Trial Outcomes & Findings for GS-5829 in Combination With Fulvestrant or Exemestane in Women With Advanced Estrogen Receptor Positive, HER2 Negative-Breast Cancer (NCT NCT02983604)

Last Updated: 2019-08-07

Results Overview

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 that further dose escalation would expose participants to unacceptable risk * Treatment interruption of ≥ 7 days due to unresolved toxicity * Grade 3 or Grade 4 elevation in aspartate transaminase (AST) or alanine transaminase (ALT) associated with a Grade 2 elevation in bilirubin that is at least possibly related to study drug

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

14 participants

Primary outcome timeframe

Baseline up to 28 days

Results posted on

2019-08-07

Participant Flow

Participants were enrolled at study sites in the United States. The first participant was screened on 10 January 2017. The last study visit occurred on 19 July 2018.

17 participants were screened.

Participant milestones

Participant milestones
Measure	GS-5829 4 mg + Exemestane GS-5829 4 mg tablets once daily + exemestane 25 mg tablet once daily	GS-5829 4 mg + Fulvestrant GS-5829 4 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)	GS-5829 6 mg + Fulvestrant GS-5829 6 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)	GS-5829 9 mg + Fulvestrant GS-5829 9 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)
Overall Study STARTED	4	3	4	3
Overall Study COMPLETED	4	3	3	3
Overall Study NOT COMPLETED	0	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	GS-5829 4 mg + Exemestane GS-5829 4 mg tablets once daily + exemestane 25 mg tablet once daily	GS-5829 4 mg + Fulvestrant GS-5829 4 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)	GS-5829 6 mg + Fulvestrant GS-5829 6 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)	GS-5829 9 mg + Fulvestrant GS-5829 9 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)
Overall Study Enrolled but not Treated	0	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GS-5829 4 mg + Exemestane n=4 Participants GS-5829 4 mg tablets once daily + exemestane 25 mg tablet once daily	GS-5829 4 mg + Fulvestrant n=3 Participants GS-5829 4 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)	GS-5829 6 mg + Fulvestrant n=3 Participants GS-5829 6 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)	GS-5829 9 mg + Fulvestrant n=3 Participants GS-5829 9 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)	Total n=13 Participants Total of all reporting groups
Age, Continuous	59.3 years STANDARD_DEVIATION 4.50 • n=93 Participants	61.3 years STANDARD_DEVIATION 7.51 • n=4 Participants	63.0 years STANDARD_DEVIATION 9.54 • n=27 Participants	65.0 years STANDARD_DEVIATION 12.29 • n=483 Participants	61.9 years STANDARD_DEVIATION 7.74 • n=36 Participants
Sex: Female, Male Female	4 Participants n=93 Participants	3 Participants n=4 Participants	3 Participants n=27 Participants	3 Participants n=483 Participants	13 Participants n=36 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=93 Participants	3 Participants n=4 Participants	3 Participants n=27 Participants	3 Participants n=483 Participants	13 Participants n=36 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race/Ethnicity, Customized White	3 Participants n=93 Participants	3 Participants n=4 Participants	3 Participants n=27 Participants	3 Participants n=483 Participants	12 Participants n=36 Participants
Race/Ethnicity, Customized Other	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants

PRIMARY outcome

Timeframe: Baseline up to 28 days

Population: The DLT Analysis Set included all participants in the Safety Analysis Set who completed all treatment and safety procedures through Day 28, inclusive, or experienced a DLT prior to Day 28, exclusive.

Outcome measures

Outcome measures
Measure	GS-5829 4 mg + Exemestane n=3 Participants GS-5829 4 mg tablets once daily + exemestane 25 mg tablet once daily	GS-5829 4 mg + Fulvestrant n=3 Participants GS-5829 4 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)	GS-5829 6 mg + Fulvestrant n=3 Participants GS-5829 6 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)	GS-5829 9 mg + Fulvestrant n=3 Participants GS-5829 9 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)
Phase 1b Dose Escalation: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) Through Day 28 at Each Dose Level of GS-5829	1 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline up to 2 years

Population: As the study was terminated prior to the Phase 2 portion of the study, no participants were enrolled in the Phase 2 portion of the study and data was not collected for this endpoint.

Progression-Free Survival (PFS) was defined as the interval from date of randomization to the earlier of the first documented confirmed disease progression or death from any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Days 1 and 15

Population: The PK Analysis Set included all enrolled participants who received at least 1 dose of study drug and have at least 1 nonmissing postdose concentration value reported by the PK laboratory, excluding participants who received concomitant medications prohibited in this study. Only participants with available data were analyzed.

Cmax is defined as the maximum observed concentration of drug.

Outcome measures

Outcome measures
Measure	GS-5829 4 mg + Exemestane n=4 Participants GS-5829 4 mg tablets once daily + exemestane 25 mg tablet once daily	GS-5829 4 mg + Fulvestrant n=3 Participants GS-5829 4 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)	GS-5829 6 mg + Fulvestrant n=3 Participants GS-5829 6 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)	GS-5829 9 mg + Fulvestrant n=2 Participants GS-5829 9 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)
Phase 1b Dose Escalation: Pharmacokinetic (PK) Parameter: Cmax of GS-5829 Day 1	318.25 ng/mL Standard Deviation 107.844	247.00 ng/mL Standard Deviation 3.464	244.00 ng/mL Standard Deviation 9.000	518.00 ng/mL Standard Deviation 60.811
Phase 1b Dose Escalation: Pharmacokinetic (PK) Parameter: Cmax of GS-5829 Day 15	389.666 ng/mL Standard Deviation 105.6424	370.333 ng/mL Standard Deviation 52.5483	375.666 ng/mL Standard Deviation 67.0919	634.000 ng/mL Standard Deviation 46.6690

SECONDARY outcome

Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Day 15

Population: Participants in the PK Analysis Set with available data were analyzed.

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

Outcome measures

Outcome measures
Measure	GS-5829 4 mg + Exemestane n=3 Participants GS-5829 4 mg tablets once daily + exemestane 25 mg tablet once daily	GS-5829 4 mg + Fulvestrant n=3 Participants GS-5829 4 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)	GS-5829 6 mg + Fulvestrant n=3 Participants GS-5829 6 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)	GS-5829 9 mg + Fulvestrant n=2 Participants GS-5829 9 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)
Phase 1b Dose Escalation: PK Parameter: AUCtau of GS-5829	4989.809 h*ng/mL Standard Deviation 1655.8737	5218.820 h*ng/mL Standard Deviation 1326.2407	3937.709 h*ng/mL Standard Deviation 667.4396	7638.847 h*ng/mL Standard Deviation 938.3444

SECONDARY outcome

Timeframe: Baseline up to 2 years

Population: As the study was terminated prior to the Phase 2 portion of the study, no participants were enrolled in the Phase 2 portion of the study and data was not collected for this endpoint.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to 2 years

Population: As the study was terminated prior to the Phase 2 portion of the study, no participants were enrolled in the Phase 2 portion of the study and data was not collected for this endpoint.

Overall response rate (ORR) was defined as the proportion of participants who achieve complete response (CR) or partial response (PR), based on Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 study progression criteria.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to 2 years

Population: As the study was terminated prior to the Phase 2 portion of the study, no participants were enrolled in the Phase 2 portion of the study and data was not collected for this endpoint.

Clinical benefit rate (CBR) was defined as the proportion of participants who achieve CR, PR, or stable disease that lasts for \> 24 weeks based on RECIST v. 1.1 study progression criteria.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to 2 years

Population: As the study was terminated prior to the Phase 2 portion of the study, no participants were enrolled in the Phase 2 portion of the study and data was not collected for this endpoint.

Overall survival was defined as the interval from date of randomization to date of death from any cause.

Outcome measures

Outcome data not reported

Adverse Events

GS-5829 4 mg + Exemestane

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

GS-5829 4 mg + Fulvestrant

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

GS-5829 6 mg + Fulvestrant

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

GS-5829 9 mg + Fulvestrant

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GS-5829 4 mg + Exemestane n=4 participants at risk GS-5829 4 mg tablets once daily + exemestane 25 mg tablet once daily	GS-5829 4 mg + Fulvestrant n=3 participants at risk GS-5829 4 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)	GS-5829 6 mg + Fulvestrant n=3 participants at risk GS-5829 6 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)	GS-5829 9 mg + Fulvestrant n=3 participants at risk GS-5829 9 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)
Gastrointestinal disorders Dysphagia	0.00% 0/4 • First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.	0.00% 0/3 • First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.	33.3% 1/3 • First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.	0.00% 0/3 • First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.
General disorders Asthenia	25.0% 1/4 • First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.	0.00% 0/3 • First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.	0.00% 0/3 • First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.	0.00% 0/3 • First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.
Metabolism and nutrition disorders Dehydration	25.0% 1/4 • First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.	0.00% 0/3 • First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.	0.00% 0/3 • First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.	0.00% 0/3 • First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/4 • First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.	0.00% 0/3 • First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.	33.3% 1/3 • First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.	0.00% 0/3 • First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/4 • First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.	0.00% 0/3 • First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.	33.3% 1/3 • First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.	0.00% 0/3 • First dose date to last dose date (average: 14.5 weeks; maximum: 53 weeks) plus 30 days Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.

Other adverse events

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER