Dose Escalation and Expansion Study of GSK525762 in Combination With Fulvestrant in Participants With Hormone Receptor-positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Advanced or Metastatic Breast Cancer

A Phase I/II Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK525762 in Combination With Fulvestrant in Subjects With Hormone Receptor-positive/HER2-negative (HR+/HER2-) Advanced or Metastatic Breast Cancer

Status

Terminated

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02964507

Enrollment

124

Registered

2016-11-16

Start date

2019-09-26

Completion date

2021-07-19

Last updated

2024-08-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Neoplasms

Keywords

GSK525762, HR+/HER2- advanced or metastatic breast cancer, mTPI

Brief summary

This is a combination Phase I and Phase II study, with an aim to evaluate the combination of GSK525762 and fulvestrant in women with HR+/HER2- advanced or metastatic breast cancer, who have disease that has progressed after prior treatment with at least one line of endocrine therapy. The objectives of the study are to first identify, in open-label single-arm Phase I, a recommended Phase II dose of GSK525762 that may be combined safely with fulvestrant. Phase I will follow a modified toxicity probability interval (mTPI) design, and a sentinel group will be evaluated first for dose-limiting toxicity and further expanded to collect additional safety data. This will be followed by a double-blind, randomized controlled Phase II, to identify the clinical activity of the two study treatments when given in combination. The composition of Phase II will be selected at the end of Phase I.

Interventions

DRUGGSK525762

GSK525762 will be administered.

DRUGPlacebo

Placebo will be administered.

DRUGFulvestrant

Fulvestrant will be administered.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Written informed consent provided. * Females 18 years old and greater (at the time of written consent) * Histologically or cytologically confirmed diagnosis of advanced or metastatic adenocarcinoma of the breast. * Documentation of estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive tumor (\>=1% positive stained tumor cell nuclei) based on local testing of the most recent tumor biopsy, using an assay consistent with local standards. * Documentation of HER2-negative tumor based on local testing of the most recent tumor biopsy as per most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. At the time of writing, HER2-negative tumor is defined as immunohistochemistry (IHC) score of 0 or 1+, or negative by in situ hybridization defined as a HER2/chromosome enumeration probe 17 (CEP17) ratio \<2 or for single probe assessment of an average HER2 copy number \<4. * Provision of mandatory screening fresh tumor biopsy sample during the screening period: a. Screening biopsy can be waived if a biopsy was collected within 3 months prior to first dose of study drug and was collected after the last anti-cancer treatment before coming into this study; b. Participants with inaccessible site of biopsy or who have a significant medical risk of obtaining the biopsy should be discussed with the Medical Monitor if they can qualify; c. Bone biopsies are not acceptable. Biopsies should be obtained from bone with metastatic soft-tissue component. Participants with bone only disease may be enrolled upon review by Medical Monitor. * History of prior therapy that satisfies one of the following criteria: a. Aromatase inhibitor (AI) failures: Disease that relapsed during treatment or within 12 months of completion of adjuvant therapy with an AI, OR disease that progressed during treatment with an AI for advanced/metastatic disease. Prior ovarian suppression and/or tamoxifen are allowed as long as other criteria are met; b. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitor plus AI failures: Disease that progressed on a CDK4/6 inhibitor plus AI, for advanced/metastatic disease with a minimum duration of treatment of 12 months (\>=12 months) with CDK4/6 inhibitor plus AI. Participants with either measurable disease or bone only disease are allowed. Prior ovarian suppression and/or tamoxifen are allowed as long as other criteria are met. * Documented progression on last line of systemic anti-cancer therapy with CDK4/6 inhibitor plus AI is required. * Any menopausal status. * Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria is required except for participants with bone only disease. * All prior treatment- related toxicities must be National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4 \<=Grade 1 (except alopecia (permitted at any grade) and peripheral neuropathy (permitted at \<=Grade 2) at the time of treatment allocation. * Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 1. * Adequate organ function. * Able to swallow and retain orally administered medication. * A female participant is eligible to participate if she is of: i) Non-childbearing potential. ii) Child-bearing potential and agrees to use one of the contraception methods. iii) Negative serum pregnancy test \<=7 days prior to first study drug dose. iv) Female participants who are lactating must discontinue nursing prior to the first dose of study treatment and must refrain from nursing throughout the treatment period and for at least 28 days following the last dose of study treatment.

Exclusion criteria

* Prior therapy with any Bromodomain and extra-terminal (BET) inhibitor, any selective estrogen receptor degrader (SERD) including fulvestrant, or inhibitors of the Phosphoinositide-3-kinase (PI3K)/ serine/threonine-specific protein kinase (AKT)/Mammalian Target of Rapamycin (mTOR) pathway. * Prior therapy with more than one line of cytotoxic chemotherapy following diagnosis of advanced/metastatic disease. * More than or equal to 3 lines of systemic anti-cancer therapy in the advanced or metastatic setting. * Recent prior therapy, defined as: a. Any investigational or approved non-biologic anti-cancer drug within 14 days or five half-life (whichever is greater) prior to the first dose of GSK525762 and fulvestrant. b. Any nitrosoureas or mitomycin C within 42 days prior to the first dose of GSK525762 and fulvestrant c. Any anti-cancer biologic agents within 42 days prior to the first dose of GSK525762 and fulvestrant. d. Any radiotherapy within 14 days prior to the first dose of GSK525762 and fulvestrant. If the participant received radiotherapy \<90 days prior to study treatment, the irradiated lesion cannot be the only lesion used for evaluating response. e. Any major surgery within 28 days prior to the first dose of GSK525762 and fulvestrant * Concomitant active malignancy other than HR+/HER2- breast cancer * Therapeutic-dose anticoagulation (e.g., warfarin, low-molecular weight heparin \[LMWH\], or novel oral anticoagulants) must be discontinued and coagulation parameters must be normalized prior to the first dose of GSK525762 and fulvestrant. Prophylactic anticoagulation, with low doses (per standard practice) of agents such as LMWH, direct thrombin inhibitors, or factor Xa inhibitors is permitted. * Current use of a prohibited medication or planned use of any forbidden medications during treatment with GSK525762 and fulvestrant. This includes medications with significant risk of Torsades de pointes as well as those that are potent inducers or inhibitors of Cytochrome P3A4 (CYP3A4) enzymes. * Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal, cardiac disease, or clinically significant bleeding episodes). Any serious and/or unstable pre-existing medical (aside from malignancy), psychiatric disorder, or other conditions that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator. a) Systolic blood pressure higher than 150 millimeters of mercury (mmHg) or diastolic blood pressure higher than 90 mmHg found on 2 separate occasions separated by 1 week, despite adequate therapy, will be defined as uncontrolled hypertension. b) Uncontrolled diabetes mellitus (despite therapeutic; compliance to intervention) as defined by a hemoglobin A1c (HbA1c) level more than 8% and/or occurrence of more than two episodes of ketoacidosis in the 12 months prior to the first dose of study drug. * Participants with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term including participants with massive uncontrolled effusions (pleural, pericardial, peritoneal), pulmonary lymphangitis, and over 50 percent (%) of liver involvement in metastases. * Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. * Cardiac abnormalities as evidenced by any of the following: Baseline QT interval corrected by Fridericia's formula (QTcF) interval \>=480 milliseconds (msec); Clinically significant conduction abnormalities or arrhythmias; Presence of cardiac pacemaker or defibrillator with a paced ventricular rhythm limiting electrocardiogram analysis; History or evidence of current \>=Class II congestive heart failure as defined by New York Heart Association (NYHA); History of acute coronary syndromes (including unstable angina and myocardial infarction), coronary angioplasty, or stenting within the past 3 months. Participants with a history of stent placement requiring ongoing antithrombotic therapy (e.g., clopidogrel, prasugrel) will not be permitted to enroll; Clinically significant cardiomegaly, ventricular hypertrophy, or cardiomyopathy. * Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator assessment). * Presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test result at screening. * History of known human immunodeficiency virus (HIV) infection. * Any serious known immediate or delayed hypersensitivity reaction(s) to GSK525762 or fulvestrant, or idiosyncrasy to drugs chemically related to the investigational drugs. * Hemoptysis \>1 teaspoon in 24 hours within the last 28 days. * Concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) (except for cases where NSAIDs provide benefit over other analgesics and in these cases, consideration should be given to the prophylactic administration of a proton pump inhibitor) and high dose aspirin (allowed up to \<=100 milligrams orally daily). * Participants with history of known bleeding disorder(s) including clinically significant hemorrhage (e.g., gastrointestinal, neurologic), within the past 6 months. * Any clinically significant gastrointestinal abnormalities that may alter absorption, such as malabsorption syndrome, chronic gastrointestinal disease, or major resection of the stomach and/or bowels that could preclude adequate absorption of the study medication.

Design outcomes

Primary

Measure	Time frame	Description
Phase I: Plasma Concentration of GSK525762	Day 1: Pre-dose, 0.5, 1, 3 hours on Weeks 1 and 3; Day 1: Pre-dose, 0.5-1, 4-8 hours on Week 5; Day 1: Pre-dose, 0.5-1 hour on Weeks 9, 17, 25	Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK525762.
Phase II: Progression Free Survival (PFS)	Up to 3 year and 8 months	PFS is defined as the time (in months) from the date of first dose until the date of first documented progressive disease (PD), as assessed by the investigator per RECIST v1.1 criteria, or date of death due to any cause, whichever occurs first. PD is defined as at least a 20% increase in the sum of the diameters of target lesions taking as a reference the smallest sum of diameters for this study.
Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)	Up to 3 year and 8 months	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement or is associated with liver injury and impaired liver function. Any other adverse event apart from SAE is considered as non-SAE.
Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)	Up to 28 days	An event was considered DLT if it occurred within first 28 days of treatment and met one of following DLT criteria: Grade3 or greater neutropenia for \>=5 days, febrile neutropenia, Grade4 anemia of any duration, Grade4 thrombocytopenia of any duration or Grade3 thrombocytopenia with bleeding, alanine aminotransferase (ALT) \>3 times (x) upper limit of normal (ULN)+bilirubin \>=2x ULN (\>35 % direct) or ALT between 3-5xULN with bilirubin \<2xULN but with hepatitis symptoms or rash, Grade3 nausea,vomiting or diarrhea that did not improve within 72hour despite appropriate supportive treatment(s), Grade4 nausea,vomiting,or diarrhea, Grade3 hypertension (uncontrolled despite addition of upto 2 antihypertensive medications), Grade4 hypertension, other Grade3 or greater clinically significant non-hematologic toxicity (including QT duration corrected for heart rate by Fridericia's formula (QTcF), ejection fraction \<lower limit of normal (LLN) with an absolute decrease of \>10% from Baseline.
Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays	Up to 3 year and 8 months	Number of participants with dose reductions and dose interruption or delay due to any reason is presented.
Phase I: Objective Response Rate-Investigator Assessment	Up to 3 year and 8 months	Objective Response Rate is defined as the percentage of participants who demonstrate a Best Response of confirmed complete response (CR) or partial response (PR), as assessed by the investigator per response evaluation criteria in solid tumors (RECIST) version (v) 1.1 criteria.

Secondary

Measure	Time frame	Description
Phase I: Plasma Concentration of Fulvestrant	Day 1: Pre-dose on Weeks 1, 3, 5, 9, 17, 25	Blood samples were collected at indicated time points for PK analysis of Fulvestrant.
Phase II: Overall Survival (OS)	Up to 3 year and 8 months	OS is defined as the interval of time (in months) between the date of first dose and the date of death due to any cause.
Phase II: Disease Control Rate (DCR)	Up to 3 year and 8 months	DCR is defined as the percentage of participants in the population with a confirmed CR, confirmed PR, or SD lasting \>=6 months, as assessed by the investigator per RECIST v1.1 criteria.
Phase II: Plasma Concentration of GSK525762 and GSK3529246	Day 1: Pre-dose, 0.5, 1, 3 hours on Weeks 1 and 3; Day 1: Pre-dose, 0.5-1, 4-8 hours on Week 5, Day 1: Pre-dose, 0.5-1 hour on Weeks 9, 17, 25	Blood samples were planned to be collected for PK analysis of GSK525762 and GSK3529246. GSK3529246 is metabolite of GSK525762.
Phase II: Plasma Concentration of Fulvestrant	Day 1: Pre-dose on Weeks 1, 3, 5, 9, 17, 25	Blood samples were planned to be collected for PK analysis of fulvestrant.
Phase II: Overall Response Rate (ORR)	Up to 3 year and 8 months	ORR is defined as the percentage of participants in the population who demonstrate a BOR of confirmed CR or PR, as assessed by the investigator per RECIST v1.1 criteria.
Phase I: Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment	Up to 4 year and 4 months	Number of participants who withdrew due to toxicity and changes in safety assessment including laboratory parameters and vital signs have been presented.
Phase I: Disease Control Rate (DCR)	Up to 3 year and 8 months	DCR is defined as the percentage of participants in the population with a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) lasting \>=6 months, as assessed by the investigator per RECIST v1.1 criteria.
Phase I: Duration of Response (DoR)	Up to 3 year and 8 months	DoR is defined as the time (in months) from date of first documented evidence of confirmed CR or PR to the date of first documented PD, as assessed by the investigator per RECIST v1.1 criteria, or to the date of death due to any cause among participants with a Best overall response (BOR) of confirmed CR or PR.
Phase I: Progression-free Survival (PFS)	Up to 3 year and 8 months	PFS is defined as the time (in months) from the date of first dose until the date of first documented PD, as assessed by the investigator per RECIST v1.1 criteria, or date of death due to any cause, whichever occurs first. PD is defined as at least a 20% increase in the sum of the diameters of target lesions taking as a reference the smallest sum of diameters for this study.
Phase I: Plasma Concentration of GSK3529246	Day 1: Pre-dose, 0.5, 1, 3 hours on Weeks 1 and 3; Day 1: Pre-dose, 0.5-1, 4-8 hours on Week 5, Day 1: pre-dose, 0.5-1 hour on Weeks 9, 17, 25	Blood samples were collected at indicated time points for PK analysis of GSK3529246. GSK3529246 is an active metabolite of GSK525762.

Other

Measure	Time frame	Description
Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study	Up to 4 year and 4 months	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement or is associated with liver injury and impaired liver function. Any other adverse event apart from SAE is considered as non-SAE. Number of participants with non-serious AEs and SAEs collected from start of the treatment until end of the study were reported.
Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays Until End of the Study	Up to 4 year and 4 months	Number of participants with dose reductions and dose interruption or delay due to any reason is presented. Number of participants with dose reductions and dose interruption or delay due to any reason from start of the treatment until end of the study were reported.

Countries

Australia, Canada, France, South Korea, Spain, United Kingdom, United States

Participant flow

Recruitment details

This was a Phase I/II study of GSK525762 in combination with fulvestrant in participants with hormone receptor-positive/HER2-negative (HR+/HER2-)advanced/metastatic breast cancer. Out of 124 participants enrolled in the study, 1 participant was not treated.

Pre-assignment details

As per study protocol, an interim analysis was conducted during phase 1,following assessment of data,phase 2 was not initiated. However,all existing participants receiving treatment in phase 1 who were considered to be deriving benefit were continued on the study (at investigators decision),until progression or death/withdrawal.As per the protocol the study was considered as completed when the last participant completed/discontinued study treatment and completed the end of treatment visit

Participants by arm

Arm	Count
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure) Participants with aromatose inhibitor (AI) failure received GSK525762 60 milligrams (mg) tablet orally once daily and Fulvestrant (FUL) 500 mg was administered intramuscularly (IM) on days 1, 15, 29, and once monthly thereafter.	33
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M) Participants with Cyclin-Dependent Kinase (CDK4/6)/AI failure within 12 months received GSK525762 60 mg tablet orally once daily and FUL 500 mg was administered IM on days 1, 15, 29, and once monthly thereafter.	12
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M) Participants with CDK4/6/AI failure \>=12 months received GSK525762 60 mg tablet orally once daily and FUL 500 mg was administered IM on days 1, 15, 29, and once monthly thereafter.	42
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease Participants with CDK4/6/AI failure \>=12 months with bone only disease received GSK525762 60 mg tablet orally once daily and FUL 500 mg was administered IM on days 1, 15, 29, and once monthly thereafter.	7
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure) Participants with AI failure received GSK525762 80 mg tablet orally once daily and FUL 500 mg was administered IM on days 1, 15, 29, and once monthly thereafter.	18
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure) Participants with CDK4/6/AI failure received GSK525762 80 mg tablet orally once daily and FUL 500 mg was administered IM on days 1, 15, 29, and once monthly thereafter.	11
Phase II-GSK525762+FUL Participants were planned to receive GSK525762+ FUL. The dose was to be decided based on the totality of the data at the end of Phase I.	0
Phase II-Placebo+FUL Participants were planned to receive Placebo+FUL. The dose was to be decided based on the totality of the data at the end of Phase I.	0
Total	123

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005
Overall Study	Death	11	9	12	2	10	5
Overall Study	Other	3	0	0	0	1	0
Overall Study	Physician Decision	2	0	3	0	1	0
Overall Study	Protocol specified Withdrawal criteria met	0	1	0	0	1	0
Overall Study	Study terminated by Sponsor	9	1	9	3	3	2
Overall Study	Withdrawal by Subject	1	0	1	1	0	1

Baseline characteristics

Characteristic	Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Total	Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase II-Placebo+FUL	Phase II-GSK525762+FUL
Age, Continuous	53.3 Years STANDARD_DEVIATION 8.48	55.7 Years STANDARD_DEVIATION 9.82	58.7 Years STANDARD_DEVIATION 7.97	54.4 Years STANDARD_DEVIATION 8.45	51.5 Years STANDARD_DEVIATION 12.04	56.4 Years STANDARD_DEVIATION 9.8	60.6 Years STANDARD_DEVIATION 9.4	—	—
Race/Ethnicity, Customized Arabic/North African Heritage	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	3 Participants	1 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Black or African American	1 Participants	2 Participants	1 Participants	1 Participants	1 Participants	8 Participants	2 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Central south Asian Heritage	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized East Asian Heritage	2 Participants	8 Participants	1 Participants	6 Participants	2 Participants	26 Participants	7 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Japanese Heritage	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Missing	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Multiple	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized South East Asian Heritage	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	2 Participants	1 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized White/Caucasian/European Heritage	8 Participants	28 Participants	5 Participants	11 Participants	7 Participants	78 Participants	19 Participants	0 Participants	0 Participants
Sex: Female, Male Female	12 Participants	42 Participants	7 Participants	18 Participants	11 Participants	123 Participants	33 Participants	0 Participants	0 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk
deaths Total, all-cause mortality	11 / 33	9 / 12	12 / 42	2 / 7	10 / 18	5 / 11	0 / 0	0 / 0
other Total, other adverse events	33 / 33	12 / 12	42 / 42	7 / 7	18 / 18	11 / 11	0 / 0	0 / 0
serious Total, serious adverse events	5 / 33	1 / 12	10 / 42	3 / 7	6 / 18	2 / 11	0 / 0	0 / 0

Outcome results

Primary

Phase II: Progression Free Survival (PFS)

PFS is defined as the time (in months) from the date of first dose until the date of first documented progressive disease (PD), as assessed by the investigator per RECIST v1.1 criteria, or date of death due to any cause, whichever occurs first. PD is defined as at least a 20% increase in the sum of the diameters of target lesions taking as a reference the smallest sum of diameters for this study.

Time frame: Up to 3 year and 8 months

Population: Modified All Treated Population. Phase II of study was not initiated hence data was not collected and analyzed.

Primary

Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)

An event was considered DLT if it occurred within first 28 days of treatment and met one of following DLT criteria: Grade3 or greater neutropenia for \>=5 days, febrile neutropenia, Grade4 anemia of any duration, Grade4 thrombocytopenia of any duration or Grade3 thrombocytopenia with bleeding, alanine aminotransferase (ALT) \>3 times (x) upper limit of normal (ULN)+bilirubin \>=2x ULN (\>35 % direct) or ALT between 3-5xULN with bilirubin \<2xULN but with hepatitis symptoms or rash, Grade3 nausea,vomiting or diarrhea that did not improve within 72hour despite appropriate supportive treatment(s), Grade4 nausea,vomiting,or diarrhea, Grade3 hypertension (uncontrolled despite addition of upto 2 antihypertensive medications), Grade4 hypertension, other Grade3 or greater clinically significant non-hematologic toxicity (including QT duration corrected for heart rate by Fridericia's formula (QTcF), ejection fraction \<lower limit of normal (LLN) with an absolute decrease of \>10% from Baseline.

Time frame: Up to 28 days

Population: All Treated Population.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)	2 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)	0 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)	1 Participants
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)	1 Participants
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)	0 Participants
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)	2 Participants

Primary

Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays

Number of participants with dose reductions and dose interruption or delay due to any reason is presented.

Time frame: Up to 3 year and 8 months

Population: All Treated Population.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays	Dose reduction	9 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays	Dose interruption/delay	23 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays	Dose reduction	3 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays	Dose interruption/delay	9 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays	Dose reduction	14 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays	Dose interruption/delay	23 Participants
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays	Dose reduction	3 Participants
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays	Dose interruption/delay	4 Participants
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays	Dose reduction	7 Participants
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays	Dose interruption/delay	15 Participants
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays	Dose reduction	8 Participants
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays	Dose interruption/delay	9 Participants

Primary

Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement or is associated with liver injury and impaired liver function. Any other adverse event apart from SAE is considered as non-SAE.

Time frame: Up to 3 year and 8 months

Population: All Treated Population consisted of participants who received at least one dose of study treatment (GSK525762 or fulvestrant).

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)	Non-serious AEs	33 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)	SAEs	5 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)	Non-serious AEs	12 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)	SAEs	1 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)	Non-serious AEs	42 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)	SAEs	10 Participants
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)	Non-serious AEs	7 Participants
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)	SAEs	3 Participants
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)	SAEs	6 Participants
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)	Non-serious AEs	18 Participants
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)	SAEs	2 Participants
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)	Non-serious AEs	11 Participants

Primary

Phase I: Objective Response Rate-Investigator Assessment

Objective Response Rate is defined as the percentage of participants who demonstrate a Best Response of confirmed complete response (CR) or partial response (PR), as assessed by the investigator per response evaluation criteria in solid tumors (RECIST) version (v) 1.1 criteria.

Time frame: Up to 3 year and 8 months

Population: Modified All Treated Population consisted of all participants who received at least one dose of GSK525762 and fulvestrant.

Arm	Measure	Value (NUMBER)
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Objective Response Rate-Investigator Assessment	21 Percentage of participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Objective Response Rate-Investigator Assessment	0 Percentage of participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Objective Response Rate-Investigator Assessment	12 Percentage of participants
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Objective Response Rate-Investigator Assessment	0 Percentage of participants
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Objective Response Rate-Investigator Assessment	17 Percentage of participants
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Objective Response Rate-Investigator Assessment	9 Percentage of participants

Primary

Phase I: Plasma Concentration of GSK525762

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK525762.

Time frame: Day 1: Pre-dose, 0.5, 1, 3 hours on Weeks 1 and 3; Day 1: Pre-dose, 0.5-1, 4-8 hours on Week 5; Day 1: Pre-dose, 0.5-1 hour on Weeks 9, 17, 25

Population: PK Population comprised of participants from the All Treated Population for whom a PK sample was obtained and analyzed. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 5 Day 1, Pre-dose, n=26,9,34,5,14,10	5.804 Nanograms per milliliter	Standard Deviation 7.7777
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 9 Day 1, Pre-dose, n=17,2,23,2,10,4	7.257 Nanograms per milliliter	Standard Deviation 11.2876
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 5 Day 1, 0.5-1 hour, n=24,7,26,3,11,7	640.700 Nanograms per milliliter	Standard Deviation 380.5152
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 5 Day 1, 4-8 hours, n=6,1,9,1,5,0	306.900 Nanograms per milliliter	Standard Deviation 153.8008
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 25 Day 1, 0.5-1 hour, n=5,0,6,2,2,1	418.000 Nanograms per milliliter	Standard Deviation 173.5439
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, 1 hour, n=31,10,40,7,18,10	855.734 Nanograms per milliliter	Standard Deviation 374.3789
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 25 Day 1, Pre-dose, n=9,1,5,2,4,1	34.847 Nanograms per milliliter	Standard Deviation 92.3723
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, 3 hours, n=31,10,39,6,17,10	637.097 Nanograms per milliliter	Standard Deviation 220.5013
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, Pre-dose, n=30,11,41,7,17,11	NA Nanograms per milliliter	—
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 17 Day 1, 0.5-1 hour, n=9,2,9,2,4,1	372.778 Nanograms per milliliter	Standard Deviation 214.7812
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, Pre-dose, n=29,12,31,5,16,8	7.046 Nanograms per milliliter	Standard Deviation 8.2049
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 17 Day 1, Pre-dose, n=11,2,8,2,6,3	9.401 Nanograms per milliliter	Standard Deviation 13.088
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, 0.5 hour, n=28,11,29,4,13,7	766.179 Nanograms per milliliter	Standard Deviation 330.037
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, 1 hour, n=28,11,30,5,13,7	737.536 Nanograms per milliliter	Standard Deviation 310.454
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, 0.5 hour, n=31,11,40,7,17,10	895.466 Nanograms per milliliter	Standard Deviation 520.79
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 9 Day 1, 0.5-1 hour, n=13,1,17,2,6,3	607.408 Nanograms per milliliter	Standard Deviation 528.6891
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, 3 hours, n=28,10,29,5,13,7	423.500 Nanograms per milliliter	Standard Deviation 190.6163
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK525762	Week 5 Day 1, Pre-dose, n=26,9,34,5,14,10	15.251 Nanograms per milliliter	Standard Deviation 18.1145
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, Pre-dose, n=29,12,31,5,16,8	15.797 Nanograms per milliliter	Standard Deviation 20.7736
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, 3 hours, n=31,10,39,6,17,10	526.400 Nanograms per milliliter	Standard Deviation 106.3591
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK525762	Week 25 Day 1, Pre-dose, n=9,1,5,2,4,1	NA Nanograms per milliliter	—
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK525762	Week 17 Day 1, Pre-dose, n=11,2,8,2,6,3	1.365 Nanograms per milliliter	—
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK525762	Week 5 Day 1, 0.5-1 hour, n=24,7,26,3,11,7	463.854 Nanograms per milliliter	Standard Deviation 476.0195
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK525762	Week 9 Day 1, 0.5-1 hour, n=13,1,17,2,6,3	69.400 Nanograms per milliliter	—
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, Pre-dose, n=30,11,41,7,17,11	NA Nanograms per milliliter	—
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK525762	Week 5 Day 1, 4-8 hours, n=6,1,9,1,5,0	145.000 Nanograms per milliliter	—
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, 3 hours, n=28,10,29,5,13,7	447.700 Nanograms per milliliter	Standard Deviation 179.1889
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, 0.5 hour, n=31,11,40,7,17,10	814.364 Nanograms per milliliter	Standard Deviation 465.7197
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK525762	Week 17 Day 1, 0.5-1 hour, n=9,2,9,2,4,1	32.100 Nanograms per milliliter	Standard Deviation 30.2642
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, 1 hour, n=28,11,30,5,13,7	576.427 Nanograms per milliliter	Standard Deviation 298.5082
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, 1 hour, n=31,10,40,7,18,10	828.800 Nanograms per milliliter	Standard Deviation 216.0544
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, 0.5 hour, n=28,11,29,4,13,7	680.936 Nanograms per milliliter	Standard Deviation 435.2668
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK525762	Week 9 Day 1, Pre-dose, n=17,2,23,2,10,4	5.055 Nanograms per milliliter	Standard Deviation 0.7142
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, 1 hour, n=28,11,30,5,13,7	581.073 Nanograms per milliliter	Standard Deviation 273.6803
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, Pre-dose, n=30,11,41,7,17,11	NA Nanograms per milliliter	—
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK525762	Week 17 Day 1, 0.5-1 hour, n=9,2,9,2,4,1	521.241 Nanograms per milliliter	Standard Deviation 404.3103
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK525762	Week 9 Day 1, Pre-dose, n=17,2,23,2,10,4	9.000 Nanograms per milliliter	Standard Deviation 13.3106
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, 3 hours, n=31,10,39,6,17,10	717.769 Nanograms per milliliter	Standard Deviation 293.5412
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, Pre-dose, n=29,12,31,5,16,8	8.598 Nanograms per milliliter	Standard Deviation 13.2639
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK525762	Week 17 Day 1, Pre-dose, n=11,2,8,2,6,3	3.591 Nanograms per milliliter	—
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, 3 hours, n=28,10,29,5,13,7	369.179 Nanograms per milliliter	Standard Deviation 171.4981
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, 0.5 hour, n=28,11,29,4,13,7	504.516 Nanograms per milliliter	Standard Deviation 342.6658
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK525762	Week 5 Day 1, Pre-dose, n=26,9,34,5,14,10	66.527 Nanograms per milliliter	Standard Deviation 198.8847
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, 0.5 hour, n=31,11,40,7,17,10	824.081 Nanograms per milliliter	Standard Deviation 605.1745
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK525762	Week 25 Day 1, 0.5-1 hour, n=5,0,6,2,2,1	380.483 Nanograms per milliliter	Standard Deviation 338.143
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK525762	Week 5 Day 1, 4-8 hours, n=6,1,9,1,5,0	303.000 Nanograms per milliliter	Standard Deviation 177.1489
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK525762	Week 5 Day 1, 0.5-1 hour, n=24,7,26,3,11,7	555.237 Nanograms per milliliter	Standard Deviation 336.1938
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK525762	Week 9 Day 1, 0.5-1 hour, n=13,1,17,2,6,3	445.291 Nanograms per milliliter	Standard Deviation 388.9562
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK525762	Week 25 Day 1, Pre-dose, n=9,1,5,2,4,1	10.198 Nanograms per milliliter	Standard Deviation 10.4909
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, 1 hour, n=31,10,40,7,18,10	947.343 Nanograms per milliliter	Standard Deviation 443.7234
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK525762	Week 9 Day 1, 0.5-1 hour, n=13,1,17,2,6,3	817.000 Nanograms per milliliter	Standard Deviation 287.0854
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, Pre-dose, n=30,11,41,7,17,11	NA Nanograms per milliliter	—
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, 0.5 hour, n=31,11,40,7,17,10	646.251 Nanograms per milliliter	Standard Deviation 537.3585
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, 1 hour, n=31,10,40,7,18,10	634.300 Nanograms per milliliter	Standard Deviation 331.3116
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, 3 hours, n=31,10,39,6,17,10	732.833 Nanograms per milliliter	Standard Deviation 394.366
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, Pre-dose, n=29,12,31,5,16,8	150.410 Nanograms per milliliter	Standard Deviation 295.0514
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, 0.5 hour, n=28,11,29,4,13,7	730.250 Nanograms per milliliter	Standard Deviation 410.6356
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, 1 hour, n=28,11,30,5,13,7	596.800 Nanograms per milliliter	Standard Deviation 134.654
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, 3 hours, n=28,10,29,5,13,7	422.800 Nanograms per milliliter	Standard Deviation 120.6512
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK525762	Week 5 Day 1, Pre-dose, n=26,9,34,5,14,10	15.814 Nanograms per milliliter	Standard Deviation 21.5282
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK525762	Week 5 Day 1, 0.5-1 hour, n=24,7,26,3,11,7	705.667 Nanograms per milliliter	Standard Deviation 208.2218
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK525762	Week 5 Day 1, 4-8 hours, n=6,1,9,1,5,0	431.000 Nanograms per milliliter	—
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK525762	Week 9 Day 1, Pre-dose, n=17,2,23,2,10,4	3.265 Nanograms per milliliter	—
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK525762	Week 17 Day 1, Pre-dose, n=11,2,8,2,6,3	16.850 Nanograms per milliliter	Standard Deviation 2.0506
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK525762	Week 17 Day 1, 0.5-1 hour, n=9,2,9,2,4,1	270.000 Nanograms per milliliter	Standard Deviation 354.9676
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK525762	Week 25 Day 1, Pre-dose, n=9,1,5,2,4,1	10.740 Nanograms per milliliter	Standard Deviation 9.1358
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK525762	Week 25 Day 1, 0.5-1 hour, n=5,0,6,2,2,1	251.350 Nanograms per milliliter	Standard Deviation 225.7792
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, 3 hours, n=31,10,39,6,17,10	831.176 Nanograms per milliliter	Standard Deviation 293.0363
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 9 Day 1, 0.5-1 hour, n=13,1,17,2,6,3	621.867 Nanograms per milliliter	Standard Deviation 440.4829
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 25 Day 1, 0.5-1 hour, n=5,0,6,2,2,1	314.000 Nanograms per milliliter	Standard Deviation 90.5097
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 17 Day 1, 0.5-1 hour, n=9,2,9,2,4,1	640.000 Nanograms per milliliter	Standard Deviation 273.7846
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 9 Day 1, Pre-dose, n=17,2,23,2,10,4	16.469 Nanograms per milliliter	Standard Deviation 23.7102
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, 1 hour, n=31,10,40,7,18,10	1061.722 Nanograms per milliliter	Standard Deviation 397.9207
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, 1 hour, n=28,11,30,5,13,7	875.077 Nanograms per milliliter	Standard Deviation 343.557
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, Pre-dose, n=29,12,31,5,16,8	11.371 Nanograms per milliliter	Standard Deviation 17.845
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 25 Day 1, Pre-dose, n=9,1,5,2,4,1	1.560 Nanograms per milliliter	—
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, Pre-dose, n=30,11,41,7,17,11	NA Nanograms per milliliter	—
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 17 Day 1, Pre-dose, n=11,2,8,2,6,3	7.217 Nanograms per milliliter	Standard Deviation 10.1456
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 5 Day 1, 0.5-1 hour, n=24,7,26,3,11,7	685.773 Nanograms per milliliter	Standard Deviation 446.6621
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, 3 hours, n=28,10,29,5,13,7	471.154 Nanograms per milliliter	Standard Deviation 160.2908
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, 0.5 hour, n=31,11,40,7,17,10	969.265 Nanograms per milliliter	Standard Deviation 659.5862
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 5 Day 1, 4-8 hours, n=6,1,9,1,5,0	352.400 Nanograms per milliliter	Standard Deviation 98.589
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 5 Day 1, Pre-dose, n=26,9,34,5,14,10	14.603 Nanograms per milliliter	Standard Deviation 17.0653
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, 0.5 hour, n=28,11,29,4,13,7	808.846 Nanograms per milliliter	Standard Deviation 548.7639
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, 3 hours, n=31,10,39,6,17,10	782.600 Nanograms per milliliter	Standard Deviation 191.9283
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, Pre-dose, n=30,11,41,7,17,11	NA Nanograms per milliliter	—
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 9 Day 1, Pre-dose, n=17,2,23,2,10,4	6.640 Nanograms per milliliter	Standard Deviation 7.0298
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, 1 hour, n=28,11,30,5,13,7	895.286 Nanograms per milliliter	Standard Deviation 358.3172
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, 0.5 hour, n=28,11,29,4,13,7	917.714 Nanograms per milliliter	Standard Deviation 498.7183
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 9 Day 1, 0.5-1 hour, n=13,1,17,2,6,3	309.627 Nanograms per milliliter	Standard Deviation 375.4223
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, Pre-dose, n=29,12,31,5,16,8	6.799 Nanograms per milliliter	Standard Deviation 5.7108
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 17 Day 1, Pre-dose, n=11,2,8,2,6,3	7.270 Nanograms per milliliter	—
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 3 Day 1, 3 hours, n=28,10,29,5,13,7	523.714 Nanograms per milliliter	Standard Deviation 207.9308
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, 1 hour, n=31,10,40,7,18,10	1069.400 Nanograms per milliliter	Standard Deviation 269.4864
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 17 Day 1, 0.5-1 hour, n=9,2,9,2,4,1	214.000 Nanograms per milliliter	—
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 1 Day 1, 0.5 hour, n=31,11,40,7,17,10	1155.300 Nanograms per milliliter	Standard Deviation 329.8983
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 25 Day 1, 0.5-1 hour, n=5,0,6,2,2,1	186.000 Nanograms per milliliter	—
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 25 Day 1, Pre-dose, n=9,1,5,2,4,1	NA Nanograms per milliliter	—
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 5 Day 1, 0.5-1 hour, n=24,7,26,3,11,7	457.229 Nanograms per milliliter	Standard Deviation 301.9096
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK525762	Week 5 Day 1, Pre-dose, n=26,9,34,5,14,10	77.465 Nanograms per milliliter	Standard Deviation 217.4469

Secondary

Phase I: Disease Control Rate (DCR)

DCR is defined as the percentage of participants in the population with a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) lasting \>=6 months, as assessed by the investigator per RECIST v1.1 criteria.

Time frame: Up to 3 year and 8 months

Population: Modified All Treated Population.

Arm	Measure	Value (NUMBER)
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Disease Control Rate (DCR)	36 Percentage of participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Disease Control Rate (DCR)	0 Percentage of participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Disease Control Rate (DCR)	17 Percentage of participants
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Disease Control Rate (DCR)	14 Percentage of participants
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Disease Control Rate (DCR)	28 Percentage of participants
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Disease Control Rate (DCR)	9 Percentage of participants

Secondary

Phase I: Duration of Response (DoR)

DoR is defined as the time (in months) from date of first documented evidence of confirmed CR or PR to the date of first documented PD, as assessed by the investigator per RECIST v1.1 criteria, or to the date of death due to any cause among participants with a Best overall response (BOR) of confirmed CR or PR.

Time frame: Up to 3 year and 8 months

Population: Modified All Treated Population. Only those participants with a BOR of confirmed CR or PR based on RECIST v1.1 were analyzed hence N=0 for Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure \<12M) and Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure\>=12M Bone Only Disease arms.

Arm	Measure	Value (MEDIAN)
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Duration of Response (DoR)	13.1 Months
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Duration of Response (DoR)	5.8 Months
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Duration of Response (DoR)	14.0 Months
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Duration of Response (DoR)	4.3 Months

Secondary

Phase II: Disease Control Rate (DCR)

DCR is defined as the percentage of participants in the population with a confirmed CR, confirmed PR, or SD lasting \>=6 months, as assessed by the investigator per RECIST v1.1 criteria.

Time frame: Up to 3 year and 8 months

Population: Modified All Treated Population. Phase II of study was not initiated hence data was not collected and analyzed.

Secondary

Phase II: Overall Response Rate (ORR)

ORR is defined as the percentage of participants in the population who demonstrate a BOR of confirmed CR or PR, as assessed by the investigator per RECIST v1.1 criteria.

Time frame: Up to 3 year and 8 months

Population: Modified All Treated Population. Phase II of study was not initiated hence data was not collected and analyzed.

Secondary

Phase II: Overall Survival (OS)

OS is defined as the interval of time (in months) between the date of first dose and the date of death due to any cause.

Time frame: Up to 3 year and 8 months

Population: Modified All Treated Population. Phase II of study was not initiated hence data was not collected and analyzed.

Secondary

Phase II: Plasma Concentration of Fulvestrant

Blood samples were planned to be collected for PK analysis of fulvestrant.

Time frame: Day 1: Pre-dose on Weeks 1, 3, 5, 9, 17, 25

Population: PK Population. Phase II of study was not initiated hence data was not collected and analyzed.

Secondary

Phase II: Plasma Concentration of GSK525762 and GSK3529246

Blood samples were planned to be collected for PK analysis of GSK525762 and GSK3529246. GSK3529246 is metabolite of GSK525762.

Time frame: Day 1: Pre-dose, 0.5, 1, 3 hours on Weeks 1 and 3; Day 1: Pre-dose, 0.5-1, 4-8 hours on Week 5, Day 1: Pre-dose, 0.5-1 hour on Weeks 9, 17, 25

Population: PK Population. Phase II of study was not initiated hence data was not collected and analyzed.

Secondary

Phase I: Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment

Number of participants who withdrew due to toxicity and changes in safety assessment including laboratory parameters and vital signs have been presented.

Time frame: Up to 4 year and 4 months

Population: All Treated Population.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment	6 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment	0 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment	6 Participants
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment	2 Participants
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment	1 Participants
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment	2 Participants

Secondary

Phase I: Plasma Concentration of Fulvestrant

Blood samples were collected at indicated time points for PK analysis of Fulvestrant.

Time frame: Day 1: Pre-dose on Weeks 1, 3, 5, 9, 17, 25

Population: PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of Fulvestrant	Week 1 Day 1, Pre-dose, n=30,11,40,6,17,11	NA Nanograms per milliliter	—
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of Fulvestrant	Week 3 Day 1, Pre-dose, n=30,11,32,7,16,10	13.32481 Nanograms per milliliter	Standard Deviation 6.603131
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of Fulvestrant	Week 5 Day 1, Pre-dose, n=25,9,31,5,16,10	19.82642 Nanograms per milliliter	Standard Deviation 6.917439
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of Fulvestrant	Week 9 Day 1, Pre-dose, n=19,3,19,1,10,5	16.33764 Nanograms per milliliter	Standard Deviation 5.71939
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of Fulvestrant	Week 17 Day 1, Pre-dose, n=15,2,6,1,6,3	16.70103 Nanograms per milliliter	Standard Deviation 5.82639
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of Fulvestrant	Week 25 Day 1, Pre-dose, n=10,1,4,1,4,1	18.07473 Nanograms per milliliter	Standard Deviation 5.933472
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of Fulvestrant	Week 3 Day 1, Pre-dose, n=30,11,32,7,16,10	9.42742 Nanograms per milliliter	Standard Deviation 3.584881
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of Fulvestrant	Week 9 Day 1, Pre-dose, n=19,3,19,1,10,5	13.05750 Nanograms per milliliter	Standard Deviation 4.266495
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of Fulvestrant	Week 25 Day 1, Pre-dose, n=10,1,4,1,4,1	14.21220 Nanograms per milliliter	—
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of Fulvestrant	Week 1 Day 1, Pre-dose, n=30,11,40,6,17,11	NA Nanograms per milliliter	—
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of Fulvestrant	Week 5 Day 1, Pre-dose, n=25,9,31,5,16,10	14.72467 Nanograms per milliliter	Standard Deviation 3.338039
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of Fulvestrant	Week 17 Day 1, Pre-dose, n=15,2,6,1,6,3	20.63475 Nanograms per milliliter	Standard Deviation 7.753497
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of Fulvestrant	Week 25 Day 1, Pre-dose, n=10,1,4,1,4,1	18.60548 Nanograms per milliliter	Standard Deviation 5.300211
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of Fulvestrant	Week 17 Day 1, Pre-dose, n=15,2,6,1,6,3	13.62853 Nanograms per milliliter	Standard Deviation 1.53693
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of Fulvestrant	Week 9 Day 1, Pre-dose, n=19,3,19,1,10,5	13.98242 Nanograms per milliliter	Standard Deviation 4.138764
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of Fulvestrant	Week 5 Day 1, Pre-dose, n=25,9,31,5,16,10	16.51574 Nanograms per milliliter	Standard Deviation 5.957079
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of Fulvestrant	Week 1 Day 1, Pre-dose, n=30,11,40,6,17,11	NA Nanograms per milliliter	—
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of Fulvestrant	Week 3 Day 1, Pre-dose, n=30,11,32,7,16,10	12.44415 Nanograms per milliliter	Standard Deviation 5.669148
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of Fulvestrant	Week 9 Day 1, Pre-dose, n=19,3,19,1,10,5	20.43840 Nanograms per milliliter	—
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of Fulvestrant	Week 3 Day 1, Pre-dose, n=30,11,32,7,16,10	11.34839 Nanograms per milliliter	Standard Deviation 2.085675
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of Fulvestrant	Week 5 Day 1, Pre-dose, n=25,9,31,5,16,10	15.35394 Nanograms per milliliter	Standard Deviation 5.395372
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of Fulvestrant	Week 25 Day 1, Pre-dose, n=10,1,4,1,4,1	19.05100 Nanograms per milliliter	—
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of Fulvestrant	Week 17 Day 1, Pre-dose, n=15,2,6,1,6,3	12.59940 Nanograms per milliliter	—
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of Fulvestrant	Week 1 Day 1, Pre-dose, n=30,11,40,6,17,11	NA Nanograms per milliliter	—
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of Fulvestrant	Week 25 Day 1, Pre-dose, n=10,1,4,1,4,1	16.05110 Nanograms per milliliter	Standard Deviation 2.384935
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of Fulvestrant	Week 1 Day 1, Pre-dose, n=30,11,40,6,17,11	NA Nanograms per milliliter	—
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of Fulvestrant	Week 3 Day 1, Pre-dose, n=30,11,32,7,16,10	12.41568 Nanograms per milliliter	Standard Deviation 4.873113
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of Fulvestrant	Week 17 Day 1, Pre-dose, n=15,2,6,1,6,3	12.81337 Nanograms per milliliter	Standard Deviation 3.550671
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of Fulvestrant	Week 9 Day 1, Pre-dose, n=19,3,19,1,10,5	11.10370 Nanograms per milliliter	Standard Deviation 2.864192
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of Fulvestrant	Week 5 Day 1, Pre-dose, n=25,9,31,5,16,10	16.87293 Nanograms per milliliter	Standard Deviation 8.018589
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of Fulvestrant	Week 9 Day 1, Pre-dose, n=19,3,19,1,10,5	11.84244 Nanograms per milliliter	Standard Deviation 4.615995
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of Fulvestrant	Week 5 Day 1, Pre-dose, n=25,9,31,5,16,10	13.83940 Nanograms per milliliter	Standard Deviation 4.449118
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of Fulvestrant	Week 17 Day 1, Pre-dose, n=15,2,6,1,6,3	16.33830 Nanograms per milliliter	Standard Deviation 4.410823
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of Fulvestrant	Week 3 Day 1, Pre-dose, n=30,11,32,7,16,10	10.25047 Nanograms per milliliter	Standard Deviation 3.121508
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of Fulvestrant	Week 1 Day 1, Pre-dose, n=30,11,40,6,17,11	NA Nanograms per milliliter	—
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of Fulvestrant	Week 25 Day 1, Pre-dose, n=10,1,4,1,4,1	12.24970 Nanograms per milliliter	—

Secondary

Phase I: Plasma Concentration of GSK3529246

Blood samples were collected at indicated time points for PK analysis of GSK3529246. GSK3529246 is an active metabolite of GSK525762.

Time frame: Day 1: Pre-dose, 0.5, 1, 3 hours on Weeks 1 and 3; Day 1: Pre-dose, 0.5-1, 4-8 hours on Week 5, Day 1: pre-dose, 0.5-1 hour on Weeks 9, 17, 25

Population: PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 5 Day 1, 0.5-1 hour, n=24,7,26,3,11,7	270.979 Nanograms per milliliter	Standard Deviation 153.7445
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 5 Day 1, Pre-dose, n=26,9,34,5,14,10	37.480 Nanograms per milliliter	Standard Deviation 32.2441
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, 1 hour, n=28,11,30,5,13,7	414.143 Nanograms per milliliter	Standard Deviation 118.8203
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, 3 hours, n=28,10,29,5,13,7	369.821 Nanograms per milliliter	Standard Deviation 85.0124
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 17 Day 1, 0.5-1 hour, n=9,2,9,2,4,1	189.422 Nanograms per milliliter	Standard Deviation 146.0021
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, 1 hour, n=31,11,41,7,18,10	249.793 Nanograms per milliliter	Standard Deviation 128.567
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 25 Day 1, 0.5-1 hour, n=5,0,6,2,2,1	203.160 Nanograms per milliliter	Standard Deviation 192.2849
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 17 Day 1, Pre-dose, n=11,2,8,2,6,3	41.445 Nanograms per milliliter	Standard Deviation 35.8541
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 9 Day 1, 0.5-1 hour, n=13,1,17,2,6,3	244.162 Nanograms per milliliter	Standard Deviation 189.0153
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, 3 hours, n=31,11,39,6,17,10	276.516 Nanograms per milliliter	Standard Deviation 67.1798
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 9 Day 1, Pre-dose, n=17,2,23,2,10,4	31.041 Nanograms per milliliter	Standard Deviation 28.3504
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, Pre-dose, n=30,11,41,7,17,11	NA Nanograms per milliliter	—
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, Pre-dose, n=29,12,31,5,16,8	37.972 Nanograms per milliliter	Standard Deviation 31.9814
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 25 Day 1, Pre-dose, n=9,1,5,2,4,1	65.756 Nanograms per milliliter	Standard Deviation 125.0011
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 5 Day 1, 4-8 hours, n=6,1,9,1,5,0	263.833 Nanograms per milliliter	Standard Deviation 52.9619
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, 0.5 hour, n=28,11,30,4,13,7	290.482 Nanograms per milliliter	Standard Deviation 155.8106
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, 0.5 hour, n=31,11,39, 7,17,10	174.474 Nanograms per milliliter	Standard Deviation 143.3693
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK3529246	Week 5 Day 1, Pre-dose, n=26,9,34,5,14,10	41.600 Nanograms per milliliter	Standard Deviation 24.1873
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, 0.5 hour, n=28,11,30,4,13,7	243.736 Nanograms per milliliter	Standard Deviation 130.565
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, Pre-dose, n=29,12,31,5,16,8	58.708 Nanograms per milliliter	Standard Deviation 64.1009
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, 1 hour, n=28,11,30,5,13,7	294.573 Nanograms per milliliter	Standard Deviation 102.1516
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, 0.5 hour, n=31,11,39, 7,17,10	126.818 Nanograms per milliliter	Standard Deviation 84.5894
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, 3 hours, n=28,10,29,5,13,7	341.500 Nanograms per milliliter	Standard Deviation 95.5118
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, 3 hours, n=31,11,39,6,17,10	216.364 Nanograms per milliliter	Standard Deviation 50.0685
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, Pre-dose, n=30,11,41,7,17,11	NA Nanograms per milliliter	—
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK3529246	Week 17 Day 1, 0.5-1 hour, n=9,2,9,2,4,1	71.800 Nanograms per milliliter	Standard Deviation 66.7509
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK3529246	Week 25 Day 1, Pre-dose, n=9,1,5,2,4,1	30.100 Nanograms per milliliter	—
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK3529246	Week 17 Day 1, Pre-dose, n=11,2,8,2,6,3	21.450 Nanograms per milliliter	Standard Deviation 5.4447
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK3529246	Week 9 Day 1, Pre-dose, n=17,2,23,2,10,4	33.850 Nanograms per milliliter	Standard Deviation 19.4454
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, 1 hour, n=31,11,41,7,18,10	205.364 Nanograms per milliliter	Standard Deviation 70.6856
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK3529246	Week 5 Day 1, 0.5-1 hour, n=24,7,26,3,11,7	237.614 Nanograms per milliliter	Standard Deviation 211.1272
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK3529246	Week 5 Day 1, 4-8 hours, n=6,1,9,1,5,0	208.000 Nanograms per milliliter	—
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Plasma Concentration of GSK3529246	Week 9 Day 1, 0.5-1 hour, n=13,1,17,2,6,3	36.000 Nanograms per milliliter	—
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK3529246	Week 5 Day 1, 4-8 hours, n=6,1,9,1,5,0	322.778 Nanograms per milliliter	Standard Deviation 166.2354
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, Pre-dose, n=30,11,41,7,17,11	NA Nanograms per milliliter	—
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, 0.5 hour, n=31,11,39, 7,17,10	135.012 Nanograms per milliliter	Standard Deviation 128.9738
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, 1 hour, n=31,11,41,7,18,10	228.597 Nanograms per milliliter	Standard Deviation 118.155
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, 3 hours, n=31,11,39,6,17,10	262.044 Nanograms per milliliter	Standard Deviation 91.2467
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, Pre-dose, n=29,12,31,5,16,8	42.213 Nanograms per milliliter	Standard Deviation 30.7403
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, 0.5 hour, n=28,11,30,4,13,7	195.037 Nanograms per milliliter	Standard Deviation 147.9176
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, 1 hour, n=28,11,30,5,13,7	323.767 Nanograms per milliliter	Standard Deviation 169.5878
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, 3 hours, n=28,10,29,5,13,7	321.404 Nanograms per milliliter	Standard Deviation 131.8554
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK3529246	Week 5 Day 1, Pre-dose, n=26,9,34,5,14,10	56.659 Nanograms per milliliter	Standard Deviation 70.2933
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK3529246	Week 5 Day 1, 0.5-1 hour, n=24,7,26,3,11,7	211.846 Nanograms per milliliter	Standard Deviation 171.4081
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK3529246	Week 9 Day 1, Pre-dose, n=17,2,23,2,10,4	39.323 Nanograms per milliliter	Standard Deviation 40.8779
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK3529246	Week 9 Day 1, 0.5-1 hour, n=13,1,17,2,6,3	178.914 Nanograms per milliliter	Standard Deviation 148.8777
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK3529246	Week 17 Day 1, Pre-dose, n=11,2,8,2,6,3	21.214 Nanograms per milliliter	Standard Deviation 27.8382
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK3529246	Week 17 Day 1, 0.5-1 hour, n=9,2,9,2,4,1	183.671 Nanograms per milliliter	Standard Deviation 149.1568
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK3529246	Week 25 Day 1, Pre-dose, n=9,1,5,2,4,1	49.700 Nanograms per milliliter	Standard Deviation 26.2679
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Plasma Concentration of GSK3529246	Week 25 Day 1, 0.5-1 hour, n=5,0,6,2,2,1	220.367 Nanograms per milliliter	Standard Deviation 195.611
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK3529246	Week 25 Day 1, 0.5-1 hour, n=5,0,6,2,2,1	204.950 Nanograms per milliliter	Standard Deviation 164.1195
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK3529246	Week 9 Day 1, Pre-dose, n=17,2,23,2,10,4	22.700 Nanograms per milliliter	—
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK3529246	Week 5 Day 1, 0.5-1 hour, n=24,7,26,3,11,7	170.800 Nanograms per milliliter	Standard Deviation 66.2851
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, 0.5 hour, n=31,11,39, 7,17,10	115.419 Nanograms per milliliter	Standard Deviation 108.8723
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK3529246	Week 17 Day 1, Pre-dose, n=11,2,8,2,6,3	72.450 Nanograms per milliliter	Standard Deviation 55.9321
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK3529246	Week 25 Day 1, Pre-dose, n=9,1,5,2,4,1	64.500 Nanograms per milliliter	Standard Deviation 60.1041
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, Pre-dose, n=30,11,41,7,17,11	NA Nanograms per milliliter	—
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK3529246	Week 9 Day 1, 0.5-1 hour, n=13,1,17,2,6,3	228.000 Nanograms per milliliter	Standard Deviation 140.0071
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, 1 hour, n=28,11,30,5,13,7	271.200 Nanograms per milliliter	Standard Deviation 145.3227
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, 1 hour, n=31,11,41,7,18,10	175.197 Nanograms per milliliter	Standard Deviation 154.0632
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, 0.5 hour, n=28,11,30,4,13,7	192.275 Nanograms per milliliter	Standard Deviation 149.9568
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, Pre-dose, n=29,12,31,5,16,8	121.820 Nanograms per milliliter	Standard Deviation 190.5127
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK3529246	Week 17 Day 1, 0.5-1 hour, n=9,2,9,2,4,1	129.050 Nanograms per milliliter	Standard Deviation 135.6938
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK3529246	Week 5 Day 1, 4-8 hours, n=6,1,9,1,5,0	292.000 Nanograms per milliliter	—
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, 3 hours, n=28,10,29,5,13,7	252.000 Nanograms per milliliter	Standard Deviation 96.1587
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK3529246	Week 5 Day 1, Pre-dose, n=26,9,34,5,14,10	36.620 Nanograms per milliliter	Standard Deviation 26.8511
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, 3 hours, n=31,11,39,6,17,10	243.517 Nanograms per milliliter	Standard Deviation 136.584
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, 0.5 hour, n=28,11,30,4,13,7	256.669 Nanograms per milliliter	Standard Deviation 173.4439
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 5 Day 1, Pre-dose, n=26,9,34,5,14,10	52.243 Nanograms per milliliter	Standard Deviation 44.071
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 25 Day 1, Pre-dose, n=9,1,5,2,4,1	20.508 Nanograms per milliliter	Standard Deviation 29.5669
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 5 Day 1, 0.5-1 hour, n=24,7,26,3,11,7	295.518 Nanograms per milliliter	Standard Deviation 235.4897
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, Pre-dose, n=29,12,31,5,16,8	48.013 Nanograms per milliliter	Standard Deviation 39.6626
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 5 Day 1, 4-8 hours, n=6,1,9,1,5,0	382.400 Nanograms per milliliter	Standard Deviation 98.2588
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, 3 hours, n=31,11,39,6,17,10	365.059 Nanograms per milliliter	Standard Deviation 130.8231
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 9 Day 1, Pre-dose, n=17,2,23,2,10,4	58.890 Nanograms per milliliter	Standard Deviation 62.233
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, 1 hour, n=31,11,41,7,18,10	327.072 Nanograms per milliliter	Standard Deviation 186.8822
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 9 Day 1, 0.5-1 hour, n=13,1,17,2,6,3	283.667 Nanograms per milliliter	Standard Deviation 177.1211
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 17 Day 1, Pre-dose, n=11,2,8,2,6,3	44.483 Nanograms per milliliter	Standard Deviation 48.7589
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, 0.5 hour, n=31,11,39, 7,17,10	202.224 Nanograms per milliliter	Standard Deviation 225.2895
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 17 Day 1, 0.5-1 hour, n=9,2,9,2,4,1	322.500 Nanograms per milliliter	Standard Deviation 237.0787
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, Pre-dose, n=30,11,41,7,17,11	NA Nanograms per milliliter	—
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, 1 hour, n=28,11,30,5,13,7	511.692 Nanograms per milliliter	Standard Deviation 196.3468
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 25 Day 1, 0.5-1 hour, n=5,0,6,2,2,1	121.300 Nanograms per milliliter	Standard Deviation 90.0854
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, 3 hours, n=28,10,29,5,13,7	438.692 Nanograms per milliliter	Standard Deviation 91.5946
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 9 Day 1, Pre-dose, n=17,2,23,2,10,4	69.625 Nanograms per milliliter	Standard Deviation 53.3875
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 25 Day 1, Pre-dose, n=9,1,5,2,4,1	NA Nanograms per milliliter	—
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, 3 hours, n=31,11,39,6,17,10	300.000 Nanograms per milliliter	Standard Deviation 95.1595
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, Pre-dose, n=29,12,31,5,16,8	49.230 Nanograms per milliliter	Standard Deviation 40.3798
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 17 Day 1, 0.5-1 hour, n=9,2,9,2,4,1	301.000 Nanograms per milliliter	—
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, Pre-dose, n=30,11,41,7,17,11	NA Nanograms per milliliter	—
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 5 Day 1, Pre-dose, n=26,9,34,5,14,10	54.231 Nanograms per milliliter	Standard Deviation 57.2752
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, 1 hour, n=28,11,30,5,13,7	441.571 Nanograms per milliliter	Standard Deviation 140.2353
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, 3 hours, n=28,10,29,5,13,7	403.571 Nanograms per milliliter	Standard Deviation 96.7348
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 9 Day 1, 0.5-1 hour, n=13,1,17,2,6,3	161.367 Nanograms per milliliter	Standard Deviation 113.1437
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, 0.5 hour, n=31,11,39, 7,17,10	186.970 Nanograms per milliliter	Standard Deviation 108.3133
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 25 Day 1, 0.5-1 hour, n=5,0,6,2,2,1	76.300 Nanograms per milliliter	—
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 1 Day 1, 1 hour, n=31,11,41,7,18,10	299.100 Nanograms per milliliter	Standard Deviation 92.9043
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 5 Day 1, 0.5-1 hour, n=24,7,26,3,11,7	203.486 Nanograms per milliliter	Standard Deviation 111.2642
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 17 Day 1, Pre-dose, n=11,2,8,2,6,3	84.600 Nanograms per milliliter	Standard Deviation 74.6129
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Plasma Concentration of GSK3529246	Week 3 Day 1, 0.5 hour, n=28,11,30,4,13,7	288.671 Nanograms per milliliter	Standard Deviation 166.5404

Secondary

Phase I: Progression-free Survival (PFS)

PFS is defined as the time (in months) from the date of first dose until the date of first documented PD, as assessed by the investigator per RECIST v1.1 criteria, or date of death due to any cause, whichever occurs first. PD is defined as at least a 20% increase in the sum of the diameters of target lesions taking as a reference the smallest sum of diameters for this study.

Time frame: Up to 3 year and 8 months

Population: Modified All Treated Population.

Arm	Measure	Value (MEDIAN)
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Progression-free Survival (PFS)	5.6 Months
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Progression-free Survival (PFS)	1.7 Months
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Progression-free Survival (PFS)	2.1 Months
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Progression-free Survival (PFS)	7.2 Months
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Progression-free Survival (PFS)	4.0 Months
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Progression-free Survival (PFS)	1.8 Months

Other Pre-specified

Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays Until End of the Study

Number of participants with dose reductions and dose interruption or delay due to any reason is presented. Number of participants with dose reductions and dose interruption or delay due to any reason from start of the treatment until end of the study were reported.

Time frame: Up to 4 year and 4 months

Population: All Treated Population.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays Until End of the Study	Dose reduction	9 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays Until End of the Study	Dose interruption/delay	23 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays Until End of the Study	Dose reduction	3 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays Until End of the Study	Dose interruption/delay	9 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays Until End of the Study	Dose reduction	14 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays Until End of the Study	Dose interruption/delay	23 Participants
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays Until End of the Study	Dose reduction	3 Participants
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays Until End of the Study	Dose interruption/delay	4 Participants
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays Until End of the Study	Dose reduction	7 Participants
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays Until End of the Study	Dose interruption/delay	15 Participants
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays Until End of the Study	Dose reduction	8 Participants
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays Until End of the Study	Dose interruption/delay	9 Participants

Other Pre-specified

Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study

Time frame: Up to 4 year and 4 months

Population: All Treated Population consisted of participants who received at least one dose of study treatment (GSK525762 or fulvestrant).

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study	Non-serious AEs	33 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study	SAEs	5 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study	Non-serious AEs	12 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study	SAEs	1 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study	Non-serious AEs	42 Participants
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study	SAEs	10 Participants
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study	Non-serious AEs	7 Participants
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study	SAEs	3 Participants
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study	Non-serious AEs	18 Participants
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study	SAEs	6 Participants
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study	Non-serious AEs	11 Participants
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study	SAEs	2 Participants

Source: ClinicalTrials.gov · Data processed: Feb 26, 2026

Dose Escalation and Expansion Study of GSK525762 in Combination With Fulvestrant in Participants With Hormone Receptor-positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Advanced or Metastatic Breast Cancer

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Other

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Phase II: Progression Free Survival (PFS)

Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)

Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays

Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)

Phase I: Objective Response Rate-Investigator Assessment

Phase I: Plasma Concentration of GSK525762

Phase I: Disease Control Rate (DCR)

Phase I: Duration of Response (DoR)

Phase II: Disease Control Rate (DCR)

Phase II: Overall Response Rate (ORR)

Phase II: Overall Survival (OS)

Phase II: Plasma Concentration of Fulvestrant

Phase II: Plasma Concentration of GSK525762 and GSK3529246

Phase I: Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment

Phase I: Plasma Concentration of Fulvestrant

Phase I: Plasma Concentration of GSK3529246

Phase I: Progression-free Survival (PFS)

Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays Until End of the Study

Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study