TerminatedNCT02964507Updated Aug 29, 2024Results posted

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 1 interventional study of GSK525762 and Placebo in Neoplasms, sponsored by GlaxoSmithKline. Terminated at 38 sites in 7 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-08-29.

Sponsored by GlaxoSmithKline · Phase 1, Interventional, and Treatment

Why this study was terminated

This study has been terminated due to meeting protocol defined futility.

Phase: Phase 1
Study type: Interventional
Enrollment: 124
Allocation: Non-randomized
Ages: 18 Years and older
Sex: Female

Study 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.

Conditions studied

Neoplasms

Browse trials for

Keywords

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

In context

Neoplasms

9,610 studies on the registry are indexed under Neoplasms; 2,508 are open to participants now.

This study's enrollment of 124 is above the median of 50 across 7,429 interventional studies indexed under Neoplasms.

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Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,647 studies on the registry; 118 are open to participants now.

Of its 264 completed or terminated interventional studies of FDA-regulated products, 239 (91%) have results posted.

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Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: Female
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 124 participants (actual)

Study arms

Experimental
GSK525762 + Fulvestrant (Phase I)
Drug: GSK525762 · Drug: Fulvestrant
Experimental
GSK525762 + Fulvestrant (Phase II)
Drug: GSK525762 · Drug: Fulvestrant
Placebo comparator
Placebo + Fulvestrant (Phase II)
Drug: Placebo · Drug: Fulvestrant

Interventions

DrugGSK525762
GSK525762 will be administered.
DrugPlacebo
Placebo will be administered.
DrugFulvestrant
Fulvestrant will be administered.

What researchers measure

Primary outcomes

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
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
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
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
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
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

Secondary outcomes

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
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
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
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
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
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
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
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
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
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
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

Other outcomes

Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study
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.
Time frame: Up to 4 year and 4 months
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

Results

Posted Jan 27, 2022

Participant flow

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.

Participant flow — Overall Study
Milestone	Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	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)
Started	33	12	42	7	18	11
Completed	7	1	17	1	2	3
Not completed	26	11	25	6	16	8
Withdrew: Protocol specified withdrawal criteria met	0	1	0	0	1	0
Withdrew: Study terminated by sponsor	9	1	9	3	3	2
Withdrew: Other	3	0	0	0	1	0
Withdrew: Death	11	9	12	2	10	5
Withdrew: Withdrawal by subject	1	0	1	1	0	1
Withdrew: Physician decision	2	0	3	0	1	0

Outcome measures

PrimaryPhase 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
Reported as:: Count of participants · Participants

Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants	Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	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)
Non-serious AEs	33	12	42	7	18	11
SAEs	5	1	10	3	6	2

PrimaryPhase 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
Reported as:: Count of participants · Participants

Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)
Participants	Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	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)
Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)	2	0	1	1	0	2

PrimaryPhase 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
Reported as:: Count of participants · Participants

Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays
Participants	Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	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)
Dose reduction	9	3	14	3	7	8
Dose interruption/delay	23	9	23	4	15	9

PrimaryPhase 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
Reported as:: Number · Percentage of participants

Phase I: Objective Response Rate-Investigator Assessment
Percentage of participants	Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	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)
Phase I: Objective Response Rate-Investigator Assessment	21 (9.0 to 38.9)	0 (0.0 to 26.5)	12 (4.0 to 25.6)	0 (0.0 to 41.0)	17 (3.6 to 41.4)	9 (0.2 to 41.3)

PrimaryPhase 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
Reported as:: Mean · Nanograms per milliliter

Phase I: Plasma Concentration of GSK525762
Nanograms per milliliter	Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	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)
Week 1 Day 1, Pre-dose, n=30,11,41,7,17,11	NA ± NA	NA ± NA	NA ± NA	NA ± NA	NA ± NA	NA ± NA
Week 1 Day 1, 0.5 hour, n=31,11,40,7,17,10	895.466 ± 520.7900	814.364 ± 465.7197	824.081 ± 605.1745	646.251 ± 537.3585	969.265 ± 659.5862	1155.300 ± 329.8983
Week 1 Day 1, 1 hour, n=31,10,40,7,18,10	855.734 ± 374.3789	828.800 ± 216.0544	947.343 ± 443.7234	634.300 ± 331.3116	1061.722 ± 397.9207	1069.400 ± 269.4864
Week 1 Day 1, 3 hours, n=31,10,39,6,17,10	637.097 ± 220.5013	526.400 ± 106.3591	717.769 ± 293.5412	732.833 ± 394.3660	831.176 ± 293.0363	782.600 ± 191.9283
Week 3 Day 1, Pre-dose, n=29,12,31,5,16,8	7.046 ± 8.2049	15.797 ± 20.7736	8.598 ± 13.2639	150.410 ± 295.0514	11.371 ± 17.8450	6.799 ± 5.7108
Week 3 Day 1, 0.5 hour, n=28,11,29,4,13,7	766.179 ± 330.0370	680.936 ± 435.2668	504.516 ± 342.6658	730.250 ± 410.6356	808.846 ± 548.7639	917.714 ± 498.7183
Week 3 Day 1, 1 hour, n=28,11,30,5,13,7	737.536 ± 310.4540	576.427 ± 298.5082	581.073 ± 273.6803	596.800 ± 134.6540	875.077 ± 343.5570	895.286 ± 358.3172
Week 3 Day 1, 3 hours, n=28,10,29,5,13,7	423.500 ± 190.6163	447.700 ± 179.1889	369.179 ± 171.4981	422.800 ± 120.6512	471.154 ± 160.2908	523.714 ± 207.9308
Week 5 Day 1, Pre-dose, n=26,9,34,5,14,10	5.804 ± 7.7777	15.251 ± 18.1145	66.527 ± 198.8847	15.814 ± 21.5282	14.603 ± 17.0653	77.465 ± 217.4469
Week 5 Day 1, 0.5-1 hour, n=24,7,26,3,11,7	640.700 ± 380.5152	463.854 ± 476.0195	555.237 ± 336.1938	705.667 ± 208.2218	685.773 ± 446.6621	457.229 ± 301.9096
Week 5 Day 1, 4-8 hours, n=6,1,9,1,5,0	306.900 ± 153.8008	145.000 ± NA	303.000 ± 177.1489	431.000 ± NA	352.400 ± 98.5890	—
Week 9 Day 1, Pre-dose, n=17,2,23,2,10,4	7.257 ± 11.2876	5.055 ± 0.7142	9.000 ± 13.3106	3.265 ± NA	16.469 ± 23.7102	6.640 ± 7.0298
Week 9 Day 1, 0.5-1 hour, n=13,1,17,2,6,3	607.408 ± 528.6891	69.400 ± NA	445.291 ± 388.9562	817.000 ± 287.0854	621.867 ± 440.4829	309.627 ± 375.4223
Week 17 Day 1, Pre-dose, n=11,2,8,2,6,3	9.401 ± 13.0880	1.365 ± NA	3.591 ± NA	16.850 ± 2.0506	7.217 ± 10.1456	7.270 ± NA
Week 17 Day 1, 0.5-1 hour, n=9,2,9,2,4,1	372.778 ± 214.7812	32.100 ± 30.2642	521.241 ± 404.3103	270.000 ± 354.9676	640.000 ± 273.7846	214.000 ± NA
Week 25 Day 1, Pre-dose, n=9,1,5,2,4,1	34.847 ± 92.3723	NA ± NA	10.198 ± 10.4909	10.740 ± 9.1358	1.560 ± NA	NA ± NA
Week 25 Day 1, 0.5-1 hour, n=5,0,6,2,2,1	418.000 ± 173.5439	—	380.483 ± 338.1430	251.350 ± 225.7792	314.000 ± 90.5097	186.000 ± NA

PrimaryPhase 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

No measurements were reported for this outcome.

SecondaryPhase 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
Reported as:: Count of participants · Participants

Phase I: Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment
Participants	Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	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)
Phase I: Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment	6	0	6	2	1	2

SecondaryPhase 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
Reported as:: Number · Percentage of participants

Phase I: Disease Control Rate (DCR)
Percentage of participants	Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	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)
Phase I: Disease Control Rate (DCR)	36 (20.4 to 54.9)	0 (0.0 to 26.5)	17 (7.0 to 31.4)	14 (0.4 to 57.9)	28 (9.7 to 53.5)	9 (0.2 to 41.3)

SecondaryPhase 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
Reported as:: Median · Months

Phase I: Duration of Response (DoR)
Months	Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	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)
Phase I: Duration of Response (DoR)	13.1 (6.5 to 26.3)	—	5.8 (5.7 to NA)	—	14.0 (5.4 to 16.4)	4.3 (NA to NA)

SecondaryPhase 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
Reported as:: Median · Months

Phase I: Progression-free Survival (PFS)
Months	Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	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)
Phase I: Progression-free Survival (PFS)	5.6 (3.5 to 14.1)	1.7 (1.6 to 2.1)	2.1 (1.7 to 7.1)	7.2 (3.7 to NA)	4.0 (1.8 to 9.4)	1.8 (1.7 to 3.6)

SecondaryPhase 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
Reported as:: Mean · Nanograms per milliliter

Phase I: Plasma Concentration of GSK3529246
Nanograms per milliliter	Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	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)
Week 1 Day 1, Pre-dose, n=30,11,41,7,17,11	NA ± NA	NA ± NA	NA ± NA	NA ± NA	NA ± NA	NA ± NA
Week 1 Day 1, 0.5 hour, n=31,11,39, 7,17,10	174.474 ± 143.3693	126.818 ± 84.5894	135.012 ± 128.9738	115.419 ± 108.8723	202.224 ± 225.2895	186.970 ± 108.3133
Week 1 Day 1, 1 hour, n=31,11,41,7,18,10	249.793 ± 128.5670	205.364 ± 70.6856	228.597 ± 118.1550	175.197 ± 154.0632	327.072 ± 186.8822	299.100 ± 92.9043
Week 1 Day 1, 3 hours, n=31,11,39,6,17,10	276.516 ± 67.1798	216.364 ± 50.0685	262.044 ± 91.2467	243.517 ± 136.5840	365.059 ± 130.8231	300.000 ± 95.1595
Week 3 Day 1, Pre-dose, n=29,12,31,5,16,8	37.972 ± 31.9814	58.708 ± 64.1009	42.213 ± 30.7403	121.820 ± 190.5127	48.013 ± 39.6626	49.230 ± 40.3798
Week 3 Day 1, 0.5 hour, n=28,11,30,4,13,7	290.482 ± 155.8106	243.736 ± 130.5650	195.037 ± 147.9176	192.275 ± 149.9568	256.669 ± 173.4439	288.671 ± 166.5404
Week 3 Day 1, 1 hour, n=28,11,30,5,13,7	414.143 ± 118.8203	294.573 ± 102.1516	323.767 ± 169.5878	271.200 ± 145.3227	511.692 ± 196.3468	441.571 ± 140.2353
Week 3 Day 1, 3 hours, n=28,10,29,5,13,7	369.821 ± 85.0124	341.500 ± 95.5118	321.404 ± 131.8554	252.000 ± 96.1587	438.692 ± 91.5946	403.571 ± 96.7348
Week 5 Day 1, Pre-dose, n=26,9,34,5,14,10	37.480 ± 32.2441	41.600 ± 24.1873	56.659 ± 70.2933	36.620 ± 26.8511	52.243 ± 44.0710	54.231 ± 57.2752
Week 5 Day 1, 0.5-1 hour, n=24,7,26,3,11,7	270.979 ± 153.7445	237.614 ± 211.1272	211.846 ± 171.4081	170.800 ± 66.2851	295.518 ± 235.4897	203.486 ± 111.2642
Week 5 Day 1, 4-8 hours, n=6,1,9,1,5,0	263.833 ± 52.9619	208.000 ± NA	322.778 ± 166.2354	292.000 ± NA	382.400 ± 98.2588	—
Week 9 Day 1, Pre-dose, n=17,2,23,2,10,4	31.041 ± 28.3504	33.850 ± 19.4454	39.323 ± 40.8779	22.700 ± NA	58.890 ± 62.2330	69.625 ± 53.3875
Week 9 Day 1, 0.5-1 hour, n=13,1,17,2,6,3	244.162 ± 189.0153	36.000 ± NA	178.914 ± 148.8777	228.000 ± 140.0071	283.667 ± 177.1211	161.367 ± 113.1437
Week 17 Day 1, Pre-dose, n=11,2,8,2,6,3	41.445 ± 35.8541	21.450 ± 5.4447	21.214 ± 27.8382	72.450 ± 55.9321	44.483 ± 48.7589	84.600 ± 74.6129
Week 17 Day 1, 0.5-1 hour, n=9,2,9,2,4,1	189.422 ± 146.0021	71.800 ± 66.7509	183.671 ± 149.1568	129.050 ± 135.6938	322.500 ± 237.0787	301.000 ± NA
Week 25 Day 1, Pre-dose, n=9,1,5,2,4,1	65.756 ± 125.0011	30.100 ± NA	49.700 ± 26.2679	64.500 ± 60.1041	20.508 ± 29.5669	NA ± NA
Week 25 Day 1, 0.5-1 hour, n=5,0,6,2,2,1	203.160 ± 192.2849	—	220.367 ± 195.6110	204.950 ± 164.1195	121.300 ± 90.0854	76.300 ± NA

SecondaryPhase 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
Reported as:: Mean · Nanograms per milliliter

Phase I: Plasma Concentration of Fulvestrant
Nanograms per milliliter	Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	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)
Week 1 Day 1, Pre-dose, n=30,11,40,6,17,11	NA ± NA	NA ± NA	NA ± NA	NA ± NA	NA ± NA	NA ± NA
Week 3 Day 1, Pre-dose, n=30,11,32,7,16,10	13.32481 ± 6.603131	9.42742 ± 3.584881	12.44415 ± 5.669148	11.34839 ± 2.085675	12.41568 ± 4.873113	10.25047 ± 3.121508
Week 5 Day 1, Pre-dose, n=25,9,31,5,16,10	19.82642 ± 6.917439	14.72467 ± 3.338039	16.51574 ± 5.957079	15.35394 ± 5.395372	16.87293 ± 8.018589	13.83940 ± 4.449118
Week 9 Day 1, Pre-dose, n=19,3,19,1,10,5	16.33764 ± 5.719390	13.05750 ± 4.266495	13.98242 ± 4.138764	20.43840 ± NA	11.10370 ± 2.864192	11.84244 ± 4.615995
Week 17 Day 1, Pre-dose, n=15,2,6,1,6,3	16.70103 ± 5.826390	20.63475 ± 7.753497	13.62853 ± 1.536930	12.59940 ± NA	12.81337 ± 3.550671	16.33830 ± 4.410823
Week 25 Day 1, Pre-dose, n=10,1,4,1,4,1	18.07473 ± 5.933472	14.21220 ± NA	18.60548 ± 5.300211	19.05100 ± NA	16.05110 ± 2.384935	12.24970 ± NA

SecondaryPhase 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

No measurements were reported for this outcome.

SecondaryPhase 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

No measurements were reported for this outcome.

SecondaryPhase 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

No measurements were reported for this outcome.

SecondaryPhase 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

No measurements were reported for this outcome.

SecondaryPhase 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

No measurements were reported for this outcome.

Other pre-specifiedPhase 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
Reported as:: Count of participants · Participants

Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study
Participants	Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	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)
Non-serious AEs	33	12	42	7	18	11
SAEs	5	1	10	3	6	2

Other pre-specifiedPhase 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
Reported as:: Count of participants · Participants

Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays Until End of the Study
Participants	Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	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)
Dose reduction	9	3	14	3	7	8
Dose interruption/delay	23	9	23	4	15	9

Adverse events

Collected over All-cause mortality, serious and non-serious adverse events were collected up to 4 year and 4 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Phase I- GSK525762 60mg+FUL 500mg (AI Failure)	11/33 (33.3%)	5/33 (15.2%)	33/33 (100%)
Phase I-GSK525762 60mg+FUL 500mg (CDK4/6+AI Failure < 12M)	9/12 (75%)	1/12 (8.3%)	12/12 (100%)
Phase I-GSK525762 60mg+FUL 500mg (CDK4/6+AI Failure >=12M)	12/42 (28.6%)	10/42 (23.8%)	42/42 (100%)
Phase I-GSK525762 60mg+FUL 500mg (CDK4/6+AI Failure >=12M Bone Only Disease	2/7 (28.6%)	3/7 (42.9%)	7/7 (100%)
Phase I-GSK525762 80mg+FUL 500mg (AI Failure)	10/18 (55.6%)	6/18 (33.3%)	18/18 (100%)
Phase I-GSK525762 80mg+FUL 500mg (CDK4/6+AI Failure)	5/11 (45.5%)	2/11 (18.2%)	11/11 (100%)
Phase II-GSK525762 +FUL	—	—	—
Phase II-Placebo+FUL	—	—	—

Most frequent serious events

Showing 10 of 33

Most frequent serious events
Event	Phase I- GSK525762 60mg+FUL 500mg (AI Failure)	Phase I-GSK525762 60mg+FUL 500mg (CDK4/6+AI Failure < 12M)	Phase I-GSK525762 60mg+FUL 500mg (CDK4/6+AI Failure >=12M)	Phase I-GSK525762 60mg+FUL 500mg (CDK4/6+AI Failure >=12M Bone Only Disease	Phase I-GSK525762 80mg+FUL 500mg (AI Failure)	Phase I-GSK525762 80mg+FUL 500mg (CDK4/6+AI Failure)	Phase II-GSK525762 +FUL	Phase II-Placebo+FUL
Catheter site haematomaGeneral disorders	0/33	0/12	0/42	1/7	0/18	0/11	—	—
Herpes zosterInfections and infestations	0/33	0/12	0/42	1/7	0/18	0/11	—	—
HypertriglyceridaemiaMetabolism and nutrition disorders	0/33	0/12	0/42	1/7	0/18	0/11	—	—
Supraventricular tachycardiaCardiac disorders	0/33	0/12	0/42	1/7	0/18	0/11	—	—
Decreased appetiteMetabolism and nutrition disorders	0/33	0/12	1/42	0/7	0/18	1/11	—	—
GastritisGastrointestinal disorders	0/33	0/12	0/42	0/7	0/18	1/11	—	—
Microangiopathic haemolytic anaemiaBlood and lymphatic system disorders	0/33	1/12	0/42	0/7	0/18	0/11	—	—
Acute kidney injuryRenal and urinary disorders	0/33	0/12	3/42	0/7	0/18	0/11	—	—
Abdominal pain upperGastrointestinal disorders	0/33	0/12	0/42	0/7	1/18	0/11	—	—
Acute coronary syndromeCardiac disorders	0/33	0/12	0/42	0/7	1/18	0/11	—	—

Most frequent other events

Showing 10 of 68

Most frequent other events
Event	Phase I- GSK525762 60mg+FUL 500mg (AI Failure)	Phase I-GSK525762 60mg+FUL 500mg (CDK4/6+AI Failure < 12M)	Phase I-GSK525762 60mg+FUL 500mg (CDK4/6+AI Failure >=12M)	Phase I-GSK525762 60mg+FUL 500mg (CDK4/6+AI Failure >=12M Bone Only Disease	Phase I-GSK525762 80mg+FUL 500mg (AI Failure)	Phase I-GSK525762 80mg+FUL 500mg (CDK4/6+AI Failure)	Phase II-GSK525762 +FUL	Phase II-Placebo+FUL
DiarrhoeaGastrointestinal disorders	13/33	4/12	20/42	6/7	10/18	4/11	—	—
NauseaGastrointestinal disorders	12/33	7/12	30/42	5/7	11/18	9/11	—	—
FatigueGeneral disorders	19/33	4/12	25/42	1/7	9/18	7/11	—	—
DysgeusiaNervous system disorders	14/33	2/12	25/42	4/7	10/18	7/11	—	—
Blood bilirubin increasedInvestigations	5/33	2/12	8/42	4/7	10/18	2/11	—	—
ThrombocytopeniaBlood and lymphatic system disorders	8/33	4/12	8/42	4/7	3/18	1/11	—	—
ConstipationGastrointestinal disorders	3/33	1/12	6/42	4/7	3/18	4/11	—	—
Decreased appetiteMetabolism and nutrition disorders	14/33	2/12	18/42	3/7	9/18	6/11	—	—
HyperglycaemiaMetabolism and nutrition disorders	13/33	3/12	16/42	3/7	6/18	2/11	—	—
AnaemiaBlood and lymphatic system disorders	4/33	1/12	15/42	3/7	6/18	2/11	—	—

Baseline characteristics

The interim analysis failed to demonstrate clinically meaningful activity, hence Phase II was not initiated.

Age, Continuous
Age, Continuous(Years)	Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	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)	Phase II-GSK525762+FUL	Phase II-Placebo+FUL	Total
Mean	60.6 ± 9.40	53.3 ± 8.48	55.7 ± 9.82	58.7 ± 7.97	54.4 ± 8.45	51.5 ± 12.04	—	—	56.4 ± 9.80

Sex: Female, Male
Sex: Female, Male(Participants)	Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	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)	Phase II-GSK525762+FUL	Phase II-Placebo+FUL	Total
Female	33	12	42	7	18	11	0	0	123
Male	0	0	0	0	0	0	0	0	0

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	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
Central south Asian Heritage	0	0	1	0	0	0	1
East Asian Heritage	7	2	8	1	6	2	26
Japanese Heritage	1	0	0	0	0	0	1
South East Asian Heritage	1	0	0	0	0	1	2
Black or African American	2	1	2	1	1	1	8
Arabic/North African Heritage	1	0	2	0	0	0	3
White/Caucasian/European Heritage	19	8	28	5	11	7	78
Multiple	1	1	0	0	0	0	2
Missing	1	0	1	0	0	0	2

Study locations

38 sites

GSK Investigational Site
Birmingham, Alabama 35249, United States
GSK Investigational Site
Gilbert, Arizona 85234, United States
GSK Investigational Site
Scottsdale, Arizona 85259, United States
GSK Investigational Site
San Diego, California 92123, United States
GSK Investigational Site
Plantation, Florida 33324, United States
GSK Investigational Site
Chicago, Illinois 60611, United States
GSK Investigational Site
New Orleans, Louisiana 70121, United States
GSK Investigational Site
Rochester, Minnesota 55905, United States
GSK Investigational Site
Kansas City, Missouri 64111, United States
GSK Investigational Site
St Louis, Missouri 63110, United States
GSK Investigational Site
The Bronx, New York 10461, United States
GSK Investigational Site
White Plains, New York 10601, United States
GSK Investigational Site
Providence, Rhode Island 02903, United States
GSK Investigational Site
Houston, Texas 77030, United States
GSK Investigational Site
Seattle, Washington 98101, United States
GSK Investigational Site
Port Macquarie, New South Wales 2444, Australia
GSK Investigational Site
Bedford Park, South Australia 5042, Australia
GSK Investigational Site
Heidelberg, Victoria 3084, Australia
GSK Investigational Site
Ottawa, Ontario K1H 8L6, Canada
GSK Investigational Site
Toronto, Ontario M5G 2M9, Canada
GSK Investigational Site
Montreal, Quebec H2L 4M1, Canada
GSK Investigational Site
Montreal, Quebec H3T 1E2, Canada
GSK Investigational Site
Québec, Quebec G1S 4L8, Canada
GSK Investigational Site
Bordeaux, 33076, France
GSK Investigational Site
Saint-Herblain, 44805, France
GSK Investigational Site
Gyeonggi-do, 410-769, South Korea
GSK Investigational Site
Seoul, 120-752, South Korea
GSK Investigational Site
Seoul, 135-710, South Korea
GSK Investigational Site
Seoul, 138-736, South Korea
GSK Investigational Site
A Coruña, 15006, Spain
GSK Investigational Site
Barcelona, 8035, Spain
GSK Investigational Site
Lleida, 25198, Spain
GSK Investigational Site
Manchester, Lancashire M20 4BX, United Kingdom
GSK Investigational Site
Northwood, Middlesex HA6 2RN, United Kingdom
GSK Investigational Site
Nottingham, Nottinghamshire NG5 1PB, United Kingdom
GSK Investigational Site
Glasgow, G12 OYN, United Kingdom
GSK Investigational Site
London, EC1M 6BQ, United Kingdom
GSK Investigational Site
London, NW1 2PG, United Kingdom

References and documents

Study documents

Study protocol · May 6, 2020
Statistical analysis plan · Aug 11, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — GSK will assess requests from qualified researchers for anonymized individual patient-level data (IPD) and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf

Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report

Time frame: Anonymized IPD is made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.

Access criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Data sharing details ↗ · www.gsk-studyregister.com

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 29, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02964507
Lead sponsor: GlaxoSmithKline
Responsible party: Sponsor
First posted: Nov 16, 2016
Start date: Sep 26, 2019
Primary completion: Sep 29, 2020
Completion: Jul 19, 2021
Results posted: Jan 27, 2022
Last update: Aug 29, 2024

Study contacts

GSK Clinical Trials

study director · GlaxoSmithKline

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in Aug 2024. You cannot join it, but the record below documents what was studied.

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