Trial Outcomes & Findings for A Study of LY3484356 in Women With Breast Cancer Before Having Surgery (NCT NCT04647487)
NCT ID: NCT04647487
Last Updated: 2025-11-12
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
87 participants
Primary outcome timeframe
Baseline, Day 15
Results posted on
2025-11-12
Participant Flow
Participant milestones
| Measure |
200 mg LY3484356
Participants received 200 mg LY3484356 administered orally once daily for 15 days
|
400 mg LY3484356
Participants received 400 mg LY3484356 administered orally once daily for 15 days
|
800 mg LY3484356
Participants received 800 mg LY3484356 administered orally once daily for 15 days
|
|---|---|---|---|
|
Overall Study
STARTED
|
28
|
30
|
29
|
|
Overall Study
Received At Least One Dose of Study Drug
|
28
|
30
|
28
|
|
Overall Study
COMPLETED
|
27
|
30
|
26
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
3
|
Reasons for withdrawal
| Measure |
200 mg LY3484356
Participants received 200 mg LY3484356 administered orally once daily for 15 days
|
400 mg LY3484356
Participants received 400 mg LY3484356 administered orally once daily for 15 days
|
800 mg LY3484356
Participants received 800 mg LY3484356 administered orally once daily for 15 days
|
|---|---|---|---|
|
Overall Study
Protocol Deviation
|
0
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
2
|
Baseline Characteristics
All enrolled participants with analyzable baseline and posttreatment data.
Baseline characteristics by cohort
| Measure |
200 mg LY3484356
n=28 Participants
Participants received 200 mg LY3484356 administered orally once daily for 15 days
|
400 mg LY3484356
n=30 Participants
Participants received 400 mg LY3484356 administered orally once daily for 15 days
|
800 mg LY3484356
n=28 Participants
Participants received 800 mg LY3484356 administered orally once daily for 15 days
|
Total
n=86 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
63.0 years
n=28 Participants
|
63.5 years
n=30 Participants
|
64.0 years
n=28 Participants
|
63.5 years
n=86 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=28 Participants
|
30 Participants
n=30 Participants
|
28 Participants
n=28 Participants
|
86 Participants
n=86 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=28 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=28 Participants
|
0 Participants
n=86 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=28 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=28 Participants
|
0 Participants
n=86 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=28 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=28 Participants
|
0 Participants
n=86 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=28 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=28 Participants
|
0 Participants
n=86 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=28 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=28 Participants
|
1 Participants
n=86 Participants
|
|
Race (NIH/OMB)
White
|
27 Participants
n=28 Participants
|
27 Participants
n=30 Participants
|
23 Participants
n=28 Participants
|
77 Participants
n=86 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=28 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=28 Participants
|
0 Participants
n=86 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=28 Participants
|
3 Participants
n=30 Participants
|
5 Participants
n=28 Participants
|
8 Participants
n=86 Participants
|
|
Region of Enrollment
Spain
|
6 Participants
n=28 Participants
|
13 Participants
n=30 Participants
|
9 Participants
n=28 Participants
|
28 Participants
n=86 Participants
|
|
Region of Enrollment
Belgium
|
6 Participants
n=28 Participants
|
6 Participants
n=30 Participants
|
7 Participants
n=28 Participants
|
19 Participants
n=86 Participants
|
|
Region of Enrollment
Germany
|
5 Participants
n=28 Participants
|
7 Participants
n=30 Participants
|
6 Participants
n=28 Participants
|
18 Participants
n=86 Participants
|
|
Region of Enrollment
United States
|
10 Participants
n=28 Participants
|
3 Participants
n=30 Participants
|
5 Participants
n=28 Participants
|
18 Participants
n=86 Participants
|
|
Region of Enrollment
France
|
0 Participants
n=28 Participants
|
1 Participants
n=30 Participants
|
1 Participants
n=28 Participants
|
2 Participants
n=86 Participants
|
|
Region of Enrollment
United Kingdom
|
1 Participants
n=28 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=28 Participants
|
1 Participants
n=86 Participants
|
|
Estrogen Receptor (ER) Expression
|
256.82 H-score
STANDARD_DEVIATION 42.33 • n=22 Participants • All enrolled participants with analyzable baseline and posttreatment data.
|
289.81 H-score
STANDARD_DEVIATION 17.18 • n=27 Participants • All enrolled participants with analyzable baseline and posttreatment data.
|
292.5 H-score
STANDARD_DEVIATION 13.36 • n=26 Participants • All enrolled participants with analyzable baseline and posttreatment data.
|
281.07 H-score
STANDARD_DEVIATION 30.35 • n=75 Participants • All enrolled participants with analyzable baseline and posttreatment data.
|
PRIMARY outcome
Timeframe: Baseline, Day 15Population: All enrolled participants with analyzable baseline and posttreatment data.
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).
Outcome measures
| Measure |
200 mg LY3484356
n=22 Participants
Participants received 200 mg LY3484356 administered orally once daily for 15 days
|
400 mg LY3484356
n=27 Participants
Participants received 400 mg LY3484356 administered orally once daily for 15 days
|
800 mg LY3484356
n=26 Participants
Participants received 800 mg LY3484356 administered orally once daily for 15 days
|
|---|---|---|---|
|
Percent Change From Baseline in Estrogen Receptor (ER) Expression
|
-88.89 percent change
Interval -95.62 to -71.85
|
-81.50 percent change
Interval -91.34 to -60.47
|
-70.13 percent change
Interval -78.38 to -58.75
|
SECONDARY outcome
Timeframe: Baseline, Day 15Population: All enrolled participants with analyzable baseline and posttreatment data.
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).
Outcome measures
| Measure |
200 mg LY3484356
n=21 Participants
Participants received 200 mg LY3484356 administered orally once daily for 15 days
|
400 mg LY3484356
n=22 Participants
Participants received 400 mg LY3484356 administered orally once daily for 15 days
|
800 mg LY3484356
n=20 Participants
Participants received 800 mg LY3484356 administered orally once daily for 15 days
|
|---|---|---|---|
|
Percent Change From Baseline in Ki-67
|
-68.56 percent change
Interval -78.71 to -53.59
|
-70.61 percent change
Interval -80.04 to -56.73
|
-72.28 percent change
Interval -81.22 to -59.09
|
SECONDARY outcome
Timeframe: Baseline, Day 15Population: All enrolled participants with analyzable baseline and posttreatment data.
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).
Outcome measures
| Measure |
200 mg LY3484356
n=20 Participants
Participants received 200 mg LY3484356 administered orally once daily for 15 days
|
400 mg LY3484356
n=26 Participants
Participants received 400 mg LY3484356 administered orally once daily for 15 days
|
800 mg LY3484356
n=26 Participants
Participants received 800 mg LY3484356 administered orally once daily for 15 days
|
|---|---|---|---|
|
Percent Change From Baseline in Progesterone Receptor (PR) Expression
|
-85.44 percent change
Interval -96.61 to -37.36
|
-75.56 percent change
Interval -90.33 to -38.2
|
-82.01 percent change
Interval -91.98 to -59.66
|
SECONDARY outcome
Timeframe: Day 1: 3.5 hours (h) postdose; Day 8: Predose; Day 8: 3.5 h postdosePopulation: All enrolled participants who received at least one full dose of study drug and have at least one postbaseline evaluable PK sample.
Plasma Concentration of LY3484356 evaluated using sparse sampling methodology
Outcome measures
| Measure |
200 mg LY3484356
n=27 Participants
Participants received 200 mg LY3484356 administered orally once daily for 15 days
|
400 mg LY3484356
n=27 Participants
Participants received 400 mg LY3484356 administered orally once daily for 15 days
|
800 mg LY3484356
n=25 Participants
Participants received 800 mg LY3484356 administered orally once daily for 15 days
|
|---|---|---|---|
|
Pharmacokinetics (PK): Plasma Concentration of LY3484356
Day 1 (3.5 h Postdose)
|
25.3 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 74
|
86.9 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 82
|
106 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 107
|
|
Pharmacokinetics (PK): Plasma Concentration of LY3484356
Day 8 (Predose)
|
33.0 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 70
|
74.3 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 77
|
99.6 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 87
|
|
Pharmacokinetics (PK): Plasma Concentration of LY3484356
Day 8 (3.5 h Postdose)
|
55.2 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 58
|
120 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 63
|
225 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 77
|
Adverse Events
200 mg LY3484356
Serious events: 1 serious events
Other events: 15 other events
Deaths: 0 deaths
400 mg LY3484356
Serious events: 2 serious events
Other events: 12 other events
Deaths: 0 deaths
800 mg LY3484356
Serious events: 1 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
200 mg LY3484356
n=28 participants at risk
Participants received 200 mg LY3484356 administered orally once daily for 15 days
|
400 mg LY3484356
n=30 participants at risk
Participants received 400 mg LY3484356 administered orally once daily for 15 days
|
800 mg LY3484356
n=28 participants at risk
Participants received 800 mg LY3484356 administered orally once daily for 15 days
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Post procedural haematoma
|
0.00%
0/28 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
6.7%
2/30 • Number of events 2 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
0.00%
0/28 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
3.6%
1/28 • Number of events 1 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
0.00%
0/30 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
0.00%
0/28 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/28 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
0.00%
0/30 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
3.6%
1/28 • Number of events 1 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
|
Infections and infestations
Mastitis
|
3.6%
1/28 • Number of events 1 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
0.00%
0/30 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
0.00%
0/28 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
Other adverse events
| Measure |
200 mg LY3484356
n=28 participants at risk
Participants received 200 mg LY3484356 administered orally once daily for 15 days
|
400 mg LY3484356
n=30 participants at risk
Participants received 400 mg LY3484356 administered orally once daily for 15 days
|
800 mg LY3484356
n=28 participants at risk
Participants received 800 mg LY3484356 administered orally once daily for 15 days
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
10.7%
3/28 • Number of events 4 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
0.00%
0/30 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
0.00%
0/28 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
10.7%
3/28 • Number of events 4 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
10.0%
3/30 • Number of events 3 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
32.1%
9/28 • Number of events 9 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Nausea
|
10.7%
3/28 • Number of events 3 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
3.3%
1/30 • Number of events 1 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
14.3%
4/28 • Number of events 4 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
|
General disorders
Asthenia
|
0.00%
0/28 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
13.3%
4/30 • Number of events 4 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
3.6%
1/28 • Number of events 1 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
|
General disorders
Fatigue
|
7.1%
2/28 • Number of events 2 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
6.7%
2/30 • Number of events 2 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
10.7%
3/28 • Number of events 6 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.6%
1/28 • Number of events 1 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
3.3%
1/30 • Number of events 1 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
7.1%
2/28 • Number of events 3 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
|
Nervous system disorders
Dizziness
|
7.1%
2/28 • Number of events 2 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
0.00%
0/30 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
0.00%
0/28 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
|
Nervous system disorders
Headache
|
7.1%
2/28 • Number of events 2 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
6.7%
2/30 • Number of events 2 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
7.1%
2/28 • Number of events 4 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
|
Reproductive system and breast disorders
Breast pain
|
7.1%
2/28 • Number of events 4 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
6.7%
2/30 • Number of events 2 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
7.1%
2/28 • Number of events 3 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
7.1%
2/28 • Number of events 2 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
0.00%
0/30 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
3.6%
1/28 • Number of events 1 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
7.1%
2/28 • Number of events 2 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
0.00%
0/30 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
3.6%
1/28 • Number of events 1 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
|
Vascular disorders
Hot flush
|
14.3%
4/28 • Number of events 4 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
6.7%
2/30 • Number of events 2 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
7.1%
2/28 • Number of events 2 • Baseline until end of follow-up (up to 63 days)
All enrolled participants who received at least one dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60