Advanced Solid Tumors
Conditions
Brief summary
For Phase 1a Part A, the primary objectives are to assess safety and tolerability and to define the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of dalutrafusp alfa (formerly GS-1423) monotherapy in participants with advanced solid tumors. For Phase 1a Part B, the primary objective is to assess safety and tolerability of dalutrafusp alfa monotherapy in participants with advanced solid tumors. For Phase 1b Cohort 1 safety run-in, the primary objective is to assess safety and tolerability and to define the DLT and MTD or RP2D of dalutrafusp alfa in combination with a chemotherapy regimen in participants with advanced gastric or gastroesophageal junction adenocarcinoma. For Phase 1b Cohort 1 post safety run-in, the primary objective is to assess the preliminary efficacy of dalutrafusp alfa in combination with a chemotherapy regimen in participants with advanced gastric or gastroesophageal junction adenocarcinoma, as assessed by the confirmed objective response rate (ORR). For Phase 1b Cohort 2, the primary objective is to assess safety and tolerability of dalutrafusp alfa monotherapy in participants with advanced solid tumors.
Interventions
DRUGDalutrafusp alfa
Administered intravenously
DRUGmFOLFOX6 Regimen
Chemotherapy regimen of oxaliplatin, 5-fluorouracil \[5-FU\], and leucovorin
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Diagnosis: * For Phase 1a and Phase 1b Cohort 2, have a histologically or cytologically confirmed diagnosis of a locally advanced or metastatic solid tumor for which no standard therapy is available (per local guidance) or standard therapy has failed, or * For Phase 1b Cohort 1, have histologically or cytologically confirmed unresectable, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma who have not previously received systemic therapy for advanced disease * Measurable disease: Have measurable disease on imaging based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 * Have a life expectancy of at least 3 months and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Key
Exclusion criteria
* Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 3 weeks of the first dose of treatment * Has persisting toxicity related to prior therapy of National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE) Grade \>1 severity * Is expected to require any other form of systemic or localized anticancer therapy while on trial (including maintenance therapy with another agent, radiation therapy, and/or surgical resection) * Has 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 * Has a known central nervous system metastasis(es), unless metastases are treated and stable and the individual does not require systemic corticosteroids for management of CNS symptoms at least 7 days prior to study treatment. Individuals with history of carcinomatous meningitis are excluded regardless of clinical stability. * Has active or history of autoimmune disease that has required systemic treatment within 2 years of the start of trial treatment Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a Part A: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs), Graded Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | Baseline up to 28 days | DLT was defined as: Grade 3 thrombocytopenia with bleeding; Grade ≥ 3 febrile neutropenia; any Grade 4 hematologic laboratory abnormalities/adverse events (AEs) (except Grade 4 lymphopenia and anaemia, Grade 4 neutropenia lasting ≤ 7 days with no fever); Grade 4 non-hematologic AEs; any ≥Grade 2 uveitis, blurred vision, eye pain, and/or reduction of visual acuity that did not respond to topical therapy and did not improve to Grade 1 severity within 2 weeks of topical therapy initiation or required systemic treatment; Grade 3 non-hematologic AEs; any other non-immune-related Grade 3 AE (except any Grade 3 endocrinopathy; Grade 3 AE of tumor flare; transient \[≤ 3 days\] Grade 3 fatigue, local reactions, headache, nausea, emesis, or diarrhea and/or resolved to Grade ≤ 1; transient Grade 3 flu-like symptoms or fever); inability to receive first 2 doses of GS-1423 or \> 2-week delay in starting next cycle of therapy due to a treatment-related toxicity; Grade 5 event (death). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | First dose date up to permanent withdrawal of GS-1423 (maximum duration: 26.3 weeks) plus 30 days | The Baseline value was the last available value collected on or prior to first dose of study drug. Percentages were based on participants with values available at both baseline and postbaseline. NCS = Non-clinical significance; CS = Clinical significance. |
| Phase 1a Part A: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | First dose date up to permanent withdrawal of GS-1423 (maximum duration: 26.3 weeks) plus 30 days | An AE was any untoward medical occurrence in a participant administered the study drug, which did not necessarily have a causal relationship with the treatment. An AE could therefore, be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Adverse events might also include pretreatment or posttreatment complications that occurred as a result of protocol-specified procedures or special situations. Preexisting events that increased in severity or change in nature during or as a consequence of participation in the study were also considered AEs. TEAEs were AEs with onset dates on or after the first dose of study drug GS-1423 and up to 30 days after permanent withdrawal of GS-1423. |
| Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | First dose date up to permanent withdrawal of GS-1423 (maximum duration: 26.3 weeks) plus 30 days | Severity was graded per NCI CTCAE v5.0. Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe, Grade 4: Life-threatening or disabling, Grade 5: Death related to AE. |
| Phase 1a Part A: Pharmacokinetic (PK) Parameter: AUCtau of GS-1423 | Cycle 1 and Cycle 4: Day 1 (Predose, end of infusion, 2 and 6 hours post start of infusion); Days 2, 3, 5, and 8 (additionally at Day 15 in Cycle 4) | AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). |
| Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Baseline, during the treatment (maximum duration: 26.3 weeks), Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 4 Day 15, Cycle 6 Day 1, 30-day follow-up (30 days after discontinuation of GS-1423), post treatment follow-up (3 months) | — |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at study sites in United States. The first participant was screened on 03 June 2019. The last study visit occurred on 15 April 2021.
Pre-assignment details
The study was discontinued prior to initiation of Phase 1a Part B and Phase 1b. Therefore, data are reported for only Phase 1a Part A.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg GS-1423 0.3 mg/kg of body weight, solution for IV infusion, administered over approximately 60 minutes, on Day 1 of each 2-week cycle until the participant met study treatment discontinuation criteria or for up to 1 year. | 1 |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg GS-1423 1 mg/kg of body weight, solution for IV infusion, administered over approximately 60 minutes, on Day 1 of each 2-week cycle until the participant met study treatment discontinuation criteria or for up to 1 year. | 1 |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg GS-1423 3 mg/kg of body weight, solution for IV infusion, administered over approximately 60 minutes, on Day 1 of each 2-week cycle until the participant met study treatment discontinuation criteria or for up to 1 year. | 3 |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg GS-1423 10 mg/kg of body weight, solution for IV infusion, administered over approximately 60 minutes, on Day 1 of each 2-week cycle until the participant met study treatment discontinuation criteria or for up to 1 year. | 3 |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg GS-1423 20 mg/kg of body weight, solution for IV infusion, administered over approximately 60 minutes, on Day 1 of each 2-week cycle until the participant met study treatment discontinuation criteria or for up to 1 year. | 3 |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg GS-1423 30 mg/kg of body weight, solution for IV infusion, administered over approximately 60 minutes, on Day 1 of each 2-week cycle until the participant met study treatment discontinuation criteria or for up to 1 year. | 7 |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg GS-1423 45 mg/kg of body weight, solution for IV infusion, administered over approximately 60 minutes, on Day 1 of each 2-week cycle until the participant met study treatment discontinuation criteria or for up to 1 year. | 3 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 1 | 1 | 1 | 3 | 2 | 2 | 0 |
| Overall Study | Enrolled but not Treated | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Study Terminated by Sponsor | 0 | 0 | 1 | 0 | 1 | 4 | 2 |
| Overall Study | Withdrew Consent | 0 | 0 | 1 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 58 years | 67 years | 70 years STANDARD_DEVIATION 8.7 | 70 years STANDARD_DEVIATION 11.6 | 62 years STANDARD_DEVIATION 7.4 | 57 years STANDARD_DEVIATION 15.8 | 71 years STANDARD_DEVIATION 7.2 | 64 years STANDARD_DEVIATION 12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 5 Participants | 2 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 3 Participants | 3 Participants | 2 Participants | 5 Participants | 3 Participants | 18 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 3 Participants | 2 Participants | 2 Participants | 6 Participants | 1 Participants | 15 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 1 / 1 | 1 / 3 | 3 / 3 | 2 / 3 | 2 / 8 | 0 / 3 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 3 / 3 | 3 / 3 | 3 / 3 | 7 / 7 | 3 / 3 |
| serious Total, serious adverse events | 0 / 1 | 1 / 1 | 0 / 3 | 2 / 3 | 2 / 3 | 4 / 7 | 0 / 3 |
Outcome results
Primary
Phase 1a Part A: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs), Graded Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0)
DLT was defined as: Grade 3 thrombocytopenia with bleeding; Grade ≥ 3 febrile neutropenia; any Grade 4 hematologic laboratory abnormalities/adverse events (AEs) (except Grade 4 lymphopenia and anaemia, Grade 4 neutropenia lasting ≤ 7 days with no fever); Grade 4 non-hematologic AEs; any ≥Grade 2 uveitis, blurred vision, eye pain, and/or reduction of visual acuity that did not respond to topical therapy and did not improve to Grade 1 severity within 2 weeks of topical therapy initiation or required systemic treatment; Grade 3 non-hematologic AEs; any other non-immune-related Grade 3 AE (except any Grade 3 endocrinopathy; Grade 3 AE of tumor flare; transient \[≤ 3 days\] Grade 3 fatigue, local reactions, headache, nausea, emesis, or diarrhea and/or resolved to Grade ≤ 1; transient Grade 3 flu-like symptoms or fever); inability to receive first 2 doses of GS-1423 or \> 2-week delay in starting next cycle of therapy due to a treatment-related toxicity; Grade 5 event (death).
Time frame: Baseline up to 28 days
Population: The DLT-Evaluable Analysis Set included all participants who were enrolled for dose escalation, received the protocol-specified treatment, and completed safety procedures through Day 28 (inclusive) or experienced a DLT prior to Day 28.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs), Graded Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs), Graded Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | 0 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs), Graded Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | 0 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs), Graded Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | 0 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs), Graded Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | 0 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs), Graded Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs), Graded Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) | 0 percentage of participants |
Secondary
Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs)
Time frame: Baseline, during the treatment (maximum duration: 26.3 weeks), Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 4 Day 15, Cycle 6 Day 1, 30-day follow-up (30 days after discontinuation of GS-1423), post treatment follow-up (3 months)
Population: The Immunogenicity Analysis Set included all participants in the Safety Analysis Set who have at least 1 nonmissing postdose ADA status reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | During the Treatment | 100.0 percentage of participants |
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 3 Day 1 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 4 Day 15 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 4 Day 1 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Baseline | 0 percentage of participants |
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Post Treatment Follow-Up (3 months) | 0 percentage of participants |
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | 30-Day Follow-Up | 100.0 percentage of participants |
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 2 Day 1 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 6 Day 1 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 2 Day 1 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 3 Day 1 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Baseline | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 4 Day 1 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | 30-Day Follow-Up | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 4 Day 15 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Post Treatment Follow-Up (3 months) | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | During the Treatment | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 6 Day 1 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 6 Day 1 | 33.3 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 4 Day 15 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Post Treatment Follow-Up (3 months) | 0 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | During the Treatment | 66.7 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 2 Day 1 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | 30-Day Follow-Up | 0 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 3 Day 1 | 33.3 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Baseline | 0 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 4 Day 1 | 33.3 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Baseline | 0 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | 30-Day Follow-Up | 0 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 6 Day 1 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | During the Treatment | 66.7 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Post Treatment Follow-Up (3 months) | 0 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 4 Day 15 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 2 Day 1 | 66.7 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 4 Day 1 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 3 Day 1 | 33.3 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 6 Day 1 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Baseline | 0 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | During the Treatment | 66.7 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 2 Day 1 | 33.3 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 3 Day 1 | 66.7 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 4 Day 1 | 33.3 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 4 Day 15 | 33.3 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | 30-Day Follow-Up | 33.3 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Post Treatment Follow-Up (3 months) | 33.0 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 6 Day 1 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Post Treatment Follow-Up (3 months) | 0 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | During the Treatment | 0 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 4 Day 1 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Baseline | 14.3 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 3 Day 1 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | 30-Day Follow-Up | 0 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 2 Day 1 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 4 Day 15 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | During the Treatment | 33.3 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 3 Day 1 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 6 Day 1 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 2 Day 1 | 33.3 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 4 Day 1 | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Baseline | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | 30-Day Follow-Up | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Post Treatment Follow-Up (3 months) | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) | Cycle 4 Day 15 | 0 percentage of participants |
Secondary
Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study
The Baseline value was the last available value collected on or prior to first dose of study drug. Percentages were based on participants with values available at both baseline and postbaseline. NCS = Non-clinical significance; CS = Clinical significance.
Time frame: First dose date up to permanent withdrawal of GS-1423 (maximum duration: 26.3 weeks) plus 30 days
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal NCS Baseline - Normal | 0 percentage of participants |
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal CS Baseline - Normal | 0 percentage of participants |
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Normal baseline - Abnormal CS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal NCS Baseline - Abnormal NCS | 100.0 percentage of participants |
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal CS Baseline - Abnormal NCS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal NCS Baseline - Abnormal CS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal CS Baseline - Abnormal CS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Normal baseline - Abnormal NCS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Normal baseline - Normal | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal NCS Baseline - Abnormal CS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal NCS Baseline - Abnormal NCS | 100.0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal CS Baseline - Abnormal CS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Normal baseline - Abnormal NCS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal CS Baseline - Abnormal NCS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Normal baseline - Abnormal CS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Normal baseline - Normal | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal CS Baseline - Normal | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal NCS Baseline - Normal | 0 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal CS Baseline - Normal | 0 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal NCS Baseline - Abnormal NCS | 66.7 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Normal baseline - Normal | 33.3 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Normal baseline - Abnormal NCS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal NCS Baseline - Abnormal CS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal CS Baseline - Abnormal NCS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal NCS Baseline - Normal | 0 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Normal baseline - Abnormal CS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal CS Baseline - Abnormal CS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal NCS Baseline - Abnormal CS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Normal baseline - Normal | 33.3 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Normal baseline - Abnormal NCS | 33.3 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Normal baseline - Abnormal CS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal NCS Baseline - Normal | 0 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal NCS Baseline - Abnormal NCS | 33.3 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal CS Baseline - Normal | 0 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal CS Baseline - Abnormal NCS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal CS Baseline - Abnormal CS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal CS Baseline - Abnormal NCS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal NCS Baseline - Normal | 0 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Normal baseline - Normal | 0 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Normal baseline - Abnormal CS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal NCS Baseline - Abnormal NCS | 33.3 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal CS Baseline - Abnormal CS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal CS Baseline - Normal | 0 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal NCS Baseline - Abnormal CS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Normal baseline - Abnormal NCS | 66.7 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Normal baseline - Abnormal NCS | 71.4 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal NCS Baseline - Normal | 0 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal CS Baseline - Abnormal NCS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Normal baseline - Normal | 0 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal CS Baseline - Normal | 0 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Normal baseline - Abnormal CS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal NCS Baseline - Abnormal NCS | 28.6 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal CS Baseline - Abnormal CS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal NCS Baseline - Abnormal CS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Normal baseline - Abnormal NCS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal NCS Baseline - Abnormal CS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Normal baseline - Abnormal CS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal CS Baseline - Normal | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal NCS Baseline - Normal | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal CS Baseline - Abnormal NCS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Normal baseline - Normal | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal CS Baseline - Abnormal CS | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study | Abnormal NCS Baseline - Abnormal NCS | 100.0 percentage of participants |
Secondary
Phase 1a Part A: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
An AE was any untoward medical occurrence in a participant administered the study drug, which did not necessarily have a causal relationship with the treatment. An AE could therefore, be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Adverse events might also include pretreatment or posttreatment complications that occurred as a result of protocol-specified procedures or special situations. Preexisting events that increased in severity or change in nature during or as a consequence of participation in the study were also considered AEs. TEAEs were AEs with onset dates on or after the first dose of study drug GS-1423 and up to 30 days after permanent withdrawal of GS-1423.
Time frame: First dose date up to permanent withdrawal of GS-1423 (maximum duration: 26.3 weeks) plus 30 days
Population: The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 100.0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 100.0 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 100.0 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 100.0 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 100.0 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 100.0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 100.0 percentage of participants |
Secondary
Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities
Severity was graded per NCI CTCAE v5.0. Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe, Grade 4: Life-threatening or disabling, Grade 5: Death related to AE.
Time frame: First dose date up to permanent withdrawal of GS-1423 (maximum duration: 26.3 weeks) plus 30 days
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Coagulation | 0 percentage of participants |
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Hematology | 0 percentage of participants |
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Urinalysis | 0 percentage of participants |
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Serum Chemistry | 0 percentage of participants |
| Phase 1a (Part A) Cohort 1: GS-1423 0.3 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Endocrine Function Tests | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Coagulation | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Serum Chemistry | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Endocrine Function Tests | 0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Hematology | 100.0 percentage of participants |
| Phase 1a (Part A) Cohort 2: GS-1423 1 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Urinalysis | 0 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Urinalysis | 0 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Serum Chemistry | 0 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Hematology | 0 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Coagulation | 0 percentage of participants |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Endocrine Function Tests | 0 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Coagulation | 0 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Hematology | 0 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Serum Chemistry | 33.3 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Endocrine Function Tests | 0 percentage of participants |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Urinalysis | 0 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Hematology | 33.3 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Urinalysis | 0 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Coagulation | 0 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Endocrine Function Tests | 0 percentage of participants |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Serum Chemistry | 33.3 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Hematology | 14.3 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Urinalysis | 0 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Endocrine Function Tests | 0 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Serum Chemistry | 14.3 percentage of participants |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Coagulation | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Endocrine Function Tests | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Serum Chemistry | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Coagulation | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Hematology | 0 percentage of participants |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities | Urinalysis | 0 percentage of participants |
Secondary
Phase 1a Part A: Pharmacokinetic (PK) Parameter: AUCtau of GS-1423
AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time frame: Cycle 1 and Cycle 4: Day 1 (Predose, end of infusion, 2 and 6 hours post start of infusion); Days 2, 3, 5, and 8 (additionally at Day 15 in Cycle 4)
Population: Participants in the PK Analysis Set (all enrolled participants who received at least 1 dose of study drug and had at least 1 non-missing postdose concentration value reported by the PK laboratory) with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Pharmacokinetic (PK) Parameter: AUCtau of GS-1423 | Cycle 1 | 1476.9 µg*h/mL | Standard Deviation 759.84 |
| Phase 1a (Part A) Cohort 3: GS-1423 3 mg/kg | Phase 1a Part A: Pharmacokinetic (PK) Parameter: AUCtau of GS-1423 | Cycle 4 | 1711.9 µg*h/mL | Standard Deviation 1486.08 |
| Phase 1a (Part A) Cohort 4: GS-1423 10 mg/kg | Phase 1a Part A: Pharmacokinetic (PK) Parameter: AUCtau of GS-1423 | Cycle 1 | 5311.8 µg*h/mL | Standard Deviation 595.77 |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Pharmacokinetic (PK) Parameter: AUCtau of GS-1423 | Cycle 4 | 28558.0 µg*h/mL | — |
| Phase 1a (Part A) Cohort 5: GS-1423 20 mg/kg | Phase 1a Part A: Pharmacokinetic (PK) Parameter: AUCtau of GS-1423 | Cycle 1 | 33530.9 µg*h/mL | Standard Deviation 1646.22 |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Pharmacokinetic (PK) Parameter: AUCtau of GS-1423 | Cycle 1 | 51593.2 µg*h/mL | Standard Deviation 16313.2 |
| Phase 1a (Part A) Cohort 6: GS-1423 30 mg/kg | Phase 1a Part A: Pharmacokinetic (PK) Parameter: AUCtau of GS-1423 | Cycle 4 | 65368.1 µg*h/mL | Standard Deviation 5469.82 |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Pharmacokinetic (PK) Parameter: AUCtau of GS-1423 | Cycle 4 | 74097.0 µg*h/mL | — |
| Phase 1a (Part A) Cohort 7: GS-1423 45 mg/kg | Phase 1a Part A: Pharmacokinetic (PK) Parameter: AUCtau of GS-1423 | Cycle 1 | 64856.3 µg*h/mL | Standard Deviation 9814.95 |