Preoperative Window Opportunity Study With Giredestrant or Tamoxifen in Premenopausal Women With ER+/HER2[-] & Ki67≥10%

NCT05659563 | Completed Phase 2 Results DMC

• 3 other identifiers: MEDOPP4592022-002166-332023-503565-36-00
• Study Type: interventional
• Target: 92
• Locations: 2 countries
• Sites: 18

Brief Summary

This study is a window of opportunity clinical trial to evaluate the efficacy of giredestrant (GDC-9545) or tamoxifen in estrogen receptor-positive (ER\[+\])/human epidermal growth factor receptor 2-negative (HER2\[-\]) primary invasive adenocarcinoma of the breast with Ki67 level ≥ 10%. A total of 92 patients will be enrolled in this trial and randomized 1:1 in the arm A with giredestrant (GDC-9545) and the arm B with tamoxifen, with a total duration of treatment of 15 days. This study will analyze the efficacy of giredestrant (GDC-9545) as determined by Ki67 expression between baseline tumor biopsy samples and post-treatment biopsy samples.

Conditions

Breast Cancer; Breast Cancer, Early-Onset

Outcome Measures

Primary Outcomes (1)

• Change in Proliferative Index (Ki67 Expression)

  To assess changes in tumor cell proliferation as measured by Ki67 expression between baseline and D15 (+1 day) post-treatment tumor biopsy samples by central assessment in patients with centrally confirmed Ki67 ≥10% (Arm A: giredestrant vs Arm B: tamoxifen)

  Baseline up to 15 days

Secondary Outcomes (3)

• Complete Cell Cycle Arrest (CCCA)

  Baseline up to 15 days

• Changes in Molecular Profiles of Tumor Tissue Samples

  Baseline up to 15 days

• Changes in Expression Levels of Estrogen Receptor and Progesterone Receptor in Tumor Tissue Samples

  Baseline up to 15 days

Other Outcomes (2)

• Changes in Molecular Profiles of Plasma Biomarkers Related to Endocrine Function

  Baseline up to 15 days

• Incidence and Severity of Adverse Events

  Baseline up to 15 days

Study Arms (2)

Arm A

EXPERIMENTAL

Giredestrant (GDC-9545): 30mg, orally (PO), daily (QD) during 15 days

Drug: Giredestrant

Arm B

ACTIVE COMPARATOR

Tamoxifen: 20mg, orally (PO), daily (QD) during 15 days

Drug: Tamoxifen

Interventions

Giredestrant DRUG

Giredestrant is a highly potent, non-steroidal, oral selective ER antagonist and degrader (SERD)

Also known as: GDC-9545

Arm A

Tamoxifen DRUG

Tamoxifen is a selective estrogen receptor (ER) modulator

Also known as: Nolvadex® or Soltamox®

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form (ICF) prior to beginning specific protocol procedures.
• Aged ≥ 18 years at time of signing ICF.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Women in a well-determined premenopausal status as indicated in the protocol Section 4.1.
• Histologically confirmed invasive breast carcinoma, with all the following characteristics:
• Documented ER-positive tumor in accordance with American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines (Allison et al., 2020), assessed locally and defined as ≥ 1% of tumor cells stained positive.
• Documented HER2-negative tumor in accordance with 2018 ASCO/CAP guidelines (Wolff et al., 2018), assessed locally at baseline.
• Note: Diagnostic biopsy taken no more than 8 weeks prior to initiation of study treatment can be used as baseline.
• Ki67 score ≥10% analyzed locally and centrally confirmed (Nielsen et al., 2021).
• Tumor size must be ≥1.0 cm in longest diameter by ultrasound as per Response Evaluation Criteria in solid Tumors (RECIST) criteria.
• Note: Patients with multifocal or multicentric breast cancer with a at least one tumor lesion ≥1.0 cm in the longest diameter by ultrasound (reference lesion) are also eligible if the two largest lesions have been histologically confirmed in the clinical evaluation and meet pathologic criteria for ER positivity and HER2 negativity.
• Willingness to provide a primary tumor tissue and blood sample obtained at baseline as well as a post-treatment tumor tissue and blood samples (breast biopsy or from breast surgery).
• Patient has adequate bone marrow, liver, and renal function:
• Hematological: absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1500/mL), platelet count ≥ 100.0 x109/L, and hemoglobin ≥ 9 g/dL (≥ 90g/L).
• Note: The blood counts are to meet the specified criteria without transfusion or growth factor support, unless it is clear that the bone marrow function is adequate and that any aberration has a clear and correctable cause, and the correction undertaken.

You may not qualify if:

• Patients will be excluded from the study if they meet ANY of the following criteria:
• Progesterone receptor (PgR)\[+\] and ER\[-\] patients.
• cT4 and/or cN2/3 and/or bilateral BC.
• Patients who have history of any prior (ipsilateral and/or contralateral) invasive BC or Ductal carcinoma in situ (DCIS). Participants with a history of contralateral DCIS treated by only local regional therapy at any time may be eligible.
• Evidence of metastatic disease.
• Previous systemic or local treatment for the primary BC currently under investigation.
• History of any prior treatment with chemotherapy drugs, aromatase inhibitors (AIs), tamoxifen, selective estrogen receptor down regulator, or cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i).
• Any invasive malignancy diagnosed within the previous 5 years prior to screening in this study (other than basal cell carcinoma, cervical carcinoma in situ or contralateral DCIS).
• Known issues with swallowing oral medication, or inability or unwillingness to swallow oral medication.
• Participants who have a known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including hepatitis (e.g., hepatitis B virus \[HBV\] or hepatitis C virus \[HCV\]), current alcohol abuse, cirrhosis, or positive test for viral hepatitis, as defined below:
• Active infection is defined as requiring treatment with antiviral therapy or presence of positive test results for hepatitis B (hepatitis B surface antigen and/or total hepatitis B core antibody \[HBcAb\]) or HCV antibody. Unless required by local regulations, participants are not required to have HBV, or HCV assessments at screening if these assessments have not been previously performed.
• Participants who test positive for HBcAb are eligible only if test results are also positive for hepatitis B surface antibody and polymerase chain reaction is negative for HBV DNA Participants who are positive for HCV serology are eligible only if testing for HCV RNA is negative.
• Active cardiac disease or history of cardiac dysfunction including any of the following:
• History or presence of symptomatic bradycardia or sick sinus syndrome.
• Resting heart rate \< 50 bpm at screening.

Sponsors & Collaborators

• MedSIR: lead

Study Sites (18)

Hopital Europeen Georges Pompidou

Paris, Paris, France

Location

Hôpital Tenon AP-HP

Paris, France

Location

Hospital General Universitario Dr. Balmis

Alicante, Alicante, 03010, Spain

Location

Institut Català d' Oncologia Badalona

Badalona, Barcelona, Spain

Location

Hospital Clínic i Provincial de Barcelona

Barcelona, Barcelona, Spain

Location

Hospital Universitari Dexeus

Barcelona, Barcelona, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, Cordoba, Spain

Location

Hospital Universitario Clínico San Cecilio de Granada

Granada, Granada, 18016, Spain

Location

Hospital Beata Maria Ana

Madrid, Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Madrid, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Madrid, Spain

Location

Hospital Clínico Universitario Virgen de la Arrixaca

Murcia, Murcia, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Sevilla, 41013, Spain

Location

Hospital Universitari Sant Joan de Reus

Reus, Tarragona, Spain

Location

Hospital Arnau de Vilanova de Valencia

Valencia, Valencia, 46015, Spain

Location

Hospital Universitario de León

León, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, Spain

Location

Instituto Valenciano de Oncología

Valencia, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

giredestrant; Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Chief Scientific Officer
• Organization: Medica Scientia Innovation Research (MEDSIR)

contact.trials@medsir.org

+34 932 214 135

Study Officials

• Antonio Llombart, MD

  Arnau de Vilanova Hospital, Valencia (Spain)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter, international, open-label, two-arms, one stage, phase II, window of opportunity, clinical trial

Study Record Dates

• First Submitted: December 5, 2022
• First Posted: December 21, 2022
• Study Start: July 20, 2023
• Primary Completion: January 30, 2025
• Study Completion: January 30, 2025
• Last Updated: March 19, 2026
• Results First Posted: March 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (16); FR (2)