Advanced Solid TumorsPhase 1NCT04747470
Study to Assess the Effects of GS-3583 in Participants With Advanced Solid Tumors
A Phase 1 study testing GS-3583, Zimberelimab and Cisplatin in people with Advanced Solid Tumors, run by Gilead Sciences at 4 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors
- What is being tested?
- GS-3583, Zimberelimab and Cisplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 4 sitesUnited States
- Study dates
- 25 Mar 2021to 7 Nov 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed locally advanced or metastatic malignant solid tumor that is refractory to or intolerant of standard therapy or for which no standard therapy is available
- Have measurable disease on imaging based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
- Eastern Cooperative oncology Group (ECOG) performance status of ≤ 2
- Life expectancy of ≥ 3 months, in the opinion of the investigator
- Adequate organ function as assessed by hematological, renal, and hepatic parameters, and no clinically significant coagulopathy
Who cannot join
- Received prior systemic cytotoxic chemotherapy, biological therapy, radiotherapy, or major surgery within 3 weeks of Cycle 1 Day 1; a 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease with sponsor approval
- Known severe hypersensitivity reactions (NCI CTCAE Grade ≥ 3) to fully human monoclonal antibodies or fusion proteins, GS-3583 formulation excipients, or severe reaction to immuno-oncology agents, such as colitis or pneumonitis requiring treatment with corticosteroids, any history of anaphylaxis, or uncontrolled asthma
- Concurrent active malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix, or superficial bladder cancer who has undergone potentially curative therapy with no evidence of disease. Individuals with other previous malignancies are eligible if disease free for > 2 years.
- Previous history of hematological malignancy, monoclonal gammopathy of unknown significance (MGUS) or other preleukemic states (Presence of clonal hematopoiesis of indeterminate potential (CHIP)/age related clonal hematopoiesis (ARCH) is acceptable)
- Known CNS metastasis(es), unless metastases are treated and stable and the individual does not require systemic corticosteroids for management of CNS symptoms at least 1 week prior to study treatment. Individuals with history of carcinomatous meningitis are excluded regardless of clinical stability.
- Active or history of autoimmune disease that has required systemic treatment within 2 years of the start of study treatment (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs)
- Note: Individuals with diabetes type 1, vitiligo, psoriasis, hypothyroid disease, or hyperthyroid disease, not requiring immunosuppressive treatment are eligible.
- Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
START Midwest
Grand Rapids, Michigan, 49546
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Oregon Health & Science University
Portland, Oregon, 97239
NEXT oncology
San Antonio, Texas, 78229
About this study
Official title: A Phase 1b Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of GS-3583, a FLT3 Agonist Fc Fusion Protein, in Subjects With Advanced Solid Tumors
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).
- Conditions
- Advanced Solid Tumors
- Being tested
- GS-3583, Zimberelimab, Cisplatin, Carboplatin, 5-Fluorouracil
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GS-3583Drug
Administered as an intravenous (IV) infusion
ZimberelimabDrug
Administered as an IV infusion
CisplatinDrug
Administered as an IV infusion
CarboplatinDrug
Administered as an IV infusion
5-FluorouracilDrug
Administered as an IV infusion
DocetaxelDrug
Administered as an IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Cohort 1: GS-3583 675 μg | Experimental | Participants with advanced solid tumors will receive GS-3583 675 μg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle for up to 13 cycles (up to 52 weeks) or until the participant met study treatment discontinuation criteria. Receives: Drug: GS-3583 |
| Part 1: Cohort 2: GS-3583 2000 μg | Experimental | Participants with advanced solid tumors will receive GS-3583 2000 μg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle for up to 13 cycles (up to 52 weeks) or until the participant met study treatment discontinuation criteria. Receives: Drug: GS-3583 |
| Part 1: Cohort 3: GS-3583 6000 μg | Experimental | Participants with advanced solid tumors will receive GS-3583 6000 μg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle for up to 13 cycles (up to 52 weeks) or until the participant met study treatment discontinuation criteria. Receives: Drug: GS-3583 |
| Part 1: Cohort 4: GS-3583 12000 μg | Experimental | Participants with advanced solid tumors will receive GS-3583 12000 μg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle for up to 13 cycles (up to 52 weeks) or until the participant met study treatment discontinuation criteria. Receives: Drug: GS-3583 |
| Part 1: Cohort 5: GS-3583 20000 μg | Experimental | Participants with advanced solid tumors will receive GS-3583 20000 μg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle for up to 13 cycles (up to 52 weeks) or until the participant met study treatment discontinuation criteria. Receives: Drug: GS-3583 |
| Part 2: Safety Run-In Cohort A: GS-3583 + Combination Anticancer Therapy | Experimental | Participants with head and neck squamous cell carcinoma (HNSCC) will receive GS-3583 at a dose determined in Part 1 on Day 1 of every 21-day cycles for up to 8 cycles + ZIM 360 mg, on Day 1 of each 21-day cycle up to 105 weeks + cisplatin 100 mg/m^2 of BSA on Day 1 of each 21-day cycle up to 6 cycles + carboplatin area under the curve 5 mg/mL/min on Day 1 of each 28- day cycle up to 6 cycles + 5-5-flourouracil (5-FU) 1000 mg/m^2 of BSA/day on Days 1 to 4 of 21-day cycle up to 6 cycles. Receives: Drug: GS-3583; Drug: Zimberelimab; Drug: Cisplatin; Drug: Carboplatin; Drug: 5-Fluorouracil |
| Part 2: Safety Run-In Cohort B: GS-3583 + Combination Anticancer Therapy | Experimental | Participants with non-small cell lung cancer (NSCLC) will receive GS-3583 at a dose determined in Part 1 on Day 1 of every 21-day cycles for up to 8 cycles + docetaxel 75 mg/m^2 on Day 1 of each 21-day cycle until 1 or more criteria for discontinuation are met. Receives: Drug: GS-3583; Drug: Docetaxel |
| Part 2: Randomized Expansion Cohort A: GS-3583 + Combination Anticancer Therapy | Experimental | Participants with HNSCC will receive GS-3583 at a dose determined in Part 1 on Day 1 of every 21-day cycles for up to 8 cycles + ZIM 360 mg, on Day 1 of each 21-day cycle up to 105 weeks + cisplatin 100 mg/m^2 of BSA on Day 1 of each 21-day cycle up to 6 cycles + carboplatin area under the curve 5 mg/mL/min on Day 1 of each 21-day cycle up to 6 cycles + 5-FU 1000 mg/m^2 of BSA/day on Days 1 to 4 of 21-day cycle up to 6 cycles. Receives: Drug: GS-3583; Drug: Zimberelimab; Drug: Cisplatin; Drug: Carboplatin; Drug: 5-Fluorouracil |
| Part 2: Randomized Expansion Cohort A: Combination Anticancer Therapy | Experimental | Participants with HNSCC will receive ZIM 360 mg, on Day 1 of each 21-day cycle up to 105 weeks + cisplatin 100 mg/m^2 of BSA on Day 1 of each 21-day cycle up to 6 cycles + carboplatin area under th e curve 5 mg/mL/min on Day 1 of each 21-day cycle up to 6 cycles + 5-FU 1000 mg/m^2 of BSA/day on Days 1 to 4 of 21-day cycle up to 6 cycles. Receives: Drug: Zimberelimab; Drug: Cisplatin; Drug: Carboplatin; Drug: 5-Fluorouracil |
| Part 2: Randomized Expansion Cohort B: GS-3583 + Combination Anticancer Therapy | Experimental | Participants with NSCLC will receive GS-3583 at a dose determined in Part 1 on Day 1 of every 21-day cycles for up to 8 cycles + docetaxel 75 mg/m^2 on Day 1 of each 21-day cycle until 1 or more criteria for discontinuation are met. Receives: Drug: GS-3583; Drug: Docetaxel |
| Part 2: Randomized Expansion Cohort B: Combination Anticancer Therapy | Experimental | Participants with NSCLC will receive docetaxel 75 mg/m^2 on Day 1 of each 21-day cycle until 1 or more criteria for discontinuation are met. Receives: Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Parts 1 and 2: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
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.
Measured: Part 1: Day 1 through Day 28; Part 2: Day 1 through Day 21
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
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.
Measured: First dose date up to last dose date plus 90 days (Up to 4 months)
Parts 1 and 2: Percentage of Participants With Laboratory Abnormalities According to the NCI CTCAE Version 5.0
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.
Measured: First dose date up to last dose date plus 90 days (Up to 4 months)
Parts 1 and 2: Percentage of Participants With GS-3583 Anti-drug Antibodies (ADAs) at Any Visit
Participants were monitored for the development of ADAs throughout their treatment period with GS-3583 and at the end of study.
Measured: 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)
Secondary outcomes (11)
Part 1: Pharmacokinetic (PK) Parameter: AUCtau of GS-3583
AUCtau is defined as the area under the concentration versus time curve over the dosing interval where tau = 15 days.
Measured: 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)
Part 1: PK Parameter: Cmax of GS-3583
Cmax is defined as the maximum observed plasma concentration.
Measured: 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)
Part 1: PK Parameter: Tmax of GS-3583
Tmax is defined as the time to reach maximum observed plasma concentration (Tmax).
Measured: 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)
Part 2: Confirmed Objective Response Rate (ORR)
Confirmed ORR is defined as the percentage of participants who have achieved confirmed CR or PR according to RECIST V1.1 and assessed by the investigator. Per RECIST V1.1, CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: First dose date in Part 2 to End of Study (approximately 4.2 months)
Part 2: Progression-free Survival (PFS)
PFS is defined as the time from first dose date until first date of disease progression (PD) or death from any cause, whichever comes first as measured per RECIST V1.1 as assessed by the investigator. Per RECIST V1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Measured: First dose date in Part 2 to End of Study (approximately 4.2 months)
Part 2: Duration of Response (DOR)
DOR was defined as time of first response (CR or PR) per RECIST V1.1 as assessed by the investigator until the date of first documented disease progression or death, whichever comes first. Per RECIST V1.1, CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Measured: First dose date in Part 2 to End of Study (approximately 4.2 months)
Part 2: Overall Survival (OS)
Overall survival is defined as the time from randomization until death from any cause.
Measured: First dose date in Part 2 to End of Study (approximately 4.2 months)
Part 2: Disease Control Rate (DCR)
DCR was defined as percentage of participants with a best overall confirmed response of CR or PR or stable disease. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Measured: First dose date in Part 2 to End of Study (approximately 4.2 months)
Part 2: PK Parameters: Cmax for GS-3583
Cmax is defined as the maximum observed serum concentration of drug.
Measured: Safety-run In:Cycles 1 and 3: Day 1, predose, EOI; 2, 6 hours, Days 8, 15; Part 2 all arms:Cycles 2 and 5: Day 1 predose, EOI and every odd cycles; 60-day FU; (Cycle length of all cycles = 21 days in Part 2; Infusion duration=60 minutes)
Part 2: PK Parameter: Tmax for GS-3583
Tmax is defined as the time (observed time point) of the occurrence of Cmax.
Measured: Safety-run In: Cycles 1, and 3: Day 1, predose, EOI; 2, 6 hours, Days 8, Day 15; Part 2: all arms: Cycles 2 and 5: Day 1 predose, EOI and every odd cycles; 6-day FU; (Cycle length of all cycles = 21 days in Part 2; Infusion duration=60 minutes)
Part 2: PK Parameter: AUCtau of GS-3583
AUCtau is defined as the area under the concentration versus time curve over the dosing interval.
Measured: Safety-run In: Cycles 1, and 3: Day 1, predose, EOI; 2, 6 hours, Days 8, Day 15; Part 2: all arms: Cycles 2 and 5: Day 1 predose, EOI and every odd cycles; 6-day FU; (Cycle length of all cycles = 21 days in Part 2; Infusion duration=60 minutes)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2021
- Study start25 Mar 2021
- Primary completion7 Nov 2022
- Study completion7 Nov 2022
Why it stopped: Sponsor decision to prematurely discontinue the study, following an internal safety assessment of the molecule, GS-3583.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04747470
- Sponsor's protocol ID
- GS-US-496-5657
- Status last verified
- Aug 2024
- First submitted
- 5 Feb 2021
- Last updated
- 3 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Brody J, Thompson JA, Tolcher AW, Kuhne MR, Huang XR, et al. Phase 1b Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of GS3583, a FLT3 Agonist Fc Fusion Protein, in Patients With Advanced Solid Tumors [Poster TPS3147]. J Clin oncol 2021 June; 39 (15_suppl).
Tolcher AW, Brody J, Rajakumaraswamy N, Lakhani NJ, Kuhne MR, Trowe T, et al. Phase 1b study of GS-3583, a novel FLT3 agonist Fc fusion protein, in patients with advanced solid tumors. [Poster TPS2566]. J Clin oncol 2022 June; 40 (16_suppl).
Dauki AM, Jones A, Singh I, Rajakumaraswamy N, Qin A, et al. Population pharmacokinetics of GS-3583 in healthy volunteers and patients with advanced solid tumors [Poster II-083]. Clin Pharmacol Ther 2023 March; 113 (S5-S100).
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of GS-3583, a FLT3 Agonist Fc Fusion Protein, in Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT04747470
- Acronym / sponsor ID
- GS-US-496-5657
- Conditions
- Advanced Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision to prematurely discontinue the study, following an internal safety assessment of the molecule, GS-3583.
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- 25 Mar 2021 (actual)
- Primary completion
- 7 Nov 2022 (actual)
- Study completion
- 7 Nov 2022 (actual)
- First posted
- 10 Feb 2021 (actual)
- Results
- Posted 3 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 11
| Arm | Type | Receives |
|---|---|---|
| Part 1: Cohort 1: GS-3583 675 μg | Experimental | Drug: GS-3583Participants with advanced solid tumors will receive GS-3583 675 μg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle for up to 13 cycles (up to 52 weeks) or until the participant met study treatment discontinuation criteria. |
| Part 1: Cohort 2: GS-3583 2000 μg | Experimental | Drug: GS-3583Participants with advanced solid tumors will receive GS-3583 2000 μg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle for up to 13 cycles (up to 52 weeks) or until the participant met study treatment discontinuation criteria. |
| Part 1: Cohort 3: GS-3583 6000 μg | Experimental | Drug: GS-3583Participants with advanced solid tumors will receive GS-3583 6000 μg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle for up to 13 cycles (up to 52 weeks) or until the participant met study treatment discontinuation criteria. |
| Part 1: Cohort 4: GS-3583 12000 μg | Experimental | Drug: GS-3583Participants with advanced solid tumors will receive GS-3583 12000 μg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle for up to 13 cycles (up to 52 weeks) or until the participant met study treatment discontinuation criteria. |
| Part 1: Cohort 5: GS-3583 20000 μg | Experimental | Drug: GS-3583Participants with advanced solid tumors will receive GS-3583 20000 μg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle for up to 13 cycles (up to 52 weeks) or until the participant met study treatment discontinuation criteria. |
| Part 2: Safety Run-In Cohort A: GS-3583 + Combination Anticancer Therapy | Experimental | Drug: GS-3583, Drug: Zimberelimab, Drug: Cisplatin, Drug: Carboplatin, Drug: 5-FluorouracilParticipants with head and neck squamous cell carcinoma (HNSCC) will receive GS-3583 at a dose determined in Part 1 on Day 1 of every 21-day cycles for up to 8 cycles + ZIM 360 mg, on Day 1 of each 21-day cycle up to 105 weeks + cisplatin 100 mg/m^2 of BSA on Day 1 of each 21-day cycle up to 6 cycles + carboplatin area under the curve 5 mg/mL/min on Day 1 of each 28- day cycle up to 6 cycles + 5-5-flourouracil (5-FU) 1000 mg/m^2 of BSA/day on Days 1 to 4 of 21-day cycle up to 6 cycles. |
| Part 2: Safety Run-In Cohort B: GS-3583 + Combination Anticancer Therapy | Experimental | Drug: GS-3583, Drug: DocetaxelParticipants with non-small cell lung cancer (NSCLC) will receive GS-3583 at a dose determined in Part 1 on Day 1 of every 21-day cycles for up to 8 cycles + docetaxel 75 mg/m^2 on Day 1 of each 21-day cycle until 1 or more criteria for discontinuation are met. |
| Part 2: Randomized Expansion Cohort A: GS-3583 + Combination Anticancer Therapy | Experimental | Drug: GS-3583, Drug: Zimberelimab, Drug: Cisplatin, Drug: Carboplatin, Drug: 5-FluorouracilParticipants with HNSCC will receive GS-3583 at a dose determined in Part 1 on Day 1 of every 21-day cycles for up to 8 cycles + ZIM 360 mg, on Day 1 of each 21-day cycle up to 105 weeks + cisplatin 100 mg/m^2 of BSA on Day 1 of each 21-day cycle up to 6 cycles + carboplatin area under the curve 5 mg/mL/min on Day 1 of each 21-day cycle up to 6 cycles + 5-FU 1000 mg/m^2 of BSA/day on Days 1 to 4 of 21-day cycle up to 6 cycles. |
| Part 2: Randomized Expansion Cohort A: Combination Anticancer Therapy | Experimental | Drug: Zimberelimab, Drug: Cisplatin, Drug: Carboplatin, Drug: 5-FluorouracilParticipants with HNSCC will receive ZIM 360 mg, on Day 1 of each 21-day cycle up to 105 weeks + cisplatin 100 mg/m^2 of BSA on Day 1 of each 21-day cycle up to 6 cycles + carboplatin area under th e curve 5 mg/mL/min on Day 1 of each 21-day cycle up to 6 cycles + 5-FU 1000 mg/m^2 of BSA/day on Days 1 to 4 of 21-day cycle up to 6 cycles. |
| Part 2: Randomized Expansion Cohort B: GS-3583 + Combination Anticancer Therapy | Experimental | Drug: GS-3583, Drug: DocetaxelParticipants with NSCLC will receive GS-3583 at a dose determined in Part 1 on Day 1 of every 21-day cycles for up to 8 cycles + docetaxel 75 mg/m^2 on Day 1 of each 21-day cycle until 1 or more criteria for discontinuation are met. |
| Part 2: Randomized Expansion Cohort B: Combination Anticancer Therapy | Experimental | Drug: DocetaxelParticipants with NSCLC will receive docetaxel 75 mg/m^2 on Day 1 of each 21-day cycle until 1 or more criteria for discontinuation are met. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Histologically or cytologically confirmed locally advanced or metastatic malignant solid tumor that is refractory to or intolerant of standard therapy or for which no standard therapy is available
- Have measurable disease on imaging based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
- Eastern Cooperative oncology Group (ECOG) performance status of ≤ 2
- Life expectancy of ≥ 3 months, in the opinion of the investigator
- Adequate organ function as assessed by hematological, renal, and hepatic parameters, and no clinically significant coagulopathy
Key exclusion criteria (8 listed)
- Received prior systemic cytotoxic chemotherapy, biological therapy, radiotherapy, or major surgery within 3 weeks of Cycle 1 Day 1; a 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease with sponsor approval
- Known severe hypersensitivity reactions (NCI CTCAE Grade ≥ 3) to fully human monoclonal antibodies or fusion proteins, GS-3583 formulation excipients, or severe reaction to immuno-oncology agents, such as colitis or pneumonitis requiring treatment with corticosteroids, any history of anaphylaxis, or uncontrolled asthma
- Concurrent active malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix, or superficial bladder cancer who has undergone potentially curative therapy with no evidence of disease. Individuals with other previous malignancies are eligible if disease free for > 2 years.
- Previous history of hematological malignancy, monoclonal gammopathy of unknown significance (MGUS) or other preleukemic states (Presence of clonal hematopoiesis of indeterminate potential (CHIP)/age related clonal hematopoiesis (ARCH) is acceptable)
- Known CNS metastasis(es), unless metastases are treated and stable and the individual does not require systemic corticosteroids for management of CNS symptoms at least 1 week prior to study treatment. Individuals with history of carcinomatous meningitis are excluded regardless of clinical stability.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GS-3583Administered as an intravenous (IV) infusion | Drug | Part 1: Cohort 1: GS-3583 675 μg, Part 1: Cohort 2: GS-3583 2000 μg, Part 1: Cohort 3: GS-3583 6000 μg, Part 1: Cohort 4: GS-3583 12000 μg, Part 1: Cohort 5: GS-3583 20000 μg, Part 2: Randomized Expansion Cohort A: GS-3583 + Combination Anticancer Therapy, Part 2: Randomized Expansion Cohort B: GS-3583 + Combination Anticancer Therapy, Part 2: Safety Run-In Cohort A: GS-3583 + Combination Anticancer Therapy, Part 2: Safety Run-In Cohort B: GS-3583 + Combination Anticancer Therapy |
| ZimberelimabAdministered as an IV infusion | Drug | Part 2: Randomized Expansion Cohort A: Combination Anticancer Therapy, Part 2: Randomized Expansion Cohort A: GS-3583 + Combination Anticancer Therapy, Part 2: Safety Run-In Cohort A: GS-3583 + Combination Anticancer Therapy |
| CisplatinAdministered as an IV infusion | Drug | Part 2: Randomized Expansion Cohort A: Combination Anticancer Therapy, Part 2: Randomized Expansion Cohort A: GS-3583 + Combination Anticancer Therapy, Part 2: Safety Run-In Cohort A: GS-3583 + Combination Anticancer Therapy |
| CarboplatinAdministered as an IV infusion | Drug | Part 2: Randomized Expansion Cohort A: Combination Anticancer Therapy, Part 2: Randomized Expansion Cohort A: GS-3583 + Combination Anticancer Therapy, Part 2: Safety Run-In Cohort A: GS-3583 + Combination Anticancer Therapy |
| 5-FluorouracilAdministered as an IV infusion | Drug | Part 2: Randomized Expansion Cohort A: Combination Anticancer Therapy, Part 2: Randomized Expansion Cohort A: GS-3583 + Combination Anticancer Therapy, Part 2: Safety Run-In Cohort A: GS-3583 + Combination Anticancer Therapy |
| DocetaxelAdministered as an IV infusion | Drug | Part 2: Randomized Expansion Cohort B: Combination Anticancer Therapy, Part 2: Randomized Expansion Cohort B: GS-3583 + Combination Anticancer Therapy, Part 2: Safety Run-In Cohort B: GS-3583 + Combination Anticancer Therapy |
Primary outcome
Parts 1 and 2: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
Time frame: 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.
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
Time frame: 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.
Parts 1 and 2: Percentage of Participants With Laboratory Abnormalities According to the NCI CTCAE Version 5.0
Time frame: 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.
Parts 1 and 2: Percentage of Participants With GS-3583 Anti-drug Antibodies (ADAs) at Any Visit
Time frame: 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.
11 secondary outcomes
Part 1: Pharmacokinetic (PK) Parameter: AUCtau of GS-3583
Time frame: 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)
Part 1: PK Parameter: Cmax of GS-3583
Time frame: 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)
Part 1: PK Parameter: Tmax of GS-3583
Time frame: 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)
Part 2: Confirmed Objective Response Rate (ORR)
Time frame: First dose date in Part 2 to End of Study (approximately 4.2 months)
Part 2: Progression-free Survival (PFS)
Time frame: First dose date in Part 2 to End of Study (approximately 4.2 months)
Part 2: Duration of Response (DOR)
Time frame: First dose date in Part 2 to End of Study (approximately 4.2 months)
Part 2: Overall Survival (OS)
Time frame: First dose date in Part 2 to End of Study (approximately 4.2 months)
Part 2: Disease Control Rate (DCR)
Time frame: First dose date in Part 2 to End of Study (approximately 4.2 months)
Part 2: PK Parameters: Cmax for GS-3583
Time frame: Safety-run In:Cycles 1 and 3: Day 1, predose, EOI; 2, 6 hours, Days 8, 15; Part 2 all arms:Cycles 2 and 5: Day 1 predose, EOI and every odd cycles; 60-day FU; (Cycle length of all cycles = 21 days in Part 2; Infusion duration=60 minutes)
Part 2: PK Parameter: Tmax for GS-3583
Time frame: Safety-run In: Cycles 1, and 3: Day 1, predose, EOI; 2, 6 hours, Days 8, Day 15; Part 2: all arms: Cycles 2 and 5: Day 1 predose, EOI and every odd cycles; 6-day FU; (Cycle length of all cycles = 21 days in Part 2; Infusion duration=60 minutes)
Part 2: PK Parameter: AUCtau of GS-3583
Time frame: Safety-run In: Cycles 1, and 3: Day 1, predose, EOI; 2, 6 hours, Days 8, Day 15; Part 2: all arms: Cycles 2 and 5: Day 1 predose, EOI and every odd cycles; 6-day FU; (Cycle length of all cycles = 21 days in Part 2; Infusion duration=60 minutes)
Results and safety
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Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publicationBrody J, Thompson JA, Tolcher AW, Kuhne MR, Huang XR, et al. Phase 1b Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of GS3583, a FLT3 Agonist Fc Fusion Protein, in Patients With Advanced Solid Tumors [Poster TPS3147]. J Clin oncol 2021 June; 39 (15_suppl).
- Results publicationTolcher AW, Brody J, Rajakumaraswamy N, Lakhani NJ, Kuhne MR, Trowe T, et al. Phase 1b study of GS-3583, a novel FLT3 agonist Fc fusion protein, in patients with advanced solid tumors. [Poster TPS2566]. J Clin oncol 2022 June; 40 (16_suppl).
- Results publicationDauki AM, Jones A, Singh I, Rajakumaraswamy N, Qin A, et al. Population pharmacokinetics of GS-3583 in healthy volunteers and patients with advanced solid tumors [Poster II-083]. Clin Pharmacol Ther 2023 March; 113 (S5-S100).
- Gilead Clinical Trials WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gilead Study Director study director
Gilead Sciences
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GS-3583, Zimberelimab and Cisplatin in people with Advanced Solid Tumors, run by Gilead Sciences at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Parts 1 and 2: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) (time frame: Part 1: Day 1 through Day 28; Part 2: Day 1 through Day 21). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04747470, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2024.