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NCT02983604

GS-5829 in Combination With Fulvestrant or Exemestane in Women With Advanced Estrogen Receptor Positive, HER2 Negative-Breast Cancer

Terminated Phase 1, PHASE2 Results posted Last updated 7 August 2019
What this trial tests

Phase 1, PHASE2 trial testing GS-5829 in Advanced Estrogen Receptor Positive HER2- Breast Cancer in 14 participants. Terminated before completion.

Timeline
10 January 2017
Primary endpoint
19 July 2018
19 July 2018

Quick facts

Lead sponsorGilead Sciences
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment14
Start date10 January 2017
Primary completion19 July 2018
Estimated completion19 July 2018
Sites6 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Gilead Sciences — full company profile →

Who can join

18 and older, female only, with Advanced Estrogen Receptor Positive HER2- Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Phase 1b Dose Escalation: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) Through Day 28 at Each Dose Level of GS-5829 Primary · Baseline up to 28 days

A DLT was a toxicity as defined below: * Grade ≥ 4 neutropenia * Grade ≥ 3 neutropenia with fever * Grade ≥ 3 thrombocytopenia * Grade ≥ 2 bleeding (e.g., gastrointestinal, respiratory, epistaxis, purpura) * Grade ≥ 3 or higher non-hematologic toxicity, except: * Grade 3 nausea or emesis with maximum duration of 48 hours on adequate medical therapy * Grade 3 diarrhea which persists for \< 72 hours in the absence of adequate medical therapy * Grade ≥ 2 non-hematologic treatment-emergent adverse event (TEAE) that in the opinion of the investigator is of potential clinical significance such

GroupValue95% CI
GS-5829 4 mg + Exemestane1
GS-5829 4 mg + Fulvestrant0
GS-5829 6 mg + Fulvestrant0
GS-5829 9 mg + Fulvestrant0
Phase 1b Dose Escalation: Pharmacokinetic (PK) Parameter: Cmax of GS-5829 Secondary · Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Days 1 and 15

Cmax is defined as the maximum observed concentration of drug.

Day 1
GroupValue95% CI
GS-5829 4 mg + Exemestane318.25± 107.844
GS-5829 4 mg + Fulvestrant247.00± 3.464
GS-5829 6 mg + Fulvestrant244.00± 9.000
GS-5829 9 mg + Fulvestrant518.00± 60.811
Day 15
GroupValue95% CI
GS-5829 4 mg + Exemestane389.666± 105.6424
GS-5829 4 mg + Fulvestrant370.333± 52.5483
GS-5829 6 mg + Fulvestrant375.666± 67.0919
GS-5829 9 mg + Fulvestrant634.000± 46.6690
Phase 1b Dose Escalation: PK Parameter: AUCtau of GS-5829 Secondary · Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Day 15

AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

GroupValue95% CI
GS-5829 4 mg + Exemestane4989.809± 1655.8737
GS-5829 4 mg + Fulvestrant5218.820± 1326.2407
GS-5829 6 mg + Fulvestrant3937.709± 667.4396
GS-5829 9 mg + Fulvestrant7638.847± 938.3444

Adverse events — posted to ClinicalTrials.gov

Time frame: First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

GS-5829 4 mg + Exemestane
Serious: 1/4 (25%)
Deaths: 0/4
GS-5829 4 mg + Fulvestrant
Serious: 0/3 (0%)
Deaths: 0/3
GS-5829 6 mg + Fulvestrant
Serious: 2/3 (67%)
Deaths: 0/3
GS-5829 9 mg + Fulvestrant
Serious: 0/3 (0%)
Deaths: 0/3

Serious adverse events (5 terms)

ReactionSystemGS-5829 4 mg + ExemestaneGS-5829 4 mg + FulvestrantGS-5829 6 mg + FulvestrantGS-5829 9 mg + Fulvestrant
DysphagiaGastrointestinal disorders
AstheniaGeneral disorders
DehydrationMetabolism and nutrition disorders
HypercalcaemiaMetabolism and nutrition disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Other adverse events (64 terms — click to expand)

ReactionSystemGS-5829 4 mg + ExemestaneGS-5829 4 mg + FulvestrantGS-5829 6 mg + FulvestrantGS-5829 9 mg + Fulvestrant
NauseaGastrointestinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
FatigueGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
DysgeusiaNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
Abdominal distensionGastrointestinal disorders
Abdominal painGastrointestinal disorders
Abdominal tendernessGastrointestinal disorders
ConstipationGastrointestinal disorders
Dry mouthGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
Irritable bowel syndromeGastrointestinal disorders
Oral painGastrointestinal disorders
Salivary hypersecretionGastrointestinal disorders
AstheniaGeneral disorders
Gait disturbanceGeneral disorders
Influenza like illnessGeneral disorders
Injection site bruisingGeneral disorders
PyrexiaGeneral disorders
HyperbilirubinaemiaHepatobiliary disorders
CellulitisInfections and infestations
Fungal skin infectionInfections and infestations
Gastroenteritis viralInfections and infestations
Herpes zosterInfections and infestations
Oral candidiasisInfections and infestations
Oral infectionInfections and infestations
PharyngitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
Viral infectionInfections and infestations
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Platelet count decreasedInvestigations
Weight decreasedInvestigations

Most-reported serious reactions: Dysphagia, Asthenia, Dehydration, Hypercalcaemia, Dyspnoea.

Data from ClinicalTrials.gov NCT02983604 adverse events section.

Sponsor's own description

The primary objectives of the Phase 1b Dose Escalation part of this study are to characterize the safety and tolerability of GS-5829 in combination with exemestane or fulvestrant and to determine the maximum tolerated dose (MTD) or the recommended Phase 2 dose of GS-5829 in combination with fulvestrant in women with advanced estrogen receptor positive, HER2-negative (ER+/HER2-) breast cancer. The primary objective of the Randomized Phase 2 Dose Expansion portion of this study is to evaluate the efficacy of GS-5829 in combination with fulvestrant compared to fulvestrant alone in women with advanced ER+/HER2- breast cancer. This study was terminated early and the Phase 2 portion of the study was not conducted.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Bromodomain and extra-terminal motif inhibitors: a review of preclinical and clinical advances in cancer therapy.
    Alqahtani A, Choucair K, Ashraf M, Hammouda DM, et al · · 2019 · cited 198× · PMID 30906568 · DOI 10.4155/fsoa-2018-0115
  2. Inhibition of BET Proteins and Histone Deacetylase (HDACs): Crossing Roads in Cancer Therapy.
    Manzotti G, Ciarrocchi A, Sancisi V. · · 2019 · cited 60× · PMID 30841549 · DOI 10.3390/cancers11030304
  3. BET Proteins as Attractive Targets for Cancer Therapeutics.
    Sarnik J, Popławski T, Tokarz P. · · 2021 · cited 51× · PMID 34681760 · DOI 10.3390/ijms222011102
  4. Small-molecule agents for cancer immunotherapy.
    Wang F, Fu K, Wang Y, Pan C, et al · · 2024 · cited 41× · PMID 38486980 · DOI 10.1016/j.apsb.2023.12.010
  5. The emerging role of BET inhibitors in breast cancer.
    Andrikopoulou A, Liontos M, Koutsoukos K, Dimopoulos MA, et al · · 2020 · cited 37× · PMID 32827765 · DOI 10.1016/j.breast.2020.08.005
  6. Bromodomain-containing protein 4 (BRD4): a key player in inflammatory bowel disease and potential to inspire epigenetic therapeutics.
    Ma Z, Bolinger AA, Zhou J, Tian B. · · 2023 · cited 21× · PMID 36710583 · DOI 10.1080/14728222.2023.2175317
  7. Role of HOXA9 in solid tumors: mechanistic insights and therapeutic potential.
    Tang L, Peng L, Tan C, Liu H, et al · · 2022 · cited 19× · PMID 36376832 · DOI 10.1186/s12935-022-02767-9
  8. Improved methods for targeting epigenetic reader domains of acetylated and methylated lysine.
    Engelberg IA, Foley CA, James LI, Frye SV. · · 2021 · cited 19× · PMID 33852996 · DOI 10.1016/j.cbpa.2021.03.002

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