Breast Cancer
Conditions
Keywords
SERD
Brief summary
The purpose for this study is to see if the study drug, LY3484356, is safe and to determine what effects it has on breast cancer in participants with Estrogen Receptor Positive (ER+), HER2 Negative (HER2-) early stage (stage I-III) breast cancer, when given prior to surgery. Participation in this study could last up to 2.5 months.
Interventions
DRUGLY3484356
Administered orally.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have histologically confirmed invasive ER+, HER2- breast carcinoma * Be willing and able to provide pre- and on-treatment tumor samples * Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale * Have adequate organ function * Be able to swallow capsules * Be a postmenopausal woman
Exclusion criteria
* Have bilateral invasive breast cancer * Have metastatic breast cancer * Plan to receive concurrent neoadjuvant therapy with any other non-protocol anti-cancer therapy * Have had prior therapy (of any kind) for an invasive or non-invasive breast cancer * Have had prior radiotherapy to the ipsilateral chest wall for any malignancy * Have had prior anti-estrogen therapy with raloxifene, tamoxifen, aromatase inhibitor, or other selective estrogen receptor modulator (SERM), either for osteoporosis or prevention of breast cancer * Have had prior hormone-replacement therapy within 4 weeks of the start of study treatment * Have had major surgery within 28 days prior to randomization to allow for post-operative healing of the surgical wound and site(s) * Have certain infections such as hepatitis or tuberculosis or HIV that are not well controlled * Have another serious medical condition * Have a history of any other cancer (except nonmelanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Estrogen Receptor (ER) Expression | Baseline, Day 15 | Tumor tissue collected by biopsy is used to determine ER expression. ER expression is measured by immunohistochemistry (IHC) and quantified by H-score. The H-score was calculated as the sum of multiplying the tumor cell ER staining intensity level 0 to 3 (0=none, 1=low, 2=moderate, 3=high) by the percentage (0 to 100) of cells at each intensity. Total ER H-score ranged from 0 to 300, where a higher score indicated stronger ER expression. Percent change in ER expression was defined as 100\*(ER expression on-treatment - ER expression pre-treatment)/(ER expression pre-treatment). Geometric mean percent change and 90 percent (%) confidence interval for percent change were obtained from a t-test of the log ratio i.e. log(ER expression on-treatment/ER expression pre-treatment). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Ki-67 | Baseline, Day 15 | Tumor tissue collected by biopsy is used to determine Ki-67 expression. It is measured by IHC and the Ki-67 index is defined as the percent of cells staining positive by validated central assay. Percent change in Ki-67 index was defined as 100\*(Ki-67 index on-treatment - Ki-67 index pre-treatment)/(Ki-67 index pre-treatment). Geometric mean percent change and 90 percent (%) confidence interval for percent change were obtained from a t-test of the log ratio i.e. log(Ki-67 index on-treatment/Ki-67 index pre-treatment). |
| Percent Change From Baseline in Progesterone Receptor (PR) Expression | Baseline, Day 15 | Tumor tissue collected by biopsy is used to determine PR expression. PR expression is measured by IHC and quantified by H-score. The H-score was calculated as the sum of multiplying the tumor cell ER staining intensity level 0 to 3 (0=none, 1=low, 2=moderate, 3=high) by the percentage (0 to 100) of cells at each intensity. Total PR H-score ranged from 0 to 300, where a higher score indicated stronger PR expression. Percent change in PR expression was defined as 100\*(PR expression on-treatment - PR expression pre-treatment)/(PR expression pre-treatment). Geometric mean percent change and 90 percent (%) confidence interval for percent change were obtained from a t-test of the log ratio i.e. log(PR expression on-treatment/PR expression pre-treatment). |
| Pharmacokinetics (PK): Plasma Concentration of LY3484356 | Day 1: 3.5 hours (h) postdose; Day 8: Predose; Day 8: 3.5 h postdose | Plasma Concentration of LY3484356 evaluated using sparse sampling methodology |
Countries
Belgium, France, Germany, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 200 mg LY3484356 Participants received 200 mg LY3484356 administered orally once daily for 15 days | 28 |
| 400 mg LY3484356 Participants received 400 mg LY3484356 administered orally once daily for 15 days | 30 |
| 800 mg LY3484356 Participants received 800 mg LY3484356 administered orally once daily for 15 days | 28 |
| Total | 86 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Protocol Deviation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | 200 mg LY3484356 | Total | 800 mg LY3484356 | 400 mg LY3484356 |
|---|---|---|---|---|
| Age, Continuous | 63.0 years | 63.5 years | 64.0 years | 63.5 years |
| Estrogen Receptor (ER) Expression | 256.82 H-score STANDARD_DEVIATION 42.33 | 281.07 H-score STANDARD_DEVIATION 30.35 | 292.5 H-score STANDARD_DEVIATION 13.36 | 289.81 H-score STANDARD_DEVIATION 17.18 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 8 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) White | 27 Participants | 77 Participants | 23 Participants | 27 Participants |
| Region of Enrollment Belgium | 6 Participants | 19 Participants | 7 Participants | 6 Participants |
| Region of Enrollment France | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Germany | 5 Participants | 18 Participants | 6 Participants | 7 Participants |
| Region of Enrollment Spain | 6 Participants | 28 Participants | 9 Participants | 13 Participants |
| Region of Enrollment United Kingdom | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 10 Participants | 18 Participants | 5 Participants | 3 Participants |
| Sex: Female, Male Female | 28 Participants | 86 Participants | 28 Participants | 30 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 30 | 0 / 28 |
| other Total, other adverse events | 15 / 28 | 12 / 30 | 15 / 28 |
| serious Total, serious adverse events | 1 / 28 | 2 / 30 | 1 / 28 |
Outcome results
Primary
Percent Change From Baseline in Estrogen Receptor (ER) Expression
Tumor tissue collected by biopsy is used to determine ER expression. ER expression is measured by immunohistochemistry (IHC) and quantified by H-score. The H-score was calculated as the sum of multiplying the tumor cell ER staining intensity level 0 to 3 (0=none, 1=low, 2=moderate, 3=high) by the percentage (0 to 100) of cells at each intensity. Total ER H-score ranged from 0 to 300, where a higher score indicated stronger ER expression. Percent change in ER expression was defined as 100\*(ER expression on-treatment - ER expression pre-treatment)/(ER expression pre-treatment). Geometric mean percent change and 90 percent (%) confidence interval for percent change were obtained from a t-test of the log ratio i.e. log(ER expression on-treatment/ER expression pre-treatment).
Time frame: Baseline, Day 15
Population: All enrolled participants with analyzable baseline and posttreatment data.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 200 mg LY3484356 | Percent Change From Baseline in Estrogen Receptor (ER) Expression | -88.89 percent change |
| 400 mg LY3484356 | Percent Change From Baseline in Estrogen Receptor (ER) Expression | -81.50 percent change |
| 800 mg LY3484356 | Percent Change From Baseline in Estrogen Receptor (ER) Expression | -70.13 percent change |
Secondary
Percent Change From Baseline in Ki-67
Tumor tissue collected by biopsy is used to determine Ki-67 expression. It is measured by IHC and the Ki-67 index is defined as the percent of cells staining positive by validated central assay. Percent change in Ki-67 index was defined as 100\*(Ki-67 index on-treatment - Ki-67 index pre-treatment)/(Ki-67 index pre-treatment). Geometric mean percent change and 90 percent (%) confidence interval for percent change were obtained from a t-test of the log ratio i.e. log(Ki-67 index on-treatment/Ki-67 index pre-treatment).
Time frame: Baseline, Day 15
Population: All enrolled participants with analyzable baseline and posttreatment data.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 200 mg LY3484356 | Percent Change From Baseline in Ki-67 | -68.56 percent change |
| 400 mg LY3484356 | Percent Change From Baseline in Ki-67 | -70.61 percent change |
| 800 mg LY3484356 | Percent Change From Baseline in Ki-67 | -72.28 percent change |
Secondary
Percent Change From Baseline in Progesterone Receptor (PR) Expression
Tumor tissue collected by biopsy is used to determine PR expression. PR expression is measured by IHC and quantified by H-score. The H-score was calculated as the sum of multiplying the tumor cell ER staining intensity level 0 to 3 (0=none, 1=low, 2=moderate, 3=high) by the percentage (0 to 100) of cells at each intensity. Total PR H-score ranged from 0 to 300, where a higher score indicated stronger PR expression. Percent change in PR expression was defined as 100\*(PR expression on-treatment - PR expression pre-treatment)/(PR expression pre-treatment). Geometric mean percent change and 90 percent (%) confidence interval for percent change were obtained from a t-test of the log ratio i.e. log(PR expression on-treatment/PR expression pre-treatment).
Time frame: Baseline, Day 15
Population: All enrolled participants with analyzable baseline and posttreatment data.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 200 mg LY3484356 | Percent Change From Baseline in Progesterone Receptor (PR) Expression | -85.44 percent change |
| 400 mg LY3484356 | Percent Change From Baseline in Progesterone Receptor (PR) Expression | -75.56 percent change |
| 800 mg LY3484356 | Percent Change From Baseline in Progesterone Receptor (PR) Expression | -82.01 percent change |
Secondary
Pharmacokinetics (PK): Plasma Concentration of LY3484356
Plasma Concentration of LY3484356 evaluated using sparse sampling methodology
Time frame: Day 1: 3.5 hours (h) postdose; Day 8: Predose; Day 8: 3.5 h postdose
Population: All enrolled participants who received at least one full dose of study drug and have at least one postbaseline evaluable PK sample.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 200 mg LY3484356 | Pharmacokinetics (PK): Plasma Concentration of LY3484356 | Day 8 (Predose) | 33.0 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 70 |
| 200 mg LY3484356 | Pharmacokinetics (PK): Plasma Concentration of LY3484356 | Day 1 (3.5 h Postdose) | 25.3 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 74 |
| 200 mg LY3484356 | Pharmacokinetics (PK): Plasma Concentration of LY3484356 | Day 8 (3.5 h Postdose) | 55.2 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 58 |
| 400 mg LY3484356 | Pharmacokinetics (PK): Plasma Concentration of LY3484356 | Day 8 (Predose) | 74.3 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 77 |
| 400 mg LY3484356 | Pharmacokinetics (PK): Plasma Concentration of LY3484356 | Day 8 (3.5 h Postdose) | 120 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 63 |
| 400 mg LY3484356 | Pharmacokinetics (PK): Plasma Concentration of LY3484356 | Day 1 (3.5 h Postdose) | 86.9 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 82 |
| 800 mg LY3484356 | Pharmacokinetics (PK): Plasma Concentration of LY3484356 | Day 1 (3.5 h Postdose) | 106 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 107 |
| 800 mg LY3484356 | Pharmacokinetics (PK): Plasma Concentration of LY3484356 | Day 8 (3.5 h Postdose) | 225 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 77 |
| 800 mg LY3484356 | Pharmacokinetics (PK): Plasma Concentration of LY3484356 | Day 8 (Predose) | 99.6 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 87 |