giredestrant (RG6171) / Roche - LARVOL DELTA

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) - "Abstract is embargoed at this time."

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

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

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

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

MODULE 5: Current and Future Role of Oral Selective Estrogen Receptor Degraders (SERDs) for Progressive HR-Positive mBC (SABCS 2025) - "Sponsored by Genentech, a member of the Roche Group, Eli Lilly and Stemline Therapeutics Inc. Structural and mechanistic similarities and differences between fulvestrant and approved and investigational oral SERDs; implications for antitumor activity, tolerability and ease of use Published efficacy and safety results from the Phase III EMERALD trial evaluating elacestrant versus standard endocrine monotherapy for pretreated HR-positive, HER2-negative mBC; outcomes for patients with and without ESR1 mutations FDA approval of elacestrant for previously treated HR-positive, HER2-negative, ESR1-mutated mBC; optimal incorporation into management algorithms Key findings from the Phase III EMBER-3 study of imlunestrant alone or in combination with abemaciclib for patients with HR-positive, HER2-negative mBC pretreated with endocrine therapy with or without a CDK4/6 inhibitor Recent FDA approval of imlunestrant monotherapy for ER-positive, HER2-negative, ESR1-mutated advanced or..."

Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • ER • HER-2

Invitation to Roche’s Virtual Oncology/SABCS Investor Event (Roche Press Release) - "We are pleased to invite investors and analysts to participate in our virtual event on Thursday, 11 December 2025, to highlight new results from Roche’s breast cancer pipeline, including data from the Phase III lidERA breast cancer study evaluating giredestrant as an adjuvant endocrine treatment for people with ER+/HER2- BC that will be presented at the 48th San Antonio Breast Cancer Symposium (SABCS) from 9-12 December 2025."

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

Genentech’s Giredestrant Becomes the First Oral SERD to Show Superior Invasive Disease-Free Survival in Early Breast Cancer (Genentech Press Release) - "The study met its primary endpoint at a pre-planned interim analysis, showing a statistically significant and clinically meaningful improvement in invasive disease-free survival with giredestrant versus standard-of-care endocrine therapy...Overall survival data were immature at the time of interim analysis, but a clear positive trend was observed. Giredestrant was well tolerated and adverse events were consistent with its known safety profile, with no unexpected safety findings observed."

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

Interim analysis of giredestrant (GIRE) + inavolisib (INAVO) in MORPHEUS breast cancer (BC): A phase Ib/II study of GIRE treatment (rx) combinations in patients (pts) with estrogen receptor-positive (ER+), HER2-negative, locally advanced/metastatic BC (LA/mBC) (ESMO 2025) - P1/2 | "Results As of 9 January 2025, 40 pts with PIK3CA m tumours were enrolled in the GIRE + INAVO arm; 65% (26/40) had one prior line of therapy for LA/mBC; 35% (14/40) had two; 45% (18/40) had prior fulvestrant...With this expanded cohort (n = 40), we have confirmed preliminary results from SABCS 2023 (n = 15), comparing favourably with historical data including alpelisib, capivasertib, elacestrant, and imlunestrant in this post—CDK4/6i-treated population. Safety of GIRE + INAVO was consistent with known profiles, with good tolerability. Table: 508P GIRE + INAVO (N = 40) Confirmed ORR, n (%) Complete response Partial response 16 (40) 3 (8) 13 (33) ORR ( ESR1 mutation), n/n (%) ORR ( ESR1 no mutation detected), n/n (%) 10/13 (77) 6/25 (24) Clinical benefit rate, n (%) 28 (70) Median PFS, mo (95% confidence interval) 9.5 (7.3, 14.0) All-grade TRAEs, n (%) 39 (98) Grade 3 AEs, n (%)* 15 (38) AE leading to any rx discontinuation, n (%) 4 (10) Most common all-grade TRAEs..."

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 • PIK3CA

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 | Recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Jul 2026 ➔ Feb 2027

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

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

A Study to Evaluate the Efficacy and Safety of Giredestrant in Combination With Phesgo (Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf) Versus Phesgo in Participants With Locally Advanced or Metastatic Breast Cancer (heredERA Breast Cancer) (clinicaltrials.gov) - P3 | N=922 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

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

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 | Not yet recruiting | Sponsor: Genentech, Inc.

Monotherapy • New P1 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Giredestrant: Data from P3 persevERA trial (NCT04546009) in combination with palbociclib for 1L ER+/ HER2- metastatic breast cancer in 2026 (Roche) - Q3 2025 Results

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

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: " Giredestrant + everolimus with consistent benefit, including INV-PFS, ORR and DoR, across key subgroups irrespective of ESR1m status”; Metastatic breast cancer (Roche) - Q3 2025 Results

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

Vepdegestrant, a PROteolysis Targeting Chimera (PROTAC) estrogen receptor (ER) degrader, induces greater ER degradation and antitumor activity relative to selective ER degraders (SERDs) in preclinical ER+ breast cancer models (AACR-NCI-EORTC 2025) - "Here, we report preclinical ER degradation and antitumor activity of vepdegestrant compared with FDA-approved (fulvestrant and elacestrant) and investigational oral SERDs (giredestrant, camizestrant, amcenestrant, and imlunestrant). Our results indicate that vepdegestrant induces greater maximal ER degradation than investigational oral SERDs, elacestrant, or fulvestrant in WT ER+ breast cancer cell lines. Vepdegestrant also demonstrated greater TGI and ER degradation in vivo compared with fulvestrant in a WT ER+ breast cancer CDX model."

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

Giredestrant: Regulatory submissions in US/EU for post CDKi ER+/HER2- metastatic breast cancer (in combination with everolimus) in 2025 (Roche) - Q3 2025 Results: Regulatory submissions in US/EU for 1L ET sensitive ER+/HER2- metastatic breast cancer (in combination with palbociclib) in 2026; Regulatory submissions in US/EU for ER+ adjuvant breast cancer in 2027; Regulatory submissions in US/EU for 1L ER+/HER2+ breast cancer (in combination with Phesgo) in 2027; Regulatory submissions in US/EU for 1L ET resistant ER+/HER2- breast cancer in 2027

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

Giredestrant: Regulatory submission in Japan for 1L-3L breast cancer in 2026 (Chugai) - Q3 FY2025 Results: Regulatory submission in Japan for 1L breast cancer in 2026; Regulatory submission in Japan for adjuvant breast cancer in 2027

Japan filing • Breast Cancer • Oncology

Roche’s phase III evERA data showed giredestrant significantly improved progression-free survival in people with ER-positive advanced breast cancer (Roche Press Release) - "In the ITT population, the median PFS was 8.77 months compared with 5.49 months in the giredestrant and comparator arms, respectively (stratified hazard ratio [HR]=0.56; 95% CI: 0.44-0.71, p-value= <0.0001). In the ESR1-mutated population, the median PFS was 9.99 months compared with 5.45 months in the giredestrant and comparator arms, respectively (HR=0.38; 95% CI: 0.27-0.54, p-value= <0.0001). The PFS benefit was consistent across pre-specified subgroups in both populations. Overall survival (OS) data were immature at the time of analysis, but a clear positive trend has been observed in the ITT (HR=0.69, 95% CI: 0.47-1.00, p-value=0.0473) and ESR1-mutated populations (HR=0.62, 95% CI: 0.38-1.02, p-value=0.0566)."

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

Giredestrant significantly reduced tumor proliferation compared with tamoxifen in premenopausal women with estrogen receptor–positive, HER2-negative (ER+/HER2−) early breast cancer (EBC), according to results from the phase 2 EMPRESS trial presented at the European Society for Medical Oncology Congress 2025 (DocWire) - "The investigators reported that giredestrant produced a greater reduction in tumor proliferation, with mean Ki67 decreasing by -14.5 (95% confidence interval [CI], -17.5 to -13.0) compared with -10.0 (95% CI, -12.3 to -8.5) with tamoxifen (P=0.002), meeting the primary end point. Rates of complete cell-cycle arrest (Ki67 ≤ 2.7%) at day 15 were numerically higher with giredestrant (17.5% vs 4.5%; P=0.074)."

P2 data • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

EndomERA: A Study of Giredestrant in Participants With Grade 1 Endometrial Cancer (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Dec 2025 ➔ Jun 2026 | Trial primary completion date: Dec 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Endometrial Cancer • Oncology • Solid Tumor

acelERA BC: A Study Evaluating the Efficacy and Safety of Giredestrant Compared With Physician's Choice of Endocrine Monotherapy in Participants With Previously Treated Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer (acelERA Breast Cancer) (clinicaltrials.gov) - P2 | N=303 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jun 2025 ➔ Aug 2027

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

Breast, lung, and bladder cancer phase 3 trials led by Dana-Farber presented at ESMO Congress 2025 (Eurekalert) - "Dana-Farber investigators will also present clinical trial results that report improved quality of life for metastatic breast cancer patients; new approaches, based on early investigations, to using blood tests to guide the treatment of kidney cancer; and new ways to analyze real-world data with artificial intelligence."

Clinical data • Real-world • Bladder Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Non Small Cell Lung Cancer • Triple Negative Breast Cancer

Giredestrant: Primary results from the phase III evERA Breast Cancer study… (Roche Press Release) - "The study met both co-primary endpoints, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival in both the intention-to-treat and ESR1-mutated populations. Data will be presented as a late-breaking oral abstract."

Late-breaking abstract • P3 data • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

AFT-50 EndoMAP: A Study of Targeted Agents for Patients With Recurrent or Persistent Endometrial Cancer (clinicaltrials.gov) - P1/2 | N=148 | Recruiting | Sponsor: Alliance Foundation Trials, LLC. | Trial completion date: Oct 2026 ➔ Oct 2027 | Trial primary completion date: Oct 2025 ➔ Oct 2026

IO biomarker • MSI-H • MSi-H Companion diagnostic • PARP Companion diagnostic • PD(L)-1 companion diagnostic • Trial completion date • Trial primary completion date • Endometrial Cancer • Oncology • Solid Tumor