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Sponsor decision to prematurely discontinue the study, following an internal safety assessment of the molecule, GS-3583.
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
|
| Part 1: Cohort 5: GS-3583 20000 μg |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GS-3583 | Drug | Administered as an intravenous (IV) infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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) |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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: Other protocol defined Inclusion/Exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Gilead Study Director | Gilead Sciences | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| START Midwest | Grand Rapids | Michigan | 49546 | United States | ||
| Icahn School of Medicine at Mount Sinai |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Result | 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). | ||
| Result | 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). | ||
| Result | 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). |
| Label | URL |
|---|---|
| Gilead Clinical Trials Website | View source |
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22 participants were screened.
Participants were enrolled at study sites in the United States. This study was planned to be conducted in 2 parts: Part 1: Dose Escalation Part and Part 2: Safety Run-In and Randomized Expansion Part. Due to early termination of the study, Part 2 was not conducted. Results are reported only for Part 1 of the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1: Cohort 1: GS-3583 675 μg | Prior to the start of enrollment in this study, the GS-3583 dose of 675 µg was evaluated in healthy volunteers in another study, GS-US-496-5619 and deemed well tolerated, therefore, no participants were enrolled at the planned Cohort 1 dose of 675 µg in this study and this cohort was excluded from the study. The enrolment in the study started in Cohort 2 at a dose of 2000 µg. |
| FG001 | Part 1: Cohort 2: GS-3583 2000 μg | Participants received 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. |
| FG002 | Part 1: Cohort 3: GS-3583 6000 μg | Participants received 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. |
| FG003 | Part 1: Cohort 4: GS-3583 12000 μg | Participants received 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. |
| FG004 | Part 1: Cohort 5: GS-3583 20000 μg | Participants received 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. |
| FG005 | Part 2: Safety Run-In Cohort A: GS-3583 + Combination Anticancer Therapy | Safety Run-In Cohort A of Part 2 were to include participants with head and neck squamous cell carcinoma (HNSCC) to receive GS-3583 at a dose determined in Part 1 on Day 1 of every 21-day cycles for up to 8 cycles + zimberelimab (ZIM) 360 mg, on Day 1 of each 21-day cycle up to 105 weeks + cisplatin 100 mg/m^2 of body surface area (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-flourouracil (5-FU) 1000 mg/m^2 of BSA/day on Days 1 to 4 of 21-day cycle up to 6 cycles. However, as the study was early terminated, no participants were enrolled in Part 2 of the study. |
| FG006 | Part 2: Safety Run-In Cohort B: GS-3583 + Combination Anticancer Therapy | Safety Run-In Cohort B of Part 2 were to include participants with non-small cell lung cancer (NSCLC) to 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. However, as the study was early terminated, no participants were enrolled in Part 2 of the study. |
| FG007 | Part 2: Randomized Expansion Cohort A: GS-3583 + Combination Anticancer Therapy | Safety Run-In Cohort A of Part 2 were to include participants with HNSCC to 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 28- 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-FU 1000 mg/m^2 of BSA/day on Days 1 to 4 of 21-day cycle up to 6 cycles. However, as the study was early terminated, no participants were enrolled in Part 2 of the study. |
| FG008 | Part 2: Randomized Expansion Cohort A: Combination Anticancer Therapy | Randomized Expansion Cohort A of Part 2 were to include participants with HNSCC to 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 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. However, as the study was early terminated, no participants were enrolled in Part 2 of the study. |
| FG009 | Part 2: Randomized Expansion Cohort B: GS-3583 + Combination Anticancer Therapy | Randomized Expansion Cohort B of Part 2 were to include participants with NSCLC to 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. However, as the study was early terminated, no participants were enrolled in Part 2 of the study. |
| FG010 | Part 2: Randomized Expansion Cohort B: Combination Anticancer Therapy | Randomized Expansion Cohort B of Part 2 were to include participants with NSCLC to receive docetaxel 75 mg/m^2 on Day 1 of each 21-day cycle until 1 or more criteria for discontinuation are met. However, as the study was early terminated, no participants were enrolled in Part 2 of the study. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The Safety Analysis Set included all participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1: Cohort 2: GS-3583 2000 μg | Participants received 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 meets study treatment discontinuation criteria. |
| BG001 | Part 1: Cohort 3: GS-3583 6000 μg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | DLT Evaluable Analysis Set included all participants who were enrolled for dose escalation, received all prescribed treatments and completed safety procedures through DLT assessment period (from Day 1 through Day 28 inclusive of the last day) or experienced a DLT prior to end of DLT assessment period as specified in protocol. No participants were enrolled in Part 2, so, data are reported for Part 1 only. | Posted | Number | percentage of participants | Part 1: Day 1 through Day 28; Part 2: Day 1 through Day 21 |
|
Up to 14.8 months
All-Cause Mortality: All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.
Adverse Events: Safety Analysis Set included all participants who received at least 1 dose of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part 1: Cohort 1: GS-3583 675 μg | Prior to the start of enrollment in this study, the GS-3583 dose of 675 µg was evaluated in healthy volunteers in another study, GS-US-496-5619 and deemed well tolerated, therefore, no participants were enrolled at the planned Cohort 1 dose of 675 µg in this study and this cohort was excluded from the study. The enrolment in the study started in Cohort 2 at a dose of 2000 µg. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA version 26.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA version 26.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gilead Clinical Study Information Center | Gilead Sciences | 1-833-445-3230 (GILEAD-0) | GileadClinicalTrials@gilead.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 14, 2022 | Sep 11, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 13, 2023 | Sep 11, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C000719848 | zimberelimab |
| D002945 | Cisplatin |
| D016190 | Carboplatin |
| D005472 | Fluorouracil |
| D000077143 | Docetaxel |
| ID | Term |
|---|---|
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
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| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
|
| Zimberelimab | Drug | Administered as an IV infusion |
|
| Cisplatin | Drug | Administered as an IV infusion |
|
| Carboplatin | Drug | Administered as an IV infusion |
|
| 5-Fluorouracil | Drug | Administered as an IV infusion |
|
| Docetaxel | Drug | Administered as an IV infusion |
|
Participants were monitored for the development of ADAs throughout their treatment period with GS-3583 and at the end of study.
| 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) |
| Part 1: PK Parameter: Cmax of GS-3583 | Cmax is defined as the maximum observed plasma concentration. | 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). | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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) |
| New York |
| New York |
| 10029 |
| United States |
| Oregon Health & Science University | Portland | Oregon | 97239 | United States |
| NEXT oncology | San Antonio | Texas | 78229 | United States |
| Withdrew Consent |
|
| Study Terminated by Sponsor |
|
Participants received 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 meets study treatment discontinuation criteria. |
| BG002 | Part 1: Cohort 4: GS-3583 12000 μg | Participants received 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 meets study treatment discontinuation criteria. |
| BG003 | Part 1: Cohort 5: GS-3583 20000 μg | Participants received 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 meets study treatment discontinuation criteria. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Prior to the start of enrollment in this study, the GS-3583 dose of 675 µg was evaluated in healthy volunteers in another study, GS-US-496-5619 and deemed well tolerated, therefore, no participants were enrolled at the planned Cohort 1 dose of 675 µg in this study and this cohort was excluded from the study. The enrolment in the study started in Cohort 2 at a dose of 2000 µg.
| OG001 | Part 1: Cohort 2: GS-3583 2000 μg | Participants received 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 meets study treatment discontinuation criteria. |
| OG002 | Part 1: Cohort 3: GS-3583 6000 μg | Participants received 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 meets study treatment discontinuation criteria. |
| OG003 | Part 1: Cohort 4: GS-3583 12000 μg | Participants received 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 meets study treatment discontinuation criteria. |
| OG004 | Part 1: Cohort 5: GS-3583 20000 μg | Participants received 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 meets study treatment discontinuation criteria. |
| OG005 | Part 2: Safety Run-In Cohort A: GS-3583 + Combination Anticancer Therapy | Safety Run-In Cohort A of Part 2 were to include participants with HNSCC to 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 28- 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-FU 1000 mg/m^2 of BSA/day on Days 1 to 4 of 21-day cycle up to 6 cycles. However, as the study was early terminated, no participants were enrolled in Part 2 of the study. |
| OG006 | Part 2: Safety Run-In Cohort B: GS-3583 + Combination Anticancer Therapy | Safety Run-In Cohort B of Part 2 were to include participants with NSCLC to 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. However, as the study was early terminated, no participants were enrolled in Part 2 of the study. |
| OG007 | Part 2: Randomized Expansion Cohort A: GS-3583 + Combination Anticancer Therapy | Randomized Expansion Cohort A of Part 2 were to include participants with HNSCC to receive GS-3583 at a dose determined in Part 1 on Day 1 of every 21-day cycles for up to 8 cycles + ZIM (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 28- 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-FU 1000 mg/m^2 of BSA/day on Days 1 to 4 of 21-day cycle up to 6 cycles. However, as the study was early terminated, no participants were enrolled in Part 2 of the study. |
| OG008 | Part 2: Randomized Expansion Cohort A: Combination Anticancer Therapy | Randomized Expansion Cohort A of Part 2 were to include participants with HNSCC to 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 28- 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-FU 1000 mg/m^2 of BSA/day on Days 1 to 4 of 21-day cycle up to 6 cycles. However, as the study was early terminated, no participants were enrolled in Part 2 of the study. |
| OG009 | Part 2: Randomized Expansion Cohort B: GS-3583 + Combination Anticancer Therapy | Randomized Expansion Cohort B of Part 2 were to include participants with NSCLC to 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. However, as the study was early terminated, no participants were enrolled in Part 2 of the study. |
| OG010 | Part 2: Randomized Expansion Cohort B: Combination Anticancer Therapy | Randomized Expansion Cohort B of Part 2 were to include participants with NSCLC to receive docetaxel 75 mg/m^2 on Day 1 of each 21-day cycle until 1 or more criteria for discontinuation are met. However, as the study was early terminated, no participants were enrolled in Part 2 of the study. |
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| Primary | 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. | The Safety Analysis Set included all the participants who received at least 1 dose of study drug. No participants were enrolled in Part 2, so, data are reported for Part 1 only. | Posted | Number | percentage of participants | First dose date up to last dose date plus 90 days (Up to 4 months) |
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| Primary | 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. | The Safety Analysis Set will include all participants who received at least 1 dose of study drug. No participants were enrolled in Part 2, so, data are reported for Part 1 only. | Posted | Number | percentage of participants | First dose date up to last dose date plus 90 days (Up to 4 months) |
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| Primary | 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. | Immunogenicity Analysis Set included all enrolled participants who received at least 1 dose of study drug and have at least 1 non-missing ADA test result. No participants were enrolled in Part 2, so, data are reported for Part 1 only. | Posted | Number | percentage of participants | 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) |
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| Secondary | 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. | The PK Analysis Set included all enrolled participants who received at least 1 dose of study drug and have at least 1 non-missing postdose concentration value reported by the PK laboratory. Data for Cycle 3 is not reported due to participant's confidentiality reasons, as there was only 1 or 2 participants in each of these groups during Cycle 3. | Posted | Mean | Standard Deviation | h*ng/mL | 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) |
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| Secondary | Part 1: PK Parameter: Cmax of GS-3583 | Cmax is defined as the maximum observed plasma concentration. | The PK Analysis Set included all enrolled participants who received at least 1 dose of study drug and have at least 1 non-missing postdose concentration value reported by the PK laboratory. Data for Cycle 3 is not reported due to participant's confidentiality reasons, as there was only 1 or 2 participants in each of these groups during Cycle 3. | Posted | Mean | Standard Deviation | ng/mL | 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) |
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| Secondary | Part 1: PK Parameter: Tmax of GS-3583 | Tmax is defined as the time to reach maximum observed plasma concentration (Tmax). | The PK Analysis Set included all enrolled participants who received at least 1 dose of study drug and have at least 1 non-missing postdose concentration value reported by the PK laboratory. Data for Cycle 3 is not reported due to participant's confidentiality reasons, as there was only 1 or 2 participants in each of these groups during Cycle 3. | Posted | Median | Full Range | hours (h) | 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) |
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| Secondary | 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. | No participants were enrolled in Part 2 of the study, so, data was not collected for this outcome measure. | Posted | First dose date in Part 2 to End of Study (approximately 4.2 months) |
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| Secondary | 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. | No participants were enrolled in Part 2 of the study, so, data was not collected for this outcome measure. | Posted | First dose date in Part 2 to End of Study (approximately 4.2 months) |
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| Secondary | 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. | No participants were enrolled in Part 2 of the study, so, data was not collected for this outcome measure. | Posted | First dose date in Part 2 to End of Study (approximately 4.2 months) |
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| Secondary | Part 2: Overall Survival (OS) | Overall survival is defined as the time from randomization until death from any cause. | No participants were enrolled in Part 2 of the study, so, data was not collected for this outcome measure. | Posted | First dose date in Part 2 to End of Study (approximately 4.2 months) |
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| Secondary | 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. | No participants were enrolled in Part 2 of the study, so, data was not collected for this outcome measure. | Posted | First dose date in Part 2 to End of Study (approximately 4.2 months) |
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| Secondary | Part 2: PK Parameters: Cmax for GS-3583 | Cmax is defined as the maximum observed serum concentration of drug. | No participants were enrolled in Part 2 of the study, so, data was not collected for this outcome measure. | Posted | 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) |
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| Secondary | Part 2: PK Parameter: Tmax for GS-3583 | Tmax is defined as the time (observed time point) of the occurrence of Cmax. | No participants were enrolled in Part 2 of the study, so, data was not collected for this outcome measure. | Posted | 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) |
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| Secondary | Part 2: PK Parameter: AUCtau of GS-3583 | AUCtau is defined as the area under the concentration versus time curve over the dosing interval. | No participants were enrolled in Part 2 of the study, so, data was not collected for this outcome measure. | Posted | 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) |
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| 0 |
| 0 |
| 0 |
| 0 |
| 0 |
| 0 |
| EG001 | Part 1: Cohort 2: GS-3583 2000 μg | Participants received 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 meets study treatment discontinuation criteria. | 3 | 3 | 2 | 3 | 3 | 3 |
| EG002 | Part 1: Cohort 3: GS-3583 6000 μg | Participants received 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 meets study treatment discontinuation criteria. | 2 | 3 | 1 | 3 | 3 | 3 |
| EG003 | Part 1: Cohort 4: GS-3583 12000 μg | Participants received 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 meets study treatment discontinuation criteria. | 2 | 3 | 2 | 3 | 3 | 3 |
| EG004 | Part 1: Cohort 5: GS-3583 20000 μg | Participants received 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 meets study treatment discontinuation criteria. | 2 | 4 | 1 | 4 | 4 | 4 |
| EG005 | Part 2: Safety Run-In Cohort A: GS-3583 + Combination Anticancer Therapy | Safety Run-In Cohort A of Part 2 were to include participants with HNSCC to 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 28- 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-FU 1000 mg/m^2 of BSA/day on Days 1 to 4 of 21-day cycle up to 6 cycles. However, as the study was early terminated, no participants were enrolled in Part 2 of the study. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG006 | Part 2: Safety Run-In Cohort B: GS-3583 + Combination Anticancer Therapy | Safety Run-In Cohort B of Part 2 were to include participants with NSCLC to 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. However, as the study was early terminated, no participants were enrolled in Part 2 of the study. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG007 | Part 2: Randomized Expansion Cohort A: GS-3583 + Combination Anticancer Therapy | Safety Run-In Cohort A of Part 2 were to include participants with HNSCC to 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 28- 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-FU 1000 mg/m^2 of BSA/day on Days 1 to 4 of 21-day cycle up to 6 cycles. However, as the study was early terminated, no participants were enrolled in Part 2 of the study. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG008 | Part 2: Randomized Expansion Cohort A: Combination Anticancer Therapy | Randomized Expansion Cohort A of Part 2 were to include participants with HNSCC to 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 28- 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-FU 1000 mg/m^2 of BSA/day on Days 1 to 4 of 21-day cycle up to 6 cycles. However, as the study was early terminated, no participants were enrolled in Part 2 of the study. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG009 | Part 2: Randomized Expansion Cohort B: GS-3583 + Combination Anticancer Therapy | Randomized Expansion Cohort B of Part 2 were to include participants with NSCLC to 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. However, as the study was early terminated, no participants were enrolled in Part 2 of the study. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG010 | Part 2: Randomized Expansion Cohort B: Combination Anticancer Therapy | Randomized Expansion Cohort B of Part 2 were to include participants with NSCLC to receive docetaxel 75 mg/m^2 on Day 1 of each 21-day cycle until 1 or more criteria for discontinuation are met. However, as the study was early terminated, no participants were enrolled in Part 2 of the study. | 0 | 0 | 0 | 0 | 0 | 0 |
| Large intestinal obstruction | Gastrointestinal disorders | MedDRA version 26.0 | Systematic Assessment |
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| Small intestinal obstruction | Gastrointestinal disorders | MedDRA version 26.0 | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA version 26.0 | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA version 26.0 | Systematic Assessment |
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| Second primary malignancy | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 26.0 | Systematic Assessment |
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| Cerebrovascular accident | Nervous system disorders | MedDRA version 26.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA version 26.0 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA version 26.0 | Systematic Assessment |
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| Ascites | Gastrointestinal disorders | MedDRA version 26.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA version 26.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA version 26.0 | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA version 26.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA version 26.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA version 26.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA version 26.0 | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA version 26.0 | Systematic Assessment |
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| Pain | General disorders | MedDRA version 26.0 | Systematic Assessment |
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| Hypertransaminasaemia | Hepatobiliary disorders | MedDRA version 26.0 | Systematic Assessment |
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| Bacteraemia | Infections and infestations | MedDRA version 26.0 | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA version 26.0 | Systematic Assessment |
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| Covid-19 | Infections and infestations | MedDRA version 26.0 | Systematic Assessment |
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| Oral candidiasis | Infections and infestations | MedDRA version 26.0 | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | MedDRA version 26.0 | Systematic Assessment |
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| Blood bilirubin increased | Investigations | MedDRA version 26.0 | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA version 26.0 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA version 26.0 | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA version 26.0 | Systematic Assessment |
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| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA version 26.0 | Systematic Assessment |
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| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 26.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA version 26.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA version 26.0 | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA version 26.0 | Systematic Assessment |
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| Mental status changes | Psychiatric disorders | MedDRA version 26.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 26.0 | Systematic Assessment |
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| Night sweats | Skin and subcutaneous tissue disorders | MedDRA version 26.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version 26.0 | Systematic Assessment |
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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:
| D056831 |
| Coordination Complexes |
| D009930 | Organic Chemicals |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
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| Cycle 3 |
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| Cycle 3 |
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| Cycle 3 |
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