Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of GS-4224 in Participants With Advanced Solid Tumors

Sponsor

Gilead Sciences (Industry)

Overall Status

Terminated

CT.gov ID

NCT04049617

Collaborator

(none)

Enrollment

Locations

Arms

19.1

Actual Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objectives of this study are to characterize the safety and tolerability of GS-4224 and to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of GS-4224 in participants with advanced solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Drug: GS-4224	Phase 1

Detailed Description

This was a planned Phase 1/2 study. However, Phase 2 was not conducted because the study was closed due to sponsor decision prior to opening the dose expansion cohort and hence, RP2D analysis was not performed.

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1b/2 Dose Escalation/Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of GS-4224 in Subjects With Advanced Solid Tumors

Actual Study Start Date :

Aug 26, 2019

Actual Primary Completion Date :

Mar 30, 2021

Actual Study Completion Date :

Mar 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: GS-4224 400 mg (Phase 1) Participants will receive GS-4224 400 mg once daily for 21 days of each cycle.	Drug: GS-4224 Tablets administered orally.
Experimental: Cohort 2: GS-4224 700 mg (Phase 1) Participants will receive GS-4224 700 mg once daily for 21 days of each cycle.	Drug: GS-4224 Tablets administered orally.
Experimental: Cohort 3: GS-4224 1000 mg (Phase 1) Participants will receive GS-4224 1000 mg once daily for 21 days of each cycle.	Drug: GS-4224 Tablets administered orally.
Experimental: Cohort 4: GS-4224 1500 mg (Phase 1) Participants will receive GS-4224 1500 mg once daily for 21 days of each cycle.	Drug: GS-4224 Tablets administered orally.
Experimental: Cohort 5: GS-4224 1000 mg (Phase 1) Participants are planned to receive GS-4224 1000 mg twice daily (BID) for 21 days of each cycle.	Drug: GS-4224 Tablets administered orally.
Experimental: Cohort 1 Substudy: GS-4224 400 mg (Phase 1) Participants will receive GS-4224 400 mg once daily for 21 days of each cycle.	Drug: GS-4224 Tablets administered orally.
Experimental: Cohort 2 Substudy: GS-4224 700 mg (Phase 1) Participants are planned to receive GS-4224 700 mg once daily for 21 days of each cycle.	Drug: GS-4224 Tablets administered orally.
Experimental: Cohort 3 Substudy: GS-4224 1000 mg (Phase 1) Participants will receive GS-4224 1000 mg once daily for 21 days of each cycle.	Drug: GS-4224 Tablets administered orally.
Experimental: Dose Expansion (Phase 2) Dose expansion is planned to begin when the recommended Phase 2 dose (RP2D) will be determined.	Drug: GS-4224 Tablets administered orally.

Outcome Measures

Primary Outcome Measures

Number of Participants Experiencing Dose Limiting Toxicities (DLTs) During the Dose Escalation Phase [Day 1 through Day 21]
A DLT was any toxicity defined as follows excluding toxicities clearly related to disease progression or disease-related processes occurring during the DLT assessment window (Day 1 through Day 21): Grade ≥ 4 neutropenia Grade ≥ 3 neutropenia with fever Grade ≥ 3 thrombocytopenia Grade ≥ 2 bleeding Grade ≥ 3 anemia Grade ≥ 3 or higher non-hematologic toxicity (excluding Grade 3 nausea or emesis or Grade 3 diarrhea) Grade ≥ 2 non-hematologic treatment-emergent adverse event that in the opinion of the investigator is of potential clinical significance Treatment interruption of ≥ 7 days due to unresolved toxicity Any toxicity event that precludes further administration of GS-4224 Any Grade 3 or Grade 4 elevation in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) associated with a Grade 2 elevation in bilirubin lasting ≥ 7 days An immune-related adverse event (irAE) for which immunotherapy should be permanently discontinued

Secondary Outcome Measures

Pharmacokinetic (PK) Parameter: AUCtau of GS-4224 During the Dose Escalation Phase [Intensive PK: Predose, 0-24 hours (h) post dose (400-1500 mg cohorts) on Cycle (C) 1 Day (D) 1 & D15]
AUCtau was defined as area under the concentration-time curve from time zero to the end of the dosing interval.
PK Parameter: Cmax of GS-4224 During the Dose Escalation Phase [Intensive PK: Predose, 0-24 hours (h) post dose (400-1500 mg cohorts) on C1D1 & D15]
Cmax was defined as the maximum observed drug concentration.
PK Parameter: Ctrough of GS-4224 During the Dose Escalation Phase [Intensive PK: Predose, 0-24 hours (h) post dose (400-1500 mg cohorts) on C1D1 & D15]
Ctrough is defined as the observed concentration at the end of the dosing interval.
PK Parameter: Tmax of GS-4224 During the Dose Escalation Phase [Intensive PK: Predose, 0-24 hours (h) post dose (400-1500 mg cohorts) on C1D1 & D15]
Tmax is defined as the time to maximum observed concentration.
Percentage of Participants Experiencing ≥ Grade 3 Treatment-Emergent Adverse Events During the Dose Expansion Phase [First dose date through end of treatment plus 30 days, approximately 5 years]
Percentage of Participants Experiencing ≥ Grade 3 Treatment-Emergent Laboratory Abnormalities During the Dose Expansion Phase [First dose date through end of treatment plus 30 days, approximately 5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Dose Escalation Cohorts: Histologically or cytologically confirmed advanced malignant solid tumor that is refractory to or intolerant of all standard therapy or for which no standard therapy is available.
Dose Expansion and 1000 mg twice a day (BID) Dose Escalation Cohorts: Individuals must have available sufficient and adequate formalin fixed tumor sample preferably from a biopsy of a tumor lesion obtained either at the time of or after the diagnosis of advanced disease has been made and from a site not previously irradiated. Alternatively, individuals must agree to have a biopsy taken prior to entering the study to provide adequate tissue. For the 1000 mg BID dose escalation cohort, individuals with melanoma, Merkel cell, microsatellite instability-high (MSI-H) cancers, and classical Hodgkin lymphoma (cHL) are not required to have archival or fresh biopsy tissue.
Dose Escalation Biopsy Substudy and 1000 mg BID Dose Escalation Cohorts: Documented ligand 1 of programmed cell death protein 1 (PD-L1) expression in the tumor (tumor proportion score (TPS) ≥ 10% or combined positive score (CPS) ≥ 10). In the 1000 mg BID Cohort, PD-L1 expression will not be required for Merkel cell, melanoma, MSI-H cancers, and cHL.
Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
Adequate organ function.

Key Exclusion Criteria:

History or evidence of clinically significant disorder, condition, or disease that, in the opinion of the Investigator or Medical Monitor would pose a risk to individual safety or interfere with the study evaluations, procedures, or completion.
Dose Escalation Cohorts: History of ≥ Grade 3 Adverse Events (AEs) during prior treatment with an immune checkpoint inhibitor, or history of discontinuation of treatment with an immune checkpoint inhibitor due to AEs.
Dose Escalation 1000 mg BID and Dose Expansion Cohort: Prior treatment with an immune checkpoint inhibitor (anti-PD-1, anti-PD-L1, or anti- ligand 2 of programmed cell death protein 1 (PD-L2) antibodies).
History of autoimmune disease (for example, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	California Care Associates for Research and Excellence Inc	Encinitas	California	United States	92024
2	NEXT Oncology	San Antonio	Texas	United States	78229
3	Northwest Medical Specialties, PLLC	Tacoma	Washington	United States	98405
4	Auckland City Hospital	Auckland		New Zealand	1023
5	Christchurch Clinical Studies Trust, LLC	Christchurch		New Zealand	8011
6	Auckland Clinical Studies Ltd	Grafton, Auckland		New Zealand	1010

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

Gilead Sciences

ClinicalTrials.gov Identifier:

NCT04049617

Other Study ID Numbers:

GS-US-494-5484
2019-004605-27

First Posted:

Aug 8, 2019

Last Update Posted:

Aug 10, 2022

Last Verified:

Mar 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Neoplasms

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in New Zealand and the United States. The first participant was screened on 26 August 2019. The last study visit occurred on 30 March 2021.
Pre-assignment Detail	29 participants were screened. The participants took part in the Phase 1 (Dose Escalation) of the study only. No participants were enrolled in the Phase 1 Cohort 5 and Cohort 2 substudy and the study was terminated due to sponsor decision before the planned Dose Expansion Phase 2 started.

Arm/Group Title	Cohort 1: GS-4224 400 mg (Phase 1)	Cohort 2: GS-4224 700 mg (Phase 1)	Cohort 3: GS-4224 1000 mg (Phase 1)	Cohort 4: GS-4224 1500 mg (Phase 1)	Cohort 1 Substudy: GS-4224 400 mg (Phase 1)	Cohort 3 Substudy: GS-4224 1000 mg (Phase 1)
Arm/Group Description	Participants received GS-4224 400 mg once daily for 21 days of each cycle (observed maximum duration was approximately 21 weeks).	Participants received GS-4224 700 mg once daily for 21 days of each cycle (observed maximum duration was approximately 10 weeks).	Participants received GS-4224 1000 mg once daily for 21 days of each cycle (observed maximum duration was approximately 39 weeks).	Participants received GS-4224 1500 mg once daily for 21 days of each cycle (observed maximum duration was approximately 19 weeks).	Participants received GS-4224 400 mg once daily for 21 days of each cycle (observed maximum duration was approximately 39 weeks).	Participants received GS-4224 1000 mg once daily for 21 days of each cycle (observed maximum duration was approximately 10 weeks).
Period Title: Overall Study
STARTED	3	3	6	3	2	1
COMPLETED	3	3	5	1	2	0
NOT COMPLETED	0	0	1	2	0	1

Baseline Characteristics

Arm/Group Title	Cohort 1: GS-4224 400 mg (Phase 1)	Cohort 2: GS-4224 700 mg (Phase 1)	Cohort 3: GS-4224 1000 mg (Phase 1)	Cohort 4: GS-4224 1500 mg (Phase 1)	Cohort 1 Substudy: GS-4224 400 mg (Phase 1)	Cohort 3 Substudy: GS-4224 1000 mg (Phase 1)	Total
Arm/Group Description	Participants received GS-4224 400 mg once daily for 21 days of each cycle (observed maximum duration was approximately 21 weeks).	Participants received GS-4224 700 mg once daily for 21 days of each cycle (observed maximum duration was approximately 10 weeks).	Participants received GS-4224 1000 mg once daily for 21 days of each cycle (observed maximum duration was approximately 39 weeks).	Participants received GS-4224 1500 mg once daily for 21 days of each cycle (observed maximum duration was approximately 19 weeks).	Participants received GS-4224 400 mg once daily for 21 days of each cycle (observed maximum duration was approximately 39 weeks).	Participants received GS-4224 1000 mg once daily for 21 days of each cycle (observed maximum duration was approximately 10 weeks).	Total of all reporting groups
Overall Participants	3	3	6	3	2	1	18
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.3 (28.29)	65.3 (15.53)	61.2 (5.67)	70.0 (11.53)	64.0 (12.73)	42.0 (NA)	61.6 (14.23)
Sex: Female, Male (Count of Participants)
Female	1 33.3%	0 0%	2 33.3%	0 0%	0 0%	0 0%	3 16.7%
Male	2 66.7%	3 100%	4 66.7%	3 100%	2 100%	1 100%	15 83.3%
Race/Ethnicity, Customized (Count of Participants)
Race	NA NaN	NA NaN	NA NaN	NA NaN	NA NaN	NA NaN	NA NaN
Race/Ethnicity, Customized (Count of Participants)
Ethnicity	NA NaN	NA NaN	NA NaN	NA NaN	NA NaN	NA NaN	NA NaN
Region of Enrollment (participants) [Number]
New Zealand	1 33.3%	2 66.7%	5 83.3%	2 66.7%	2 100%	0 0%	12 66.7%
United States	2 66.7%	1 33.3%	1 16.7%	1 33.3%	0 0%	1 100%	6 33.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Experiencing Dose Limiting Toxicities (DLTs) During the Dose Escalation Phase
Description	A DLT was any toxicity defined as follows excluding toxicities clearly related to disease progression or disease-related processes occurring during the DLT assessment window (Day 1 through Day 21): Grade ≥ 4 neutropenia Grade ≥ 3 neutropenia with fever Grade ≥ 3 thrombocytopenia Grade ≥ 2 bleeding Grade ≥ 3 anemia Grade ≥ 3 or higher non-hematologic toxicity (excluding Grade 3 nausea or emesis or Grade 3 diarrhea) Grade ≥ 2 non-hematologic treatment-emergent adverse event that in the opinion of the investigator is of potential clinical significance Treatment interruption of ≥ 7 days due to unresolved toxicity Any toxicity event that precludes further administration of GS-4224 Any Grade 3 or Grade 4 elevation in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) associated with a Grade 2 elevation in bilirubin lasting ≥ 7 days An immune-related adverse event (irAE) for which immunotherapy should be permanently discontinued
Time Frame	Day 1 through Day 21

Outcome Measure Data

Analysis Population Description
Safety Analysis Set included data from all participants who received at least 1 dose of study treatment, with treatment assignments designated according to the actual treatment received.

Arm/Group Title	Cohort 1: GS-4224 400 mg (Phase 1)	Cohort 2: GS-4224 700 mg (Phase 1)	Cohort 3: GS-4224 1000 mg (Phase 1)	Cohort 4: GS-4224 1500 mg (Phase 1)	Cohort 1 Substudy: GS-4224 400 mg (Phase 1)	Cohort 3 Substudy: GS-4224 1000 mg (Phase 1)
Arm/Group Description	Participants received GS-4224 400 mg once daily for 21 days of each cycle (observed maximum duration was approximately 21 weeks).	Participants received GS-4224 700 mg once daily for 21 days of each cycle (observed maximum duration was approximately 10 weeks).	Participants received GS-4224 1000 mg once daily for 21 days of each cycle (observed maximum duration was approximately 39 weeks).	Participants received GS-4224 1500 mg once daily for 21 days of each cycle (observed maximum duration was approximately 19 weeks).	Participants received GS-4224 400 mg once daily for 21 days of each cycle (observed maximum duration was approximately 39 weeks).	Participants received GS-4224 1000 mg once daily for 21 days of each cycle (observed maximum duration was approximately 10 weeks).
Measure Participants	3	3	6	3	2	1
Count of Participants [Participants]	0 0%	0 0%	0 0%	1 33.3%	0 0%	0 0%

2. Secondary Outcome

Title	Pharmacokinetic (PK) Parameter: AUCtau of GS-4224 During the Dose Escalation Phase
Description	AUCtau was defined as area under the concentration-time curve from time zero to the end of the dosing interval.
Time Frame	Intensive PK: Predose, 0-24 hours (h) post dose (400-1500 mg cohorts) on Cycle (C) 1 Day (D) 1 & D15

Outcome Measure Data

Analysis Population Description
PK Analysis Set included participants in the Safety Analysis Set who had received the study drug and have at least 1 sample with detectable drug concentration. Data for Cohort 1 included participants from Cohort 1 and Substudy Cohort 1. PK data were not collected for Cohort 3 Substudy group due to discontinuation of the development program.

Arm/Group Title	Cohort 1: GS-4224 400 mg (Phase 1)	Cohort 2: GS-4224 700 mg (Phase 1)	Cohort 3: GS-4224 1000 mg (Phase 1)	Cohort 4: GS-4224 1500 mg (Phase 1)
Arm/Group Description	Participants received GS-4224 400 mg once daily for 21 days of each cycle (observed maximum duration was approximately 21 weeks).	Participants received GS-4224 700 mg once daily for 21 days of each cycle (observed maximum duration was approximately 10 weeks).	Participants received GS-4224 1000 mg once daily for 21 days of each cycle (observed maximum duration was approximately 39 weeks).	Participants received GS-4224 1500 mg once daily for 21 days of each cycle (observed maximum duration was approximately 19 weeks).
Measure Participants	5	3	6	3
C1D1	6543.1 (1783.07)	8703.8 (3717.93)	12241.8 (2793.17)	19132.6 (596.64)
C1D15	9269.8 (2693.53)	13508.4 (3126.80)	19380.8 (5261.89)	27664.5 (7758.37)

3. Secondary Outcome

Title	PK Parameter: Cmax of GS-4224 During the Dose Escalation Phase
Description	Cmax was defined as the maximum observed drug concentration.
Time Frame	Intensive PK: Predose, 0-24 hours (h) post dose (400-1500 mg cohorts) on C1D1 & D15

Outcome Measure Data

Analysis Population Description
Participants in PK Analysis Set were analyzed. Data for Cohort 1 included participants from Cohort 1 and Substudy Cohort 1. PK data were not collected for Cohort 3 Substudy group due to discontinuation of the development program.

Arm/Group Title	Cohort 1: GS-4224 400 mg (Phase 1)	Cohort 2: GS-4224 700 mg (Phase 1)	Cohort 3: GS-4224 1000 mg (Phase 1)	Cohort 4: GS-4224 1500 mg (Phase 1)
Arm/Group Description	Participants received GS-4224 400 mg once daily for 21 days of each cycle (observed maximum duration was approximately 21 weeks).	Participants received GS-4224 700 mg once daily for 21 days of each cycle (observed maximum duration was approximately 10 weeks).	Participants received GS-4224 1000 mg once daily for 21 days of each cycle (observed maximum duration was approximately 39 weeks).	Participants received GS-4224 1500 mg once daily for 21 days of each cycle (observed maximum duration was approximately 19 weeks).
Measure Participants	5	3	6	3
C1D1	1090.4 (355.12)	1468.7 (497.74)	1918.3 (377.59)	2116.7 (55.08)
C1D15	1193.8 (605.87)	1580.0 (245.76)	2051.7 (686.89)	2480.0 (278.75)

4. Secondary Outcome

Title	PK Parameter: Ctrough of GS-4224 During the Dose Escalation Phase
Description	Ctrough is defined as the observed concentration at the end of the dosing interval.
Time Frame	Intensive PK: Predose, 0-24 hours (h) post dose (400-1500 mg cohorts) on C1D1 & D15

Outcome Measure Data

Analysis Population Description
Participants in the PK Analysis Set were analyzed. Data for Cohort 1 included participants from Cohort 1 and Substudy Cohort 1. PK data were not collected for Cohort 3 Substudy group due to discontinuation of the development program.

Arm/Group Title	Cohort 1: GS-4224 400 mg (Phase 1)	Cohort 2: GS-4224 700 mg (Phase 1)	Cohort 3: GS-4224 1000 mg (Phase 1)	Cohort 4: GS-4224 1500 mg (Phase 1)
Arm/Group Description	Participants received GS-4224 400 mg once daily for 21 days of each cycle (observed maximum duration was approximately 21 weeks).	Participants received GS-4224 700 mg once daily for 21 days of each cycle (observed maximum duration was approximately 10 weeks).	Participants received GS-4224 1000 mg once daily for 21 days of each cycle (observed maximum duration was approximately 39 weeks).	Participants received GS-4224 1500 mg once daily for 21 days of each cycle (observed maximum duration was approximately 19 weeks).
Measure Participants	5	3	6	3
C1D1	40.3 (9.80)	56.2 (18.05)	111.9 (43.92)	180.3 (21.50)
C1D15	109.8 (35.61)	198.7 (57.98)	318.5 (88.44)	472.7 (112.88)

5. Secondary Outcome

Title	PK Parameter: Tmax of GS-4224 During the Dose Escalation Phase
Description	Tmax is defined as the time to maximum observed concentration.
Time Frame	Intensive PK: Predose, 0-24 hours (h) post dose (400-1500 mg cohorts) on C1D1 & D15

Outcome Measure Data

Analysis Population Description
Participants in PK Analysis Set were analyzed. Data for Cohort 1 included participants from Cohort 1 and Substudy Cohort 1. PK data were not collected for Cohort 3 Substudy group due to discontinuation of the development program.

Arm/Group Title	Cohort 1: GS-4224 400 mg (Phase 1)	Cohort 2: GS-4224 700 mg (Phase 1)	Cohort 3: GS-4224 1000 mg (Phase 1)	Cohort 4: GS-4224 1500 mg (Phase 1)
Arm/Group Description	Participants received GS-4224 400 mg once daily for 21 days of each cycle (observed maximum duration was approximately 21 weeks).	Participants received GS-4224 700 mg once daily for 21 days of each cycle (observed maximum duration was approximately 10 weeks).	Participants received GS-4224 1000 mg once daily for 21 days of each cycle (observed maximum duration was approximately 39 weeks).	Participants received GS-4224 1500 mg once daily for 21 days of each cycle (observed maximum duration was approximately 19 weeks).
Measure Participants	5	3	6	3
C1D1	1.00	1.53	1.52	2.50
C1D15	1.50	1.50	1.51	4.00

6. Secondary Outcome

Title	Percentage of Participants Experiencing ≥ Grade 3 Treatment-Emergent Adverse Events During the Dose Expansion Phase
Description
Time Frame	First dose date through end of treatment plus 30 days, approximately 5 years

Outcome Measure Data

Analysis Population Description
The study was closed due to sponsor decision prior to opening the dose expansion phase. Hence, no participants were analyzed in this phase.

Arm/Group Title	Dose Expansion (Phase 2)
Arm/Group Description	Dose expansion was planned to begin when the recommended Phase 2 dose (RP2D) was determined. The study was closed due to sponsor decision prior to opening the dose expansion cohort and hence RP2D analysis was not performed.
Measure Participants	0

7. Secondary Outcome

Title	Percentage of Participants Experiencing ≥ Grade 3 Treatment-Emergent Laboratory Abnormalities During the Dose Expansion Phase
Description
Time Frame	First dose date through end of treatment plus 30 days, approximately 5 years

Outcome Measure Data

Analysis Population Description
The study was closed due to sponsor decision prior to opening the dose expansion phase. Hence, no participants were analyzed in this phase.

Arm/Group Title	Dose Expansion (Phase 2)
Arm/Group Description	Dose expansion was planned to begin when the recommended Phase 2 dose (RP2D) was determined. The study was closed due to sponsor decision prior to opening the dose expansion cohort and hence RP2D analysis was not performed.
Measure Participants	0

Adverse Events

	Cohort 1: GS-4224 400 mg (Phase 1)		Cohort 2: GS-4224 700 mg (Phase 1)		Cohort 3: GS-4224 1000 mg (Phase 1)		Cohort 4: GS-4224 1500 mg (Phase 1)		Cohort 1 Substudy: GS-4224 400 mg (Phase 1)		Cohort 3 Substudy: GS-4224 1000 mg (Phase 1)
Time Frame	All-Cause Mortality: Enrollment up to 46.1 weeks Adverse Events: First dose date up to last dose (maximum: 39.1 weeks) plus 30 days
Adverse Event Reporting Description	All-Cause Mortality: All Enrolled Analysis Set included all participants who received a study identification number in the study after screening. Adverse Events: Safety Analysis Set included data from all participants who received at least 1 dose of study treatment, with treatment assignments designated according to the actual treatment received.

Arm/Group Title	Cohort 1: GS-4224 400 mg (Phase 1)		Cohort 2: GS-4224 700 mg (Phase 1)		Cohort 3: GS-4224 1000 mg (Phase 1)		Cohort 4: GS-4224 1500 mg (Phase 1)		Cohort 1 Substudy: GS-4224 400 mg (Phase 1)		Cohort 3 Substudy: GS-4224 1000 mg (Phase 1)
Arm/Group Description	Participants received GS-4224 400 mg once daily for 21 days of each cycle (observed maximum duration was approximately 21 weeks).		Participants received GS-4224 700 mg once daily for 21 days of each cycle (observed maximum duration was approximately 10 weeks).		Participants received GS-4224 1000 mg once daily for 21 days of each cycle (observed maximum duration was approximately 39 weeks).		Participants received GS-4224 1500 mg once daily for 21 days of each cycle (observed maximum duration was approximately 19 weeks).		Participants received GS-4224 400 mg once daily for 21 days of each cycle (observed maximum duration was approximately 39 weeks).		Participants received GS-4224 1000 mg once daily for 21 days of each cycle (observed maximum duration was approximately 10 weeks).
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/2 (0%)		1/1 (100%)
Serious Adverse Events
	Cohort 1: GS-4224 400 mg (Phase 1)		Cohort 2: GS-4224 700 mg (Phase 1)		Cohort 3: GS-4224 1000 mg (Phase 1)		Cohort 4: GS-4224 1500 mg (Phase 1)		Cohort 1 Substudy: GS-4224 400 mg (Phase 1)		Cohort 3 Substudy: GS-4224 1000 mg (Phase 1)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		1/3 (33.3%)		1/6 (16.7%)		1/3 (33.3%)		0/2 (0%)		1/1 (100%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/2 (0%)		0/1 (0%)
Rectal perforation	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/2 (0%)		1/1 (100%)
Small intestinal obstruction	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
General disorders
Pyrexia	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Infections and infestations
Norovirus infection	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Sepsis	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/2 (0%)		1/1 (100%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1: GS-4224 400 mg (Phase 1)		Cohort 2: GS-4224 700 mg (Phase 1)		Cohort 3: GS-4224 1000 mg (Phase 1)		Cohort 4: GS-4224 1500 mg (Phase 1)		Cohort 1 Substudy: GS-4224 400 mg (Phase 1)		Cohort 3 Substudy: GS-4224 1000 mg (Phase 1)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		6/6 (100%)		3/3 (100%)		2/2 (100%)		0/1 (0%)
Blood and lymphatic system disorders
Anaemia	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		1/3 (33.3%)		0/2 (0%)		0/1 (0%)
Gastrointestinal disorders
Abdominal distension	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Abdominal pain	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		1/3 (33.3%)		0/2 (0%)		0/1 (0%)
Constipation	0/3 (0%)		1/3 (33.3%)		2/6 (33.3%)		1/3 (33.3%)		0/2 (0%)		0/1 (0%)
Diarrhoea	1/3 (33.3%)		1/3 (33.3%)		4/6 (66.7%)		2/3 (66.7%)		1/2 (50%)		0/1 (0%)
Dyspepsia	1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Gastritis	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		1/3 (33.3%)		0/2 (0%)		0/1 (0%)
Gastrooesophageal reflux disease	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Ileus	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Intestinal obstruction	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Nausea	3/3 (100%)		2/3 (66.7%)		4/6 (66.7%)		2/3 (66.7%)		1/2 (50%)		0/1 (0%)
Vomiting	1/3 (33.3%)		1/3 (33.3%)		1/6 (16.7%)		2/3 (66.7%)		0/2 (0%)		0/1 (0%)
General disorders
Chest pain	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/2 (50%)		0/1 (0%)
Chills	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Fatigue	1/3 (33.3%)		1/3 (33.3%)		1/6 (16.7%)		1/3 (33.3%)		1/2 (50%)		0/1 (0%)
Oedema peripheral	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/2 (0%)		0/1 (0%)
Hepatobiliary disorders
Gallbladder obstruction	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Infections and infestations
Lower respiratory tract infection	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Postoperative wound infection	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Respiratory tract infection	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/2 (0%)		0/1 (0%)
Injury, poisoning and procedural complications
Foot fracture	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/2 (0%)		0/1 (0%)
Skin abrasion	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/2 (0%)		0/1 (0%)
Investigations
Weight decreased	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/2 (0%)		0/1 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		1/3 (33.3%)		0/2 (0%)		0/1 (0%)
Dehydration	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		1/3 (33.3%)		0/2 (0%)		0/1 (0%)
Hypercalcaemia	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Hypokalaemia	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		1/3 (33.3%)		0/2 (0%)		0/1 (0%)
Hyponatraemia	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Hypophosphataemia	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/2 (0%)		0/1 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Back pain	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/2 (50%)		0/1 (0%)
Muscle spasms	1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Pain in extremity	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Nervous system disorders
Ageusia	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/2 (0%)		0/1 (0%)
Dizziness	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Migraine	1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Presyncope	0/3 (0%)		0/3 (0%)		2/6 (33.3%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Syncope	1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Psychiatric disorders
Depression	1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Insomnia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/2 (50%)		0/1 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/3 (0%)		0/3 (0%)		2/6 (33.3%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Dyspnoea	1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Nasal congestion	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/2 (0%)		0/1 (0%)
Pulmonary embolism	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Skin and subcutaneous tissue disorders
Intertrigo	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/2 (0%)		0/1 (0%)
Night sweats	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Psoriasis	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/2 (0%)		0/1 (0%)
Rash	2/3 (66.7%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/2 (0%)		0/1 (0%)
Vascular disorders
Deep vein thrombosis	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Thrombophlebitis superficial	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/2 (0%)		0/1 (0%)

Limitations/Caveats

Due to early termination, the study did not proceed to dose expansion phase.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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

Results Point of Contact

Name/Title	Gilead Clinical Study Information Center
Organization	Gilead Sciences
Phone	1-833-445-3230 (GILEAD-0)
Email	GileadClinicalTrials@gilead.com

Responsible Party:

Gilead Sciences

ClinicalTrials.gov Identifier:

NCT04049617

Other Study ID Numbers:

GS-US-494-5484
2019-004605-27

First Posted:

Aug 8, 2019

Last Update Posted:

Aug 10, 2022

Last Verified:

Mar 1, 2022

Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of GS-4224 in Participants With Advanced Solid Tumors

Study Details

Study Description

Brief Summary

Detailed Description

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Key Inclusion Criteria:

Key Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

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Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

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Certain Agreements

Results Point of Contact