Clinical Trials /

Study of the Safety and Effectiveness of GSK6097608 in Participants With Advanced Solid Tumors

NCT04446351

Description:

This first-time-in-human (FTIH) study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of escalating doses of GSK6097608 given as monotherapy and in combination with dostarlimab in participants with advanced solid tumors. This study will be used to define the recommended Phase 2 dose (RP2D). The study comprises 3 phases; screening phase (28 days prior to first dose), treatment phase (until disease progression, unacceptable toxicity, death, or withdrawal of consent) and follow-up phase (90 days). Approximately 100 adult participants with locally advanced, recurrent, or metastatic solid tumors will be enrolled.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of the Safety and Effectiveness of GSK6097608 in Participants With Advanced Solid Tumors
  • Official Title: A Phase 1 First-Time-in-Human, Open-Label Study of GSK6097608 Administered as Monotherapy and in Combination With Anticancer Agents in Participants With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 212214
  • NCT ID: NCT04446351

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
GSK6097608Participants receiving GSK6097608 (Arm A)
DostarlimabParticipants receiving GSK6097608 plus dostarlimab (Arm B)

Purpose

This first-time-in-human (FTIH) study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of escalating doses of GSK6097608 given as monotherapy and in combination with dostarlimab in participants with advanced solid tumors. This study will be used to define the recommended Phase 2 dose (RP2D). The study comprises 3 phases; screening phase (28 days prior to first dose), treatment phase (until disease progression, unacceptable toxicity, death, or withdrawal of consent) and follow-up phase (90 days). Approximately 100 adult participants with locally advanced, recurrent, or metastatic solid tumors will be enrolled.

Trial Arms

NameTypeDescriptionInterventions
Participants receiving GSK6097608 (Arm A)ExperimentalParticipants will be administered an IV infusion of GSK6097608 every 3 weeks as monotherapy in escalating doses.
  • GSK6097608
Participants receiving GSK6097608 plus dostarlimab (Arm B)ExperimentalParticipants will be administered an IV infusion of GSK6097608 every 3 weeks in escalating doses followed by an IV infusion of dostarlimab (every 3 weeks for 4 doses and every 6 weeks thereafter).
  • GSK6097608
  • Dostarlimab

Eligibility Criteria

        Inclusion Criteria:

          -  Adults 18 years of age or older;

          -  Female participants of childbearing potential must agree to use a highly effective
             form of contraception;

          -  Histological or cytological documentation of locally advanced, recurrent, or
             metastatic solid malignancy;

          -  Disease that has progressed after standard therapy for the specific tumor type, or for
             which standard therapy has proven to be ineffective, intolerable, or is considered
             inappropriate, or if no further standard therapy exists;

          -  Participants must provide a tumor biopsy during the screening period from a tumor
             lesion and agree to an additional on-treatment biopsy.

          -  Measurable disease per RECIST 1.1

          -  Eastern cooperative oncology group (ECOG) performance status (PS) 0 to 1

          -  Life expectancy of at least 12 weeks.

          -  Adequate organ function as determined by laboratory assessments.

          -  Adequate cardiac ejection fraction as measured by echocardiogram.

        Exclusion Criteria:

          -  Prior anti-cancer treatment including investigational agents, immune checkpoint
             inhibitors, chemotherapy, targeted therapy, and biological therapy: within 4 weeks or
             5 half-lives of the drug, whichever is shorter.

          -  Prior allogenic or autologous bone marrow transplantation or other solid organ
             transplantation.

          -  Toxicity from previous anticancer treatment, including; greater than or equal to Grade
             3 immune-mediated toxicity considered related to prior immunotherapy and that led to
             treatment discontinuation; or toxicity related to prior treatment that has not
             resolved.

          -  Known additional malignancy that progressed or required active treatment within the
             last 2 years.

          -  Uncontrolled or symptomatic central nervous system (CNS) metastases and/or
             carcinomatous meningitis.

          -  Active autoimmune disease that has required systemic disease-modifying or
             immunosuppressive treatment within the last 2 years.

          -  Concurrent medical condition requiring the use of systemic immunosuppressive
             treatment.

          -  Cirrhosis or current unstable liver or biliary disease per investigator assessment.

          -  Active infection requiring systemic treatment, known human immunodeficiency virus
             infection, or positive test for hepatitis B surface antigen (HBsAg) or hepatitis C
             virus (HCV)

          -  Prolonged QT corrected for heart rate according to Fridericia's formula as measured by
             electrocardiogram.

          -  History of hypersensitivity to monoclonal antibodies. For combination therapy, history
             of hypersensitivity to dostarlimab or its excipients.

          -  History or evidence of significant cardiovascular (CV) risk.

          -  Recent history (within 6 months) of uncontrolled symptomatic ascites or pleural
             effusions.

          -  History of idiopathic pulmonary fibrosis; interstitial lung disease; organizing
             pneumonia; noninfectious pneumonitis that required steroids, or evidence of active,
             noninfectious pneumonitis.

          -  Pregnant or lactating woman.

          -  Receipt of live vaccine within 30 days of the start of study intervention.

          -  Receipt of transfusion of blood products or administration of colony-stimulating
             factors within 14 days before the first dose of study intervention.

          -  Major surgery less than 4 weeks before the first dose of study intervention.

          -  Known drug or alcohol abuse.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with dose-limiting toxicities (DLTs)
Time Frame:Up to Day 21
Safety Issue:
Description:Number of participants with DLTs will be determined.

Secondary Outcome Measures

Measure:Number of participants with abnormal clinical chemistry values
Time Frame:Up to 2 years
Safety Issue:
Description:Number of participants with abnormal clinical chemistry parameters will be assessed.
Measure:Number of participants with abnormal hematology values
Time Frame:Up to 2 years
Safety Issue:
Description:Number of participants with abnormal hematology parameters will be assessed.
Measure:Number of participants with abnormal vital signs
Time Frame:Up to 2 years
Safety Issue:
Description:Number of participants with abnormal vital signs will be assessed.
Measure:Number of participants with abnormal urinalysis results
Time Frame:Up to 2 years
Safety Issue:
Description:Number of participants with abnormal urinalysis parameters will be assessed.
Measure:Number of participants with abnormal electrocardiogram (ECG) findings
Time Frame:Up to 2 years
Safety Issue:
Description:Number of participants with abnormal ECG parameters will be assessed.
Measure:Number of participants with dose reductions or delay
Time Frame:Up to 2 years
Safety Issue:
Description:Number of participants with dose reductions or delay will be determined.
Measure:Number of participants withdrawn due to AEs
Time Frame:Up to 2 years
Safety Issue:
Description:Number of participants withdrawn due to AEs will be determined.
Measure:Overall response rate (ORR)
Time Frame:Up to 2 years
Safety Issue:
Description:ORR is defined as percentage of participants with a confirmed partial response or better based on response evaluation criteria in solid tumors, (RECIST) 1.1
Measure:Number of participants with positive anti-drug antibodies (ADAs) against GSK6097608
Time Frame:Up to 2 years
Safety Issue:
Description:The number of participants with at least one confirmed positive ADA at any time post-Baseline will be determined.
Measure:Titers of ADAs against GSK6097608
Time Frame:Up to 2 years
Safety Issue:
Description:Titers of ADAs against GSK6097608 will be determined.
Measure:Number of participants with positive ADAs against dostarlimab
Time Frame:Up to 2 years
Safety Issue:
Description:The number of participants with at least one confirmed positive ADA at any time post-Baseline will be determined.
Measure:Titers of ADAs against dostarlimab
Time Frame:Up to 2 years
Safety Issue:
Description:Titers of ADAs against dostarlimab will be determined.
Measure:Maximum observed concentration (Cmax) for GSK6097608
Time Frame:Day 1 (Pre-dose, End of Infusion [EOI], 4 hours after EOI), Day 2 (24 hours after EOI), Day 3 to Day 4 (72 to 96 hours after EOI), Week 1, Week 2, Week 3 (pre-dose and EOI), Week 4, Week 5, Weeks 6, 9 and 12 (pre-dose and EOI)
Safety Issue:
Description:Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK6097608.
Measure:Minimum observed concentration (Cmin) for GSK6097608
Time Frame:Day 1 (Pre-dose,EOI,4 hours after EOI),Day 2 (24 hours after EOI),Day 3 to Day 4 (72 to 96 hours after EOI), Week 1,Week 2,Week 3 (pre-dose and EOI),Week 4,Week 5, Weeks 6, 9, 12 and 15 (pre-dose and EOI) and pre-dose and EOI every 12 weeks up to 2 years
Safety Issue:
Description:Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK6097608.
Measure:Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC[0-infinity]) for GSK6097608
Time Frame:Day 1 (Pre-dose, EOI, 4 hours after EOI), Day 2 (24 hours after EOI), Day 3 to Day 4 (72 to 96 hours after EOI), Week 1, Week 2, Week 3 (pre-dose and EOI), Week 4, Week 5, Weeks 6, 9 and 12 (pre-dose and EOI)
Safety Issue:
Description:Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK6097608.
Measure:Area under the plasma concentration-time curve from time zero to time (AUC[0-t]) for GSK6097608
Time Frame:Day 1 (Pre-dose, EOI, 4 hours after EOI), Day 2 (24 hours after EOI), Day 3 to Day 4 (72 to 96 hours after EOI), Week 1, Week 2, Week 3 (pre-dose and EOI), Week 4, Week 5, Weeks 6, 9 and 12 (pre-dose and EOI)
Safety Issue:
Description:Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK6097608.
Measure:Apparent terminal phase half-life (t1/2) for GSK6097608
Time Frame:Day 1 (Pre-dose, EOI, 4 hours after EOI), Day 2 (24 hours after EOI), Day 3 to Day 4 (72 to 96 hours after EOI), Week 1, Week 2, Week 3 (pre-dose and EOI), Week 4, Week 5, Weeks 6, 9 and 12 (pre-dose and EOI)
Safety Issue:
Description:Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK6097608.
Measure:Cmax for dostarlimab
Time Frame:Day 1 (Pre-dose and EOI), Day 2 (24 hours after EOI), Week 1, Week 2, Week 3 (pre-dose), Week 6 (pre-dose), Week 9 (pre-dose), and Week 12 (pre-dose)
Safety Issue:
Description:Blood samples will be collected at indicated time points for pharmacokinetic analysis of dostarlimab.
Measure:Cmin for dostarlimab
Time Frame:Day 1 (Pre-dose and EOI), Day 2 (24 hours after EOI), Week 1, Week 2, Week 3 (pre-dose), Week 6 (pre-dose), Week 9 (pre-dose), Week 12 (pre-dose), and pre-dose every 12 weeks up to 2 years
Safety Issue:
Description:Blood samples will be collected at indicated time points for pharmacokinetic analysis of dostarlimab.
Measure:AUC(0-infinity) for dostarlimab
Time Frame:Day 1 (Pre-dose and EOI), Day 2 (24 hours after EOI), Week 1, Week 2, Week 3 (pre-dose), Week 6 (pre-dose), Week 9 (pre-dose), and Week 12 (pre-dose)
Safety Issue:
Description:Blood samples will be collected at indicated time points for pharmacokinetic analysis of dostarlimab.
Measure:AUC(0-t) for dostarlimab
Time Frame:Day 1 (Pre-dose and EOI), Day 2 (24 hours after EOI), Week 1, Week 2, Week 3 (pre-dose), Week 6 (pre-dose), Week 9 (pre-dose), and Week 12 (pre-dose)
Safety Issue:
Description:Blood samples will be collected at indicated time points for pharmacokinetic analysis of dostarlimab.
Measure:t1/2 for dostarlimab
Time Frame:Day 1 (Pre-dose and EOI), Day 2 (24 hours after EOI), Week 1, Week 2, Week 3 (pre-dose), Week 6 (pre-dose), Week 9 (pre-dose), and Week 12 (pre-dose)
Safety Issue:
Description:Blood samples will be collected at indicated time points for pharmacokinetic analysis of dostarlimab.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:GlaxoSmithKline

Trial Keywords

  • GSK6097608
  • Dostarlimab
  • Dose escalation
  • Pharmacokinetics
  • Pharmacodynamics
  • Advanced solid tumors
  • First-time-in-human

Last Updated

July 15, 2020