Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Estrogens

Giredestrant will be administered orally once daily (QD) starting on Day 1 up to and including the day of surgery (if allowed per local process) on Day 15 (+/-2 days).

Giredestrant

Breast cancer surgery will take place on Day 15 (+/-2 days).

Surgery

Clinical Trials

This study will evaluate the pharmacodynamics, pharmacokinetics, safety, and biologic activity of giredestrant in participants with Stage I-III operable estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, untreated breast cancer.

A Study of Giredestrant (GDC-9545) in Postmenopausal Women With Stage I-III Operable, Estrogen Receptor-Positive Breast Cancer

A Phase I, Multicenter, Open-Label Preoperative, Short-Term Window Study of GDC-9545 in Postmenopausal Women With Stage I-III Operable, Estrogen Receptor-Positive Breast Cancer

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The biological response to the study treatment was assessed by measuring changes in cell proliferation (Ki67 expression) using formalin-fixed paraffin-embedded histopathology sections of the tumor biopsy specimens taken at baseline and at day of surgery. Baseline was defined as a sample taken prior to initiation of study drug. The results show the proportion of nuclei staining Ki67-positive (Ki67+) in the tumor biopsy sample taken post-treatment (at surgery) relative to that in the pre-treatment sample (at baseline).

The biological response to the study treatment was assessed by measuring changes in cell proliferation (Ki67 expression) using formalin-fixed paraffin-embedded histopathology sections of the tumor biopsy specimens taken at baseline and at day of surgery. Baseline was defined as a sample taken prior to initiation of study drug. The results show the percentage of nuclei staining Ki67-positive (Ki67+) in the pre- and post-treatment tumor biopsy samples (taken at baseline and surgery, respectively) and the absolute difference in the percentage of Ki67+ nuclei between the two samples (calculated as surgery minus baseline).

All adverse events (AEs) were recorded and the investigator independently assessed the seriousness and severity of each AE. AE severity was graded on a scale from 1 to 5 using the NCI-CTCAE v5.0; any events not specifically listed in the scale were defined as: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening; and Grade 5 is death related to an AE. Investigators used their knowledge of the patient, the circumstances surrounding the event, and an evaluation of any potential alternative causes to determine whether an AE was considered to be related to the study drug.

Vital signs, which included diastolic and systolic blood pressure, pulse rate, and body temperature, were measured while the participant was sitting and according to institutional practices. Any of the vital signs that were outside of the normal reference range (in the specified direction - low or high) were considered abnormalities. Not every abnormality qualified as an adverse event (AE). A vital sign result had to be reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment.

Pulse rate was measured while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit. Baseline was defined as the participant's last value prior to initiation of study drug.

Systolic blood pressure was measured while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit. Baseline was defined as the participant's last value prior to initiation of study drug.

Diastolic blood pressure was measured while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit. Baseline was defined as the participant's last value prior to initiation of study drug.

Body temperature was measured according to institutional practice. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit. Baseline was defined as the participant's last value prior to initiation of study drug.

Laboratory parameters for hematology will be measured and compared with a standard reference range. Any of the laboratory test results that were outside of a parameter's normal reference range (in the specified direction - low or high) were considered abnormalities. Not every laboratory abnormality qualified as an adverse event (AE). A laboratory test result was reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment.

Laboratory parameters for blood chemistry and coagulation were measured and compared with a standard reference range. Any of the laboratory test results that were outside of a parameter's normal reference range (in the specified direction - low or high) were considered abnormalities. Not every laboratory abnormality qualified as an adverse event (AE). A laboratory test result was reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. SGPT/ALT = alanine aminotransferase; SGOT/AST = aspartate aminotransferase

Electrocardiogram (ECG) recordings were performed after the participant had been resting in a supine position for at least 10 minutes. ECG parameters included heart rate, PR and QRS durations, and QT and QTcF intervals. Per the protocol, ECG readings post-treatment were limited to those for whom it was clinically indicated. Any of the ECG parameters that were outside of the normal reference range (in the specified direction - low or high) were considered abnormalities. Not every abnormality qualified as an adverse event (AE). An ECG test result was reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment.

Plasma samples were obtained on the day of surgery (Day 15), or prior to biopsy on Day 14.

Genentech, Inc.

Giredestrant 10 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.

Giredestrant 10 mg

Giredestrant 30 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.

Giredestrant 30 mg

Giredestrant 100 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.

Giredestrant 100 mg

This analysis set includes a subset of the safety-evaluable participants who had ECG readings post-treatment because, per the protocol, ECGs were limited to those for whom it was clinically indicated. Participants in the three cohorts received giredestrant (10 mg, 30 mg, or 100 mg) that was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.

All Participants, Safety: Giredestrant (10, 30, or 100 mg)

Total

Age was missing for one participant in the giredestrant 100 mg arm because of early withdrawal from the study.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

In order to enroll in the study, a participant was required to have an ECOG performance status ≤1; statuses of 0 and 1 are defined as follows: 0 = Fully active, able to carry on all pre-disease performance without restrictions; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework or office work).

ECOG performance status was missing for one participant in the giredestrant 100 mg arm because of early withdrawal from the study.

Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline

The TNM description is used to assign an overall stage for breast cancer. There are 5 stages, usually written as Roman numerals: Stage 0 (in-situ breast cancer), followed by Stages I to IV (metastatic breast cancer). Generally, the higher the stage number, the more the cancer has spread. Stage I - the tumor is usually small and hasn't grown outside of the organ it started in. Stages II and III - the tumor is larger or has grown outside of the organ it started in to nearby tissue.

Initial Staging of Breast Cancer (Breast Cancer History)

The tumor grade is a description of how the cancer cells look compared to normal cells. A pathologist looks at a tissue sample from the tumor under a microscope and assigns a grade ranging from Grade 1 (low) to Grade 3 (high). The higher the grade, the more abnormal the cells look. Higher grade cancer cells tend to grow more quickly and are more likely to spread than low-grade cancer cells.

Tumor Grade (Breast Cancer History)

Nodal Status (Breast Cancer History)

This is the Intent-to-Treat (ITT) Population, which includes all participants enrolled in the study regardless of whether they received any study drug.

Medical Communications

This analysis set includes all efficacy-evaluable participants. Participants in the three cohorts received giredestrant (10 mg, 30 mg, or 100 mg) that was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.

All Participants, Efficacy: Giredestrant (10, 30, or 100 mg)

Efficacy Evaluable Population: all participants who 1) had non-missing baseline and post-baseline Ki67 results available, 2) did not discontinue early from the study, 3) had taken at least 12 doses, and 4) had no more than one modified dose. A total of 10 participants (2 in the 10mg cohort, 5 in the 30mg cohort, and 3 in the 100mg cohort) were excluded from efficacy evaluation for not meeting the criteria.

Change From Baseline in Tumor Cell Proliferation, as Measured by the Proportion of Nuclei Staining Ki67-Positive at Surgery Relative to Baseline in Pre- and Post-Treatment Tumor Biopsy Samples

Baseline (BL) - Value at Visit

Surgery - Value at Visit

Change from BL at Surgery (Surgery minus BL)

Change From Baseline in Tumor Cell Proliferation, as Measured by the Difference in the Percentage of Nuclei Staining Ki67-Positive at Surgery Compared With Baseline in Pre- and Post-Treatment Tumor Biopsy Samples

Any Adverse Event (AE)

AE with Fatal Outcome

Serious AE

Related Serious AE

AE Leading to Withdrawal from Study Drug

AE Leading to Interruption of Study Drug

Related AE

Grade 3-4 AE

Related Grade 3-4 AE

This analysis set includes all safety-evaluable participants. Participants in the three cohorts received giredestrant (10 mg, 30 mg, or 100 mg) that was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.

Safety Evaluable Population: all participants who received at least one dose of giredestrant. One participant from the ITT population did not receive the study drug because of early withdrawal from the study.

Number of Participants With at Least One Adverse Event and by Severity, Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0)

Diastolic Blood Pressure - Low

Diastolic Blood Pressure - High

Systolic Blood Pressure - High

Pulse Rate - Low

Pulse Rate - High

Body Temperature - Low

Percentage of Participants With Abnormal Vital Signs During Treatment

Change from BL at Day 8

Change from BL at Surgery

Change from BL at Post-Surgery

Change from BL at Post-BL Minimum

Change from BL at Post-BL Maximum

Safety Evaluable Population: all participants who received at least one dose of giredestrant. One participant from the ITT population did not receive the study drug because of early withdrawal from the study. The number analyzed indicates all participants who had a non-missing assessment at a given timepoint.

Change From Baseline in Pulse Rate

Change From Baseline in Systolic Blood Pressure

Change From Baseline in Diastolic Blood Pressure

Change From Baseline in Body Temperature

Hematocrit - Low

Hematocrit - High

Hemoglobin - Low

Hemoglobin - High

Lymphocytes, Absolute Count (Abs) - Low

Lymphocytes, Abs - High

Neutrophils, Total, Abs - Low

Erythrocytes - Low

Total Leukocyte Count - Low

Safety Evaluable Population: the number of participants analyzed includes all participants who received at least one dose of giredestrant. The number analyzed for a given laboratory parameter represents the number of participants without an abnormality (in the specified direction) at baseline for that parameter.

Percentage of Participants With Laboratory Abnormalities in Hematology Tests During Treatment, Among Participants Without the Abnormality at Baseline

Albumin - Low

Albumin - High

Alkaline Phosphatase - High

SGPT/ALT - High

SGOT/AST - High

Bicarbonate HCO3 - Low

Bicarbonate HCO3 - High

Blood Urea Nitrogen - High

Calcium - High

Carbon Dioxide - High

Chloride - Low

Chloride - High

Creatinine - High

Direct Bilirubin - Low

Direct Bilirubin - High

Glucose, Fasting - High

Glucose, Fasting Unknown - High

Magnesium - High

Phosphorus - Low

Phosphorus - High

Potassium - High

Sodium - Low

Bilirubin - High

Protein, Total - Low

Protein, Total - High

Prothrombin Time - High

International Normalized Ratio - High

Activated Partial Thromboplastin Time - Low

Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline

PR Duration - Low

PR Duration - High

This analysis set includes a subset of the safety-evaluable participants who had electrocardiogram (ECG) readings post-treatment because, per the protocol, ECGs were limited to those for whom it was clinically indicated. Participants in the three cohorts received giredestrant (10 mg, 30 mg, or 100 mg) that was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.

All Participants, Safety (ECG): Giredestrant (10, 30, or 100 mg)

The analysis included a small number of participants who had ECG readings post-treatment because, per the protocol, ECGs were limited to those for whom it was clinically indicated.

Percentage of Participants With Abnormal Electrocardiogram Parameters During Treatment

The Pharmacokinetics Analysis Population consisted of all participants who received at least one dose of giredestrant and had a measurable concentration at the specific timepoint collected.

Spots Global Cancer Trial Database for A Study of Giredestrant (GDC-9545) in Postmenopausal Women With Stage I-III Operable, Estrogen Receptor-Positive Breast Cancer

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Study Description

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