Trial Outcomes & Findings for Study to Assess the Effects of GS-3583 in Participants With Advanced Solid Tumors (NCT NCT04747470)

Last Updated: 2024-09-03

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

13 participants

Primary outcome timeframe

Part 1: Day 1 through Day 28; Part 2: Day 1 through Day 21

Results posted on

2024-09-03

Participant Flow

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.

22 participants were screened.

Participant milestones

Participant milestones
Measure	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.	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.	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.	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.
Overall Study STARTED	3	3	3	4
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	3	3	3	4

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	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.	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.
Overall Study Death	3	2	2	2
Overall Study Withdrew Consent	0	0	1	0
Overall Study Study Terminated by Sponsor	0	1	0	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: Cohort 2: GS-3583 2000 μg n=3 Participants 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.	Part 1: Cohort 3: GS-3583 6000 μg n=3 Participants 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.	Part 1: Cohort 4: GS-3583 12000 μg n=3 Participants 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.	Part 1: Cohort 5: GS-3583 20000 μg n=4 Participants 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.	Total n=13 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	9 Participants n=21 Participants
Age, Continuous	72 years STANDARD_DEVIATION 1.2 • n=5 Participants	63 years STANDARD_DEVIATION 17.6 • n=7 Participants	58 years STANDARD_DEVIATION 15.3 • n=5 Participants	70 years STANDARD_DEVIATION 7.5 • n=4 Participants	66 years STANDARD_DEVIATION 11.8 • n=21 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	6 Participants n=21 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	7 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	9 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	12 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	3 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	4 participants n=4 Participants	13 participants n=21 Participants

PRIMARY outcome

Timeframe: Part 1: Day 1 through Day 28; Part 2: Day 1 through Day 21

Population: 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.

Outcome measures

Outcome measures
Measure	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.	Part 1: Cohort 2: GS-3583 2000 μg n=3 Participants 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.	Part 1: Cohort 3: GS-3583 6000 μg n=3 Participants 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.	Part 1: Cohort 4: GS-3583 12000 μg n=3 Participants 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.	Part 1: Cohort 5: GS-3583 20000 μg n=3 Participants 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.	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.	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.	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.	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.	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.	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.
Parts 1 and 2: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)	—	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	—	—	—	—	—	—

PRIMARY outcome

Timeframe: First dose date up to last dose date plus 90 days (Up to 4 months)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	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.	Part 1: Cohort 2: GS-3583 2000 μg n=3 Participants 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.	Part 1: Cohort 3: GS-3583 6000 μg n=3 Participants 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.	Part 1: Cohort 4: GS-3583 12000 μg n=3 Participants 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.	Part 1: Cohort 5: GS-3583 20000 μg n=4 Participants 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.	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.	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.	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.	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.	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.	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.
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	—	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants	—	—	—	—	—	—

PRIMARY outcome

Timeframe: First dose date up to last dose date plus 90 days (Up to 4 months)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	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.	Part 1: Cohort 2: GS-3583 2000 μg n=3 Participants 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.	Part 1: Cohort 3: GS-3583 6000 μg n=3 Participants 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.	Part 1: Cohort 4: GS-3583 12000 μg n=3 Participants 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.	Part 1: Cohort 5: GS-3583 20000 μg n=4 Participants 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.	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.	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.	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.	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.	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.	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.
Parts 1 and 2: Percentage of Participants With Laboratory Abnormalities According to the NCI CTCAE Version 5.0	—	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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)

Population: 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.

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

Outcome measures

Outcome measures
Measure	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.	Part 1: Cohort 2: GS-3583 2000 μg n=3 Participants 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.	Part 1: Cohort 3: GS-3583 6000 μg n=3 Participants 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.	Part 1: Cohort 4: GS-3583 12000 μg n=3 Participants 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.	Part 1: Cohort 5: GS-3583 20000 μg n=4 Participants 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.	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.	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.	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.	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.	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.	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.
Parts 1 and 2: Percentage of Participants With GS-3583 Anti-drug Antibodies (ADAs) at Any Visit	—	33.3 percentage of participants	33.3 percentage of participants	0 percentage of participants	0 percentage of participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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.

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

Outcome measures

Outcome measures
Measure	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.	Part 1: Cohort 2: GS-3583 2000 μg n=3 Participants 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.	Part 1: Cohort 3: GS-3583 6000 μg n=3 Participants 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.	Part 1: Cohort 4: GS-3583 12000 μg n=3 Participants 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.	Part 1: Cohort 5: GS-3583 20000 μg n=4 Participants 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.	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.	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.	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.	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.	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.	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.
Part 1: Pharmacokinetic (PK) Parameter: AUCtau of GS-3583 Cycle 1	—	82100 h*ng/mL Standard Deviation 19900	249000 h*ng/mL Standard Deviation 124000	352000 h*ng/mL Standard Deviation 41300	832000 h*ng/mL Standard Deviation 223000	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycles 1 and 3,pre-dose,EOI;2, 6 hours;Days 2, 3, 5, 8, 15 post Day 1 EOI;Day 15:Cycle 1:predose and EOI;2 hours post EOI;Cycle 3:336 hours and Day 24 post EOI (Cycle length for all cycles=28 days in Part 1;Infusion duration=60 minutes)

Cmax is defined as the maximum observed plasma concentration.

Outcome measures

Outcome measures
Measure	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.	Part 1: Cohort 2: GS-3583 2000 μg n=3 Participants 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.	Part 1: Cohort 3: GS-3583 6000 μg n=3 Participants 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.	Part 1: Cohort 4: GS-3583 12000 μg n=3 Participants 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.	Part 1: Cohort 5: GS-3583 20000 μg n=4 Participants 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.	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.	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.	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.	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.	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.	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.
Part 1: PK Parameter: Cmax of GS-3583 Cycle 1	—	643 ng/mL Standard Deviation 36.3	1860 ng/mL Standard Deviation 562	2520 ng/mL Standard Deviation 244	5800 ng/mL Standard Deviation 1460	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycles 1 and 3, pre-dose, EOI; 2, 6 hours; Days 2, 3, 5, 8, 15 post Day 1 EOI; Day 15:Cycle 1:predose and EOI; 2 hours post EOI; Cycle 3:336 hours and Day 24 post EOI (Cycle length for all cycles=28 days in Part 1; infusion duration=60 minutes)

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