giredestrant (GDC-9545) / Roche - LARVOL DELTA

A Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With the Physician's Choice of Endocrine Therapy Plus Everolimus in Participants With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (evERA Breast Cancer) (clinicaltrials.gov) - P3 | N=373 | Active, not recruiting | Sponsor: Genentech, Inc. | Trial primary completion date: Oct 2026 ➔ Jul 2025

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

Development of efficient manufacturing processes for GDC-9545 (Giredestrant) and GDC-5573 (Belvarafenib) (ACS-Fall 2025) - "They also highlight the impact that high-throughput experimentation can have on facilitating expedient identification of metal-catalyzed reaction conditions. Finally, this presentation will describe some of the challenges associated with the development of chemical processes towards an HHC Category 3B API with particularly poor physical properties at multiple stages of the synthetic sequence, including the API itself."

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) - No abstract available

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

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) - 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

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 | Not yet 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

A Study Evaluating the Efficacy and Safety of Adjuvant Giredestrant Compared With Physician's Choice of Adjuvant Endocrine Monotherapy in Participants With Estrogen Receptor-Positive, HER2-Negative Early Breast Cancer (lidERA Breast Cancer) (clinicaltrials.gov) - P3 | N=4200 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Nov 2033 ➔ Jan 2035

Monotherapy • Trial completion date • 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

Novel regimens for persistent/recurrent rare epithelial ovarian carcinomas (EOCs) selected according to biomarker status: ENGOT-GYN2/GOG-3051/BOUQUET phase II study results (ESMO-GC 2025) - P2 | "We report results from combination regimens including inavolisib (inavo, a PI3Kα-selective inhibitor), giredestrant (gire, an oral selective oestrogen receptor degrader [SERD]), CDK4/6 inhibitors, letrozole, bevacizumab (bev), olaparib and atezolizumab (atezo)...Results In PIK3CA-mutated rare EOC, the cORR with inavo + palbociclib (palbo) was 25% (4 partial responses all in pts with clear-cell [CC] tumours) and median progression-free survival (PFS) was 8 mo. Gire + abemaciclib (abema) showed a 5% cORR but sustained disease control and a 58% 6-mo PFS rate in ER+ (mostly low-grade serous [LGS]) EOC. In non-matched pts, atezo + bev + metronomic cyclophosphamide (cyclo) showed a 32% cORR, including complete responses in 1 pt with LGS and 1 with mucinous carcinoma; the cORR was 0% with inavo + olaparib...Editorial acknowledgement J. Kelly (Medi-Kelsey Ltd). Legal entity responsible for the study F. Hoffmann-La Roche Ltd."

Biomarker • P2 data • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • ER • PIK3CA

Giredestrant (G) with atezolizumab (ATEZO), and/or abemaciclib (ABEMA) in patients (pts) with ER+/HER2– locally advanced/metastatic breast cancer (LA/mBC): Interim analysis (IA) from the phase I/II MORPHEUS Breast Cancer study. (ASCO 2025) - P1/2 | "Many pts had prior fulvestrant (60%, 43%, and 27%, respectively) and prior CDK4/6i duration ≥12 mo (73%, 77%, and 53%). The combinations of G + ATEZO, G + ATEZO + ABEMA, and G + ABEMA were tolerable, with no unexpected safety signals including no high-grade interstitial lung disease/pneumonitis and low rates of high-grade liver toxicity. Clinical activity was observed, with a trend towards improved ORR with G + ATEZO + ABEMA, particularly in tumors with ESR1 mutations."

Clinical • IO biomarker • Metastases • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Interstitial Lung Disease • Neutropenia • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • ER • HER-2

Carrick Therapeutics Announces New Clinical Data Supporting Biomarker-driven Patient Selection for Samuraciclib (CDK7i) in Combination with SERDs in Hormone Receptor Positive Advanced Breast Cancer (GlobeNewswire) - "Carrick Therapeutics Inc...today announced results from a new analysis of two Phase 2 clinical trials of samuraciclib...in patients with hormone receptor positive (HR+) advanced breast cancer who had received prior CDK4/6 inhibitor therapy. The MORPHEUS trial evaluated samuraciclib in combination with giredestrant and the Module 2A trial evaluated samuraciclib in combination with fulvestrant....The analysis indicated that study participants with no evidence of a deleterious mutation in the TP53 gene in circulating tumor DNA at baseline or separately, without liver metastases at baseline, experienced extended durations of progression-free survival....Results of the data analysis indicated improved progression-free survival both for patients with no TP53 mutation, compared to those with mutation, and also for patients without liver metastases, compared to those with liver metastases."

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

Patient selection biomarkers for CDK7 inhibitor samuraciclib (SAM; CT7001) combined with selective estrogen receptor degrader (SERD) in hormone receptor-positive advanced breast cancer (HR+ ABC) post-CDK4/6 inhibitor (CDK4/6i) (ESMO-BC 2025) - P1/2 | "SAM was administered to patients (pts) with HR+ ABC with fulvestrant (FUL), an intramuscular (IM) SERD, or giredestrant (GIR), a highly potent, non-steroidal, PO SERD, in 2 independent studies: CT7001_001 (NCT03363893) Module 2A and MORPHEUS (NCT04802759) [Coombes et al. These independent studies suggest that patients with no evidence of either TP53 mutation or of liver metastases may preferentially benefit from SAM + SERD. The observed outcomes in this small dataset appear greater than the anticipated prognostic impact of these factors [O'Leary et al. JNCI 2021; Robertson et al."

Biomarker • Clinical • Metastases • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • CDK7 • ER • TP53

Giredestrant: Data from P3 persevERA trial (NCT04546009) in combination with palbociclib for 1L ER+/ HER2- metastatic breast cancer in H2 2025 (Roche) - Q1 2025 Results: Data from P3 evERA trial (NCT05306340) in combination with everolimus for post CDKi ER+/HER2- metastatic breast cancer in H2 2025

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

Giredestrant: Regulatory submission in Japan for 1L-3L breast cancer in 2026 (Chugai) - Q1 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

Giredestrant: Regulatory submissions in US/EU for post CDKi ER+/HER2- metastatic breast cancer (in combination with everolimus) in 2025 (Roche) - Q1 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

ET-Based Combinations and Novel Agents in HR+/HER2- Advanced Breast Cancer (GBCC 2025) - "Tumors with alterations in the PIK3CA/AKT/PTEN pathway may be offered a pathway inhibitor such as capivasertib or alpelisib, and patients with high risk recurrence of HR+ disease with a PIK3CA mutation may benefit from early introduction of a first-line inavolisib triplet...The oral SERD elacestrant is approved as monotherapy in pretreated patients with tumors harboring an ESR1 mutation. Additional oral SERDs, including imlunestrant, camizestrant, and giredestrant, have demonstrated activity and are in registrational trials. An additional maneuver in the pretreated space includes continuation of a CDK4/6 inhibitor after prior CDK4/6 inhibitor, with activity seen from switching to abemaciclib or ribociclib from a prior agent, and novel CDK inhibitors are in trials as a next generation approach. The mTOR inhibitor everolimus remains an option for pretreated patients as well, particularly when actionable mutations are not present. The continued introduction of novel agents..."

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

A Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With the Physician's Choice of Endocrine Therapy Plus Everolimus in Participants With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (evERA Breast Cancer) (clinicaltrials.gov) - P3 | N=320 | Active, not recruiting | Sponsor: Genentech, Inc. | Trial completion date: Mar 2026 ➔ Oct 2026 | Trial primary completion date: Mar 2026 ➔ Oct 2026

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

MORPHEUS BC: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer (clinicaltrials.gov) - P1/2 | N=510 | Recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Apr 2026 ➔ Nov 2027

Trial primary completion date • 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 • CDK4 • ER

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 | N=510 ➔ 316

Enrollment change • 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 • CDK4 • ER

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 | Recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Mar 2027 ➔ Dec 2027

Trial primary completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive 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) - P1 | N=181 | Active, not recruiting | Sponsor: Genentech, Inc. | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • 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

Neo-AGILE: NEOadjuvant Abemaciclib and GIredestrant TriaL in Patients with ER-positive, HER2-negative Early Breast Cancer (clinicaltrials.gov) - P2 | N=51 | Recruiting | Sponsor: Fondazione Oncotech | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

A Study Evaluating the Efficacy and Safety of Adjuvant Giredestrant Compared With Physician's Choice of Adjuvant Endocrine Monotherapy in Participants With Estrogen Receptor-Positive, HER2-Negative Early Breast Cancer (lidERA Breast Cancer) (clinicaltrials.gov) - P3 | N=4200 | Recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Dec 2025 ➔ Mar 2026

Monotherapy • Trial primary completion date • 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

EMPRESS: Preoperative Window Opportunity Study With Giredestrant or Tamoxifen in Premenopausal Women With ER+/HER2[-] & Ki67≥10% (clinicaltrials.gov) - P2 | N=92 | Completed | Sponsor: MedSIR | Active, not recruiting ➔ Completed

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

New Oral Selective Estrogen Receptor Degraders Redefine Management of Estrogen Receptor-Positive Breast Cancer. (PubMed, Annu Rev Med) - "There are currently five oral SERDs in published and ongoing clinical trials-elacestrant, camizestrant, giredestrant, imlunestrant, and amcenestrant-with more in development. They offer a reasonably well-tolerated oral therapy option with low discontinuation rates in studies. This review summarizes the currently available literature on this new class of drugs."

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

MORPHEUS BC: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer (clinicaltrials.gov) - P1/2 | N=510 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Oct 2026 ➔ Nov 2027

Trial completion date • 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 • CDK4 • ER

Transformer-based modeling of Clonal Selection and Expression Dynamics reveals resistance mechanisms in breast cancer. (PubMed, NPJ Syst Biol Appl) - "When applied to cells treated with either giredestrant, a selective estrogen receptor (ER) antagonist and degrader, or palbociclib, a CDK4/6 inhibitor, pathways dynamically associated with resistance are revealed. Clustering based on partial least squares regression found that high baseline expression of both SNHG25 and SNCG genes was the primary marker of positive selection to co-treatment and thus potentially associated with innate resistance - an aspect that traditional differential analysis methods missed. In conclusion, TraCSED enables associating features with phenotypes in a time-dependent manner from scRNA-seq data."

Journal • Breast Cancer • Oncology • Solid Tumor • ER • SNHG5