVOL DELTA

GDC-4198, a next-generation CDK4/2 inhibitor, induces durable cell cycle arrest and shows combination benefit with giredestrant (AACR 2026) - "Additional studies in patient-derived cell lines obtained in the setting of metastatic HR+ breast cancer following progression on letrozole/ribociclib, as well as in cell lines with acquired in vitro resistance to palbociclib, confirmed the enhanced anti-proliferation activity of GDC-4198 compared to CDK4/6i.When combined with giredestrant, GDC-4198 showed strong combination benefits across a range of HR+ BC cell lines. Pharmacokinetic and pharmacodynamic analyses indicated pRb modulation in tumor samples correlated with drug exposure.Taken together, these preclinical findings demonstrate that GDC-4198 induces more durable cell cycle arrest than first generation CDK4/6i and CDK4-targeting agents by overcoming CDK2-driven adaptive and intrinsic resistance to CDK4 inhibition. These results suggest that GDC-4198 is a promising next generation CDK4/2 inhibitor with the potential to prolong clinical benefit by delaying adaptation in earlier disease settings, as well as to..."

Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CCNE1 • ER

A liquid biopsy assay of estrogen receptor activity predicts response to giredestrant in ER+/HER2− advanced breast cancer (AACR 2026) - "PERDI quantifies plasma-based ER activity and predicts giredestrant benefit, particularly when integrated with ESR1 genotype or ctDNA tumor fraction. PERDI also showed early evidence of PD change directly from plasma, mitigating the need for serial tumor biopsies. cfDNA-based gene expression modeling enables noninvasive assessment of ER dependence and response-associated transcriptional programs, offering a scalable framework for monitoring endocrine response and adaptation in ER+/HER2− aBC."

Biopsy • Liquid biopsy • Metastases • 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

TGFβ Induction: An essential tumor suppressive arm of next generation SERDs in ER+ breast cancer models in vitro (AACR 2026) - "This finding shows that CDK4/6/2 blockade can bypass, in-part, the requirement for the p21 cell cycle brake.Collectively, our results reveal that giredestrant's in vitro efficacy relies on an autocrine TGFβ loop to mediate the necessary G1 arrest. The inhibition of TGFβ creates a resistance mechanism by neutralizing this essential tumor-suppressive signaling component."

Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CDKN1A • ER • SMAD4 • TGFB1 • TGFBR2

Ligand-activated AR promotes the survival of endocrine therapy-responsive ER+ breast cancer (AACR 2026) - P3 | "Giredestrant, a next-generation oral selective ERα degrader (SERD), is a potent and full antagonist that recently demonstrated statistically significant and clinically meaningful improvement in progression free survival (PFS) in the phase III evERA Breast Cancer trial (NCT05306340)...Transcriptomic data suggest that this is mediated by the suppression of proliferation-associated programs, potentially through PI3K/mTOR pathway inhibition. By leveraging the novel mouse intraductal model, we identified dual ER and AR blockade, as well as ER-PI3K/mTOR pathway co-targeting, as promising therapeutic strategies to improve outcomes for premenopausal women with ER+ breast cancer, particularly those not receiving GnRH agonists."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor

ENABLING HEALTH TECHNOLOGY ASSESSMENT (HTA) TA READINESS THROUGH REAL-TIME AI-ASSISTED LIVING SYSTEMATIC LITERATURE REVIEWS (REAL-SLR): A BREAST CANCER (BCA) CASE STUDY (ISPOR 2026) - "REAL-SLR enables a shift from episodic SLRs to a continuously maintained HTA evidence foundation. By supporting real-time incorporation of emerging data and rapid alignment to HTA requirements, REAL-SLR improves preparedness, reduces rework, and enhances transparency for oncology HTA decision making."

Case study • Clinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • 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

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

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

ctDNA and tumor-based biomarkers of giredestrant response in acelERA breast cancer. (PubMed, Nat Commun) - P2 | "Furthermore, early ctDNA clearance identifies responding patients, and the combination of low ER activity and high ctDNA burden predicts rapid clinical progression. These findings provide a framework for personalizing future breast cancer therapies by integrating liquid biopsies with tissue-based signatures."

Biomarker • Circulating tumor DNA • Journal • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER

Giredestrant vs standard-of-care endocrine therapy as adjuvant treatment for patients with estrogen receptorpositive, HER2-negative early breast cancer: Results from the global Phase III lidERA Breast Cancer trial (MBCC 2026) - No abstract available

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

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) - No abstract available

Clinical • Metastases • 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

The United States Food and Drug Administration (FDA) recently accepted the New Drug Application based on the evERA data. (Roche Press Release) - "In the coming weeks, Roche will submit the giredestrant phase III lidERA data in early-stage breast cancer to the FDA."

FDA event • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

GO39932: A Study of GDC-9545 Alone or in Combination With Palbociclib and/or Luteinizing Hormone-Releasing Hormone (LHRH) Agonist in Locally Advanced or Metastatic Estrogen Receptor-Positive Breast Cancer (clinicaltrials.gov) - P1 | N=181 | Active, not recruiting | Sponsor: Genentech, Inc. | Phase classification: P1a/1b ➔ P1

Phase classification • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

A Study to Evaluate the Effect of GDC-4198 Alone and in Combination With Giredestrant Versus Abemaciclib and Giredestrant in Participants With Locally Advanced or Metastatic Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor-Negative (HER2-) Breast Cancer (clinicaltrials.gov) - P1/2 | N=285 | Recruiting | Sponsor: Genentech, Inc. | Trial completion date: Jul 2030 ➔ Aug 2028 | Trial primary completion date: Jul 2030 ➔ Aug 2028

Trial completion date • 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 • HER-2

The pionERA study of giredestrant in combination with physician’s choice of cyclin-dependent kinase (CDK)4/6 inhibitor in endocrine-resistant ER-positive, HER2-negative breast cancer is expected to readout in 2027. (Roche Press Release)

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

GO39932: A Study of GDC-9545 Alone or in Combination With Palbociclib and/or Luteinizing Hormone-Releasing Hormone (LHRH) Agonist in Locally Advanced or Metastatic Estrogen Receptor-Positive Breast Cancer (clinicaltrials.gov) - P1a/1b | N=181 | Active, not recruiting | Sponsor: Genentech, Inc. | Trial completion date: Sep 2022 ➔ Mar 2023 | Trial primary completion date: Sep 2022 ➔ Mar 2023

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

GO39932: A Study of GDC-9545 Alone or in Combination With Palbociclib and/or Luteinizing Hormone-Releasing Hormone (LHRH) Agonist in Locally Advanced or Metastatic Estrogen Receptor-Positive Breast Cancer (clinicaltrials.gov) - P1a/1b | N=130 | Recruiting | Sponsor: Genentech, Inc.

New P1 trial • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

GO39932: A Study of GDC-9545 Alone or in Combination With Palbociclib and/or Luteinizing Hormone-Releasing Hormone (LHRH) Agonist in Locally Advanced or Metastatic Estrogen Receptor-Positive Breast Cancer (clinicaltrials.gov) - P1a/1b | N=220 | Recruiting | Sponsor: Genentech, Inc. | N=150 ➔ 220 | Trial completion date: Jul 2021 ➔ Oct 2021 | Trial primary completion date: Jul 2021 ➔ Oct 2021

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

GO46021: To compare the Safety and activity of GDC-4198 Alone and in Combination with Giredestrant against Abemaciclib and Giredestrant in Participants with Breast Cancer (clinicaltrialsregister.eu) - P1/2 | N=73 | Recruiting | Sponsor: Genentech Inc.

New P1/2 trial • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

GO39932: A Study of GDC-9545 Alone or in Combination With Palbociclib and/or Luteinizing Hormone-Releasing Hormone (LHRH) Agonist in Locally Advanced or Metastatic Estrogen Receptor-Positive Breast Cancer (clinicaltrials.gov) - P1a/1b | N=181 | Active, not recruiting | Sponsor: Genentech, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Safety and preliminary efficacy of giredestrant (GIRE) + the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) + palbociclib (PALBO) in MORPHEUS Breast Cancer (BC): A Phase Ib/II trial in patients (pts) with oestrogen receptor-positive, HER2-positive (ER+, HER2+) metastatic (m)BC (ESMO-BC 2026) - No abstract available

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

[Ad hoc announcement pursuant to Art. 53 LR] Roche provides update on phase III persevERA study in ER-positive advanced breast cancer (Roche Press Release) - "persevERA Breast Cancer study did not meet the primary objective of a statistically significant improvement in progression-free survival, but a numerical improvement was observed; Giredestrant plus palbociclib was well tolerated and adverse events were consistent with the known safety profiles of each individual treatment...Roche will continue to advance the clinical development programme to identify the people with ER-positive breast cancer who can derive the greatest benefit from giredestrant."

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

GO39932: A Study of GDC-9545 Alone or in Combination With Palbociclib and/or Luteinizing Hormone-Releasing Hormone (LHRH) Agonist in Locally Advanced or Metastatic Estrogen Receptor-Positive Breast Cancer (clinicaltrials.gov) - P1a/1b | N=181 | Active, not recruiting | Sponsor: Genentech, Inc. | Trial completion date: Jul 2022 ➔ Sep 2022 | Trial primary completion date: Jul 2022 ➔ Sep 2022

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

GO39932: A Study of GDC-9545 Alone or in Combination With Palbociclib and/or Luteinizing Hormone-Releasing Hormone (LHRH) Agonist in Locally Advanced or Metastatic Estrogen Receptor-Positive Breast Cancer (clinicaltrials.gov) - P1a/1b | N=220 | Recruiting | Sponsor: Genentech, Inc. | Trial completion date: Oct 2021 ➔ Jul 2022 | Trial primary completion date: Oct 2021 ➔ Jul 2022

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