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NCT04747470

Study to Assess the Effects of GS-3583 in Participants With Advanced Solid Tumors

Terminated Phase 1 Results posted Last updated 3 September 2024
What this trial tests

Phase 1 trial testing GS-3583 in Advanced Solid Tumors in 13 participants. Terminated before completion.

Timeline
25 March 2021
Primary endpoint
7 November 2022
7 November 2022

Quick facts

Lead sponsorGilead Sciences
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment13
Start date25 March 2021
Primary completion7 November 2022
Estimated completion7 November 2022
Sites4 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Gilead Sciences — full company profile →

Who can join

18 and older, any sex, with Advanced Solid Tumors. 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.

Parts 1 and 2: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) Primary · Part 1: Day 1 through Day 28; Part 2: Day 1 through Day 21

DLT was defined as any toxicity (hematologic, non-hematologic, dosing/procedures-related toxicities, or grade 5 event (ie death)) occurring with GS-3583 monotherapy during the DLT assessment period (from Day 1 up to Day 28) considered at least possibly related to GS-3583 monotherapy.

GroupValue95% CI
Part 1: Cohort 2: GS-3583 2000 μg0
Part 1: Cohort 3: GS-3583 6000 μg0
Part 1: Cohort 4: GS-3583 12000 μg0
Part 1: Cohort 5: GS-3583 20000 μg0
Parts 1 and 2: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Primary · First dose date up to last dose date plus 90 days (Up to 4 months)

TEAEs were AEs with onset dates on or after the first dose and up to 90 days after the date of the last dose of study treatment or the day before initiation of subsequent therapy, whichever occurred first. TEAEs severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Fatal. Participants were counted at the highest AE grade experienced.

GroupValue95% CI
Part 1: Cohort 2: GS-3583 2000 μg100
Part 1: Cohort 3: GS-3583 6000 μg100
Part 1: Cohort 4: GS-3583 12000 μg100
Part 1: Cohort 5: GS-3583 20000 μg100
Parts 1 and 2: Percentage of Participants With Laboratory Abnormalities According to the NCI CTCAE Version 5.0 Primary · First dose date up to last dose date plus 90 days (Up to 4 months)

A treatment-emergent laboratory abnormality was defined as an increase of at least 1 toxicity grade from baseline at any time, up to 90 days after the last dose of study drug or the day before initiation of subsequent therapy, whichever occurred first. A treatment-emergent laboratory abnormality severity was graded according to the NCI CTCAE version 5.0. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Fatal. Participants were counted at the highest AE grade experienced.

GroupValue95% CI
Part 1: Cohort 2: GS-3583 2000 μg100
Part 1: Cohort 3: GS-3583 6000 μg100
Part 1: Cohort 4: GS-3583 12000 μg100
Part 1: Cohort 5: GS-3583 20000 μg100
Parts 1 and 2: Percentage of Participants With GS-3583 Anti-drug Antibodies (ADAs) at Any Visit Primary · Cycles 1and 3,pre-dose,End of Infusion (EOI);2,6 hours;Days 2,3,5,8,15 post Day 1EOI;Day 15:Cycle 1:predose and EOI;2 hours post EOI;Cycle 3:336 hours and Day 24 post EOI(Cycle length = 28 days in Part 1; 21 days for Part 2;infusion duration=60 minutes)

Participants were monitored for the development of ADAs throughout their treatment period with GS-3583 and at the end of study.

GroupValue95% CI
Part 1: Cohort 2: GS-3583 2000 μg33.3
Part 1: Cohort 3: GS-3583 6000 μg33.3
Part 1: Cohort 4: GS-3583 12000 μg0
Part 1: Cohort 5: GS-3583 20000 μg0
Part 1: Pharmacokinetic (PK) Parameter: AUCtau of GS-3583 Secondary · Cycles 1 and 3, pre-dose, EOI; 2, 6 hours; Days 2, 3, 5, 8, 15 post Day 1 EOI; Day 15:Cycle 1:predose and EOI; 2 hours post EOI;Cycle 3:336 hours and Day 24 post EOI (Cycle length for all cycles=28 days in Part 1; Infusion duration=60 minutes)

AUCtau is defined as the area under the concentration versus time curve over the dosing interval where tau = 15 days.

Cycle 1
GroupValue95% CI
Part 1: Cohort 2: GS-3583 2000 μg82100± 19900
Part 1: Cohort 3: GS-3583 6000 μg249000± 124000
Part 1: Cohort 4: GS-3583 12000 μg352000± 41300
Part 1: Cohort 5: GS-3583 20000 μg832000± 223000
Part 1: PK Parameter: Cmax of GS-3583 Secondary · Cycles 1 and 3,pre-dose,EOI;2, 6 hours;Days 2, 3, 5, 8, 15 post Day 1 EOI;Day 15:Cycle 1:predose and EOI;2 hours post EOI;Cycle 3:336 hours and Day 24 post EOI (Cycle length for all cycles=28 days in Part 1;Infusion duration=60 minutes)

Cmax is defined as the maximum observed plasma concentration.

Cycle 1
GroupValue95% CI
Part 1: Cohort 2: GS-3583 2000 μg643± 36.3
Part 1: Cohort 3: GS-3583 6000 μg1860± 562
Part 1: Cohort 4: GS-3583 12000 μg2520± 244
Part 1: Cohort 5: GS-3583 20000 μg5800± 1460
Part 1: PK Parameter: Tmax of GS-3583 Secondary · Cycles 1 and 3, pre-dose, EOI; 2, 6 hours; Days 2, 3, 5, 8, 15 post Day 1 EOI; Day 15:Cycle 1:predose and EOI; 2 hours post EOI; Cycle 3:336 hours and Day 24 post EOI (Cycle length for all cycles=28 days in Part 1; infusion duration=60 minutes)

Tmax is defined as the time to reach maximum observed plasma concentration (Tmax).

Cycle 1
GroupValue95% CI
Part 1: Cohort 2: GS-3583 2000 μg1.11.0 – 1.1
Part 1: Cohort 3: GS-3583 6000 μg2.01.1 – 5.6
Part 1: Cohort 4: GS-3583 12000 μg1.11.1 – 2.0
Part 1: Cohort 5: GS-3583 20000 μg1.71.2 – 2.1

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 14.8 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part 1: Cohort 1: GS-3583 675 μg
Serious: 0
Deaths: 0
Part 1: Cohort 2: GS-3583 2000 μg
Serious: 2/3 (67%)
Deaths: 3/3
Part 1: Cohort 3: GS-3583 6000 μg
Serious: 1/3 (33%)
Deaths: 2/3
Part 1: Cohort 4: GS-3583 12000 μg
Serious: 2/3 (67%)
Deaths: 2/3
Part 1: Cohort 5: GS-3583 20000 μg
Serious: 1/4 (25%)
Deaths: 2/4
Part 2: Safety Run-In Cohort A: GS-3583 + Combination Anticancer Therapy
Serious: 0
Deaths: 0
Part 2: Safety Run-In Cohort B: GS-3583 + Combination Anticancer Therapy
Serious: 0
Deaths: 0
Part 2: Randomized Expansion Cohort A: GS-3583 + Combination Anticancer Therapy
Serious: 0
Deaths: 0
Part 2: Randomized Expansion Cohort A: Combination Anticancer Therapy
Serious: 0
Deaths: 0
Part 2: Randomized Expansion Cohort B: GS-3583 + Combination Anticancer Therapy
Serious: 0
Deaths: 0
Part 2: Randomized Expansion Cohort B: Combination Anticancer Therapy
Serious: 0
Deaths: 0

Serious adverse events (7 terms)

ReactionSystemPart 1: Cohort 1: GS-3583 …Part 1: Cohort 2: GS-3583 …Part 1: Cohort 3: GS-3583 …Part 1: Cohort 4: GS-3583 …Part 1: Cohort 5: GS-3583 …Part 2: Safety Run-In Coho…Part 2: Safety Run-In Coho…Part 2: Randomized Expansi…Part 2: Randomized Expansi…Part 2: Randomized Expansi…Part 2: Randomized Expansi…
Abdominal painGastrointestinal disorders
Large intestinal obstructionGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
SepsisInfections and infestations
HyponatraemiaMetabolism and nutrition disorders
Second primary malignancyNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Cerebrovascular accidentNervous system disorders
Other adverse events (31 terms — click to expand)

ReactionSystemPart 1: Cohort 1: GS-3583 …Part 1: Cohort 2: GS-3583 …Part 1: Cohort 3: GS-3583 …Part 1: Cohort 4: GS-3583 …Part 1: Cohort 5: GS-3583 …Part 2: Safety Run-In Coho…Part 2: Safety Run-In Coho…Part 2: Randomized Expansi…Part 2: Randomized Expansi…Part 2: Randomized Expansi…Part 2: Randomized Expansi…
FatigueGeneral disorders
Tumour painNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
NauseaGastrointestinal disorders
Bone painMusculoskeletal and connective tissue disorders
ThrombocytopeniaBlood and lymphatic system disorders
Abdominal pain upperGastrointestinal disorders
AscitesGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
VomitingGastrointestinal disorders
Oedema peripheralGeneral disorders
PainGeneral disorders
HypertransaminasaemiaHepatobiliary disorders
BacteraemiaInfections and infestations
BronchitisInfections and infestations
Covid-19Infections and infestations
Oral candidiasisInfections and infestations
Blood alkaline phosphatase increasedInvestigations
Blood bilirubin increasedInvestigations
Weight decreasedInvestigations
DehydrationMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
DizzinessNervous system disorders
HeadacheNervous system disorders
DepressionPsychiatric disorders
Mental status changesPsychiatric disorders
CoughRespiratory, thoracic and mediastinal disorders
Night sweatsSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders

Most-reported serious reactions: Abdominal pain, Large intestinal obstruction, Small intestinal obstruction, Sepsis, Hyponatraemia, Second primary malignancy, Cerebrovascular accident.

Data from ClinicalTrials.gov NCT04747470 adverse events section.

Sponsor's own description

This study is planned to be conducted in 2 parts: Part 1: Dose Escalation and Part 2: Safety Run-In and Randomized Expansion. The primary objectives of Part 1 are 1) To characterize the safety and tolerability of GS-3583 as monotherapy in participants with advanced solid tumors. 2) To determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of GS-3583 as monotherapy in participants with advanced solid tumors. The primary objectives of Part 2 is to assess the safety and tolerability and to determine the RP2D of GS-3583 in combination with zimberelimab (ZIM) and platinum (cisplatin or carboplatin) + 5-fluorouracil (5-FU) chemotherapy in participants with head and neck squamous cell carcinoma (HNSCC) (Cohort A) or in combination with docetaxel in participants with non-small cell lung cancer (NSCLC) (Cohort B).

Publications & conference data

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

  1. Expanding cross-presenting dendritic cells enhances oncolytic virotherapy and is critical for long-term anti-tumor immunity.
    Svensson-Arvelund J, Cuadrado-Castano S, Pantsulaia G, Kim K, et al · · 2022 · cited 56× · PMID 36418317 · DOI 10.1038/s41467-022-34791-8
  2. Phase I Study of GS-3583, an FMS-like Tyrosine Kinase 3 Agonist Fc Fusion Protein, in Patients with Advanced Solid Tumors.
    Tolcher AW, Brody JD, Rajakumaraswamy N, Kuhne M, et al · · 2024 · cited 13× · PMID 38295150 · DOI 10.1158/1078-0432.ccr-23-2808

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing