Clinical Trials /

Safety, Tolerability, Pharmacokinetics, and Efficacy of GS-4224 in Participants With Advanced Solid Tumors

NCT04049617

Description:

The primary objectives of this study are to characterize the safety and tolerability of GS-4224 and to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of GS-4224 in participants with advanced solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety, Tolerability, Pharmacokinetics, and Efficacy of GS-4224 in Participants With Advanced Solid Tumors
  • Official Title: A Phase 1b/2 Dose Escalation/Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of GS-4224 in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: GS-US-494-5484
  • NCT ID: NCT04049617

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
GS-4224GS-4224

Purpose

The primary objectives of this study are to characterize the safety and tolerability of GS-4224 and to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of GS-4224 in participants with advanced solid tumors.

Trial Arms

NameTypeDescriptionInterventions
GS-4224ExperimentalDose Escalation (Phase 1b): Participants will be sequentially enrolled in a dose escalation design to receive GS-4224 starting at ≤ 400 mg. Subsequent doses of ≤700 mg and ≤ 1000 mg are planned based on safety and tolerability of each dose level. Dose Expansion (Phase 2): Dose expansion will begin when the RP2D has been determined.
  • GS-4224

Eligibility Criteria

        Key Inclusion Criteria:

          -  Dose Escalation Cohorts: Histologically or cytologically confirmed advanced malignant
             solid tumor that is refractory to or intolerant of all standard therapy or for which
             no standard therapy is available.

          -  Dose Expansion Cohort: Individuals must have available sufficient and adequate
             formalin fixed tumor sample preferably from a biopsy of a tumor lesion obtained either
             at the time of or after the diagnosis of advanced disease has been made and from a
             site not previously irradiated. Alternatively, individuals must agree to have a biopsy
             taken prior to entering the study to provide adequate tissue.

          -  Dose Escalation Biopsy Substudy: Documented ligand 1 of programmed cell death protein
             1 (PD-L1) expression in the tumor (tumor proportion score (TPS) or combined positive
             score (CPS) > 10%).

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.

          -  Adequate organ function.

        Key Exclusion Criteria:

          -  History or evidence of clinically significant disorder, condition, or disease that, in
             the opinion of the Investigator or Medical Monitor would pose a risk to individual
             safety or interfere with the study evaluations, procedures, or completion.

          -  Dose Escalation Cohorts: History of ≥ Grade 3 Adverse Events (AEs) during prior
             treatment with an immune checkpoint inhibitor, or history of discontinuation of
             treatment with an immune checkpoint inhibitor due to AEs.

          -  Dose Expansion Cohort: Prior treatment with an immune checkpoint inhibitor (anti-PD-1,
             anti-PD-L1, or anti- ligand 2 of programmed cell death protein 1 (PD-L2) antibodies).

          -  History of autoimmune disease (for example, systemic lupus erythematosus, rheumatoid
             arthritis, inflammatory bowel disease, vascular thrombosis associated with
             antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy,
             Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis,
             or glomerulonephritis).

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) During the Dose Escalation Phase
Time Frame:Day 1 through Day 21
Safety Issue:
Description:A DLT is any toxicity defined as follows excluding toxicities clearly related to disease progression or disease-related processes occurring during the DLT assessment window (Day 1 through Day 21): Grade ≥ 4 neutropenia Grade ≥ 3 neutropenia with fever Grade ≥ 3 thrombocytopenia Grade ≥ 2 bleeding Grade ≥ 3 anemia Grade ≥ 3 or higher non-hematologic toxicity (excluding Grade 3 nausea or emesis or Grade 3 diarrhea) Grade ≥ 2 non-hematologic treatment-emergent adverse event that in the opinion of the investigator is of potential clinical significance Treatment interruption of ≥ 7 days due to unresolved toxicity Any toxicity event that precludes further administration of GS-4224 Any Grade 3 or Grade 4 elevation in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) associated with a Grade 2 elevation in bilirubin lasting ≥ 7 days An immune-related adverse event (irAE) for which immunotherapy should be permanently discontinued

Secondary Outcome Measures

Measure:Pharmacokinetic (PK) Parameter: Tlast of GS-4224 During the Dose Escalation Phase
Time Frame:Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 24 hours postdose on Cycle 1 Days 1 and 15 (each cycle is 21 days).
Safety Issue:
Description:Tlast is defined as the time (observed time point) of Clast.
Measure:PK Parameter: Tmax of GS-4224 During the Dose Escalation Phase
Time Frame:Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 24 hours postdose on Cycle 1 Days 1 and 15 (each cycle is 21 days).
Safety Issue:
Description:Tmax is defined as the time (observed time point) of Cmax.
Measure:PK Parameter: Cmax of GS-4224 During the Dose Escalation Phase
Time Frame:Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 24 hours postdose on Cycle 1 Days 1 and 15 (each cycle is 21 days).
Safety Issue:
Description:Cmax is defined as the maximum observed concentration of drug.
Measure:PK Parameter: Ctau of GS-4224 During the Dose Escalation Phase
Time Frame:Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 24 hours postdose on Cycle 1 Days 1 and 15 (each cycle is 21 days).
Safety Issue:
Description:Ctau is defined as the observed drug concentration at the end of the dosing interval.
Measure:PK Parameter: AUClast of GS-4224 During the Dose Escalation Phase
Time Frame:Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 24 hours postdose on Cycle 1 Days 1 and 15 (each cycle is 21 days).
Safety Issue:
Description:AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Measure:PK Parameter: AUCtau of GS-4224 During the Dose Escalation Phase
Time Frame:Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 24 hours postdose on Cycle 1 Days 1 and 15 (each cycle is 21 days).
Safety Issue:
Description:AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Measure:PK Parameter: t1/2 of GS-4224 During the Dose Escalation Phase
Time Frame:Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 24 hours postdose on Cycle 1 Days 1 and 15 (each cycle is 21 days).
Safety Issue:
Description:t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Measure:Percentage of Participants Experiencing ≥ Grade 3 Treatment-Emergent Adverse Events During the Dose Expansion Phase
Time Frame:First dose date through end of treatment plus 30 days, approximately 5 years
Safety Issue:
Description:
Measure:Percentage of Participants Experiencing ≥ Grade 3 Treatment-Emergent Laboratory Abnormalities During the Dose Expansion Phase
Time Frame:First dose date through end of treatment plus 30 days, approximately 5 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Gilead Sciences

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