Clinical Trials /

First-time-in-human (FTIH) Study of GSK3145095 Alone and in Combination With Other Anticancer Agents in Adults With Advanced Solid Tumors

NCT03681951

Description:

In an unbiased CRISPR screen, RIPK1 was identified as a top gene contributing to immunotherapy resistance. In addition, RIPK1 has been reported to drive pancreatic oncogenesis. In murine models, inhibition of RIPK1 kinase activity in the pancreatic tumor microenvironment leads to the replacement of tumor-permissive myeloid infiltrates with innate cells that promote an effective antitumor response by adaptive cells. The investigators hypothesize that inhibition of RIPK1 in human pancreatic cancer subjects will modulate the immune infiltrate to sensitize tumors to checkpoint blockade.

Related Conditions:
  • Breast Carcinoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: First-time-in-human (FTIH) Study of GSK3145095 Alone and in Combination With Other Anticancer Agents in Adults With Advanced Solid Tumors
  • Official Title: A Phase I/II, Open-Label Study to Investigate the Safety, Clinical Activity, Pharmacokinetics, and Pharmacodynamics of GSK3145095 Administered Alone and in Combination With Anticancer Agents Including Pembrolizumab in Adult Participants With Selected Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 205013
  • NCT ID: NCT03681951

Conditions

  • Neoplasms, Pancreatic

Interventions

DrugSynonymsArms
GSK3145095Part 1: Dose Escalation - GSK3145095 monotherapy
PembrolizumabPart 2: Dose Escalation - GSK3145095 + pembrolizumab

Purpose

In an unbiased CRISPR screen, RIPK1 was identified as a top gene contributing to immunotherapy resistance. In addition, RIPK1 has been reported to drive pancreatic oncogenesis. In murine models, inhibition of RIPK1 kinase activity in the pancreatic tumor microenvironment leads to the replacement of tumor-permissive myeloid infiltrates with innate cells that promote an effective antitumor response by adaptive cells. The investigators hypothesize that inhibition of RIPK1 in human pancreatic cancer subjects will modulate the immune infiltrate to sensitize tumors to checkpoint blockade.

Detailed Description

      Study 205013 is a Phase 1 FTIH study of GSK3145095 alone and in combination with other
      anticancer agents including pembrolizumab in subjects with pancreatic ductal adenocarcinoma
      (PDAC) and other selected tumors. The study includes up to 4 parts: Part 1 dose escalation
      will be conducted in approximately 30 adult subjects with advanced or metastatic PDAC using
      escalating doses of GSK3145095 as monotherapy only. Part 2 will combine escalating doses of
      GSK3145095 with 200 milligram (mg) pembrolizumab. Dose escalation of GSK3145095 will begin at
      least one level below the highest dose shown to have an acceptable toxicity profile in at
      least 3 subjects in Part 1. Part 2 may be conducted in a broader population of selected solid
      tumors using a combination of escalating doses of GSK3145095 and 200 mg pembrolizumab. Part 3
      will enroll subjects treated with one or more dose levels of GSK3145095 in combination with
      200 mg pembrolizumab. Part 4 will investigate the combination of additional anticancer agents
      with one or more doses of GSK3145095 identified as safe in Part 1. Up to approximately 220
      subjects will be treated in the study. Parts 1 and 2 will each treat up to approximately 30
      subjects. Parts 3 and 4 will treat up to approximately 160 subjects (up to 80 subjects in
      each Part). The total duration of the study is expected to last up to 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Part 1: Dose Escalation - GSK3145095 monotherapyExperimentalIn Part 1, advanced or metastatic PDAC will be enrolled. Part 1 will be using escalating doses of GSK3145095 (100 mg, 200 mg, 400 mg, 800 mg, and 1600 mg) orally as monotherapy only twice daily (BID) for up to 2 years. Subjects will receive a single dose of GSK3145095 on Day 1 with the BID schedule starting on Day 2.
  • GSK3145095
Part 2: Dose Escalation - GSK3145095 + pembrolizumabExperimentalIn Part 2, subjects with selected solid tumors, including but not limited to, PDAC, NSCLC, TNBC and/or melanoma will be enrolled. Part 2 will be using GSK3145095 combination escalation to start at least one dose level below the highest dose of GSK3145095 shown to be safe in Part 1, orally BID for up to 2 years along with pembrolizumab 200 mg intravenous (IV) every 3 weeks (Q3W) for up to 2 years.
  • GSK3145095
  • Pembrolizumab
Part 3: Dose Expansion - GSK3145095 + pembrolizumabExperimentalIn Part 3, subjects with selected solid tumors will be enrolled. Part 3 will be using GSK3145095 at one or two dose levels shown to be tolerable in Part 2 orally BID for up to 2 years along with pembrolizumab 200 mg IV Q3W for up to 2 years.
  • GSK3145095
  • Pembrolizumab
Part 4: Dose Expansion - GSK3145095 + anticancer agentExperimentalIn Part 4, subjects with selected solid tumors will be enrolled. Part 4 will be using GSK3145095 at one or two dose levels shown to be tolerable in Part 2 orally BID for up to 2 years along with combination of additional anticancer agents.
  • GSK3145095

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects must provide signed, written informed consent.

          -  Male and female subjects, age >=18 years (at the time consent is obtained). a) Male
             subjects are eligible to participate if they agree to the following during the study
             treatment period and for at least 15 days (Part 1) and 120 days (Parts 2-4) after the
             last dose of study treatment: Refrain from donating sperm, be abstinent from
             heterosexual or homosexual intercourse as their preferred and usual lifestyle
             (abstinent on a long term and persistent basis) and agree to remain abstinent or must
             agree to use contraception/barrier: male condom and female partner to use an
             additional highly effective contraceptive method with a failure rate of <1 percent per
             year. b) female subjects are eligible to participate if they are not either pregnant
             or breastfeeding, and at least one of the following conditions applies: is not a woman
             of childbearing potential (WOCBP), is a WOCBP and using a contraceptive method that is
             highly effective (with a failure rate of <1 percent per year), with low user
             dependency during the study treatment period and for at least 15 days (Part 1) and 120
             days (Parts 2-4) after the last dose of study treatment and agrees not to donate eggs
             (ova, oocytes) for the purpose of reproduction during this period. The investigator
             should evaluate the effectiveness of the contraceptive method in relationship to the
             first dose of study treatment. Hormonal contraception may be susceptible to
             interaction with the study drug, which may reduce the efficacy of the contraceptive
             method. Therefore, a barrier method is also required for subjects using a hormonal
             option (including hormonal intrauterine device [IUD], oral contraceptive pills/ patch/
             vaginal inserts, and hormonal implants) and both highly effective methods of
             contraception should be utilized during the treatment period and for at least 15 days
             (Part 1) and 120 days (Parts 2-4) after the last dose of study treatment.If a highly
             effective non-hormonal method is used, then only one method of contraception is
             required (by a female participant or partner of a male participant; in either
             situation the male partner must still use a male condom in addition) during the
             treatment period and for at least 15 days (Part 1) and 120 days (Parts 2-4) after the
             last dose of study treatment. A WOCBP must have a negative highly sensitive pregnancy
             test (urine or serum) as required by local regulations) within 24 hours before the
             first dose of study intervention. If a urine test cannot be confirmed as negative
             (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the
             subject must be excluded from participation if the serum pregnancy result is positive.
             If the subject hasn't been on an acceptable method of contraception for at least 2
             weeks prior to start of therapy, pregnancy testing must be done weekly for the first
             month of treatment. Additional requirements for pregnancy testing during and after
             study treatment. The investigator is responsible for review of medical history,
             menstrual history, and recent sexual activity to decrease the risk for inclusion of a
             woman with an early undetected pregnancy.

          -  Histological documentation of locally advanced, recurrent or PDAC (Part 1), non-small
             cell lung cancer (NSCLC), triple negative breast cancer (TNBC), or melanoma (Part 2)
             that has progressed after standard therapy appropriate for the specific tumor type, or
             for which standard therapy has proven to be ineffective, intolerable, or is considered
             inappropriate. Subjects should have received at least one, but not more than 2 prior
             lines of therapy for advanced disease including both standards of care and
             investigational therapies. Subjects whose cancers harbor molecular alterations for
             which targeted therapy is standard of care should have received health
             authority-approved appropriate targeted therapy for their tumor types before
             enrollment.

          -  All subjects in Parts 1 and 2 must consent to provide a fresh biopsy during screening
             of a primary tumor lesion or from other metastases (e.g. liver, lung, etc.), and a
             second biopsy after approximately 5 weeks of treatment.

          -  Measurable disease per RECIST version 1.1. Palpable lesions that are not measurable by
             radiologic or photographic evaluations may not be utilized as the only measurable
             lesion. Subjects are encouraged to provide a pre-Baseline scan (within 24 weeks before
             the Baseline scan) to support exploratory investigation of tumor growth kinetics.

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1.

          -  Life expectancy of at least 12 weeks.

          -  Adequate organ function.

          -  QT duration corrected for heart rate by Fridericia's formula (QTcF) <450 milliseconds
             (or QTcF <480 milliseconds for subjects with bundle branch block).

        Exclusion Criteria:

          -  Prior treatment with the following agents: Agents affecting tumor associated
             macrophage function or number, including but not limited to inhibitors of
             Receptor-interacting protein 1 (RIP1), Receptor-interacting protein 3 (RIP3), Colony
             stimulating factor 1 receptor (CSFR-1), C-C chemokine receptor type 2 (CCR2), and
             Cluster of differentiation 40 (CD40). Other anticancer therapy, including
             chemotherapy, targeted therapy, and biological therapy, within 14 days or 5 half-lives
             (from last dose of prior treatment to first dose of GSK3145095), whichever is shorter.
             Prior radiation therapy is permissible if at least one non-irradiated measurable
             lesion is available for assessment via RECIST version 1.1. No washout after palliative
             radiation is required. Investigational therapy within 14 days or 5 half-lives (from
             last dose of prior treatment to first dose of GSK3145095), whichever is shorter.

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

          -  Toxicity from previous treatment: Subjects whose toxicity related to prior treatment
             has not resolved to <=Grade 1 (except alopecia, hearing loss, Grade <=2 neuropathy or
             endocrinopathy managed with replacement therapy) are not eligible.

          -  Malignancy other than disease under study, except as noted: Subject with any other
             malignancy from which the subject has been disease-free for more than 2 years and, in
             the opinion of the principal investigators and GlaxoSmithKline (GSK) Medical Monitor,
             will not affect the evaluation of the effects of this clinical trial treatment on
             currently targeted malignancy, can be included in this clinical trial.

          -  Major surgery <=4 weeks before the first dose of study treatment. Subjects must have
             also fully recovered from any surgery (major or minor) and/or its complications before
             initiating study treatment.

          -  Active autoimmune disease that has required systemic treatment within the last 2 years
             (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive
             drugs). Replacement therapy (e.g., thyroxine or physiologic corticosteroid replacement
             therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of
             systemic treatment.

          -  Concurrent medical condition requiring the use of systemic immunosuppressive
             medications within 28 days before the first dose of study treatment. Physiologic doses
             of corticosteroids for treatment of endocrinopathies or steroids with minimal systemic
             absorption, including topical, inhaled, or intranasal corticosteroids, may be
             continued if the subject is on a stable dose.

          -  Active infection (including active herpes zoster infection), known human
             immunodeficiency virus infection, or positive test for hepatitis B surface antigen or
             hepatitis C.

          -  Current active liver or biliary disease (except for Gilbert's syndrome or asymptomatic
             gallstones, liver metastases, or otherwise stable chronic liver disease per
             investigator assessment).

          -  Known current drug or alcohol abuse.

          -  Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel
             disease, intra-abdominal abscess, or gastrointestinal obstruction.

          -  Receipt of any live vaccine within 4 weeks before starting study treatment.

          -  Recent history of allergen desensitization therapy within 4 weeks before starting
             study treatment (applies to subjects enrolled in Parts 2 and 3 only).

          -  History or evidence of cardiovascular risk including any of the following: recent
             (within the past 6 months) history of serious uncontrolled cardiac arrhythmia or
             clinically significant electrocardiogram (ECG) abnormalities including second degree
             (Type II) or third degree atrioventricular block. Documented cardiomyopathy,
             myocardial infarction, acute coronary syndromes (including unstable angina pectoris),
             coronary angioplasty, stenting, or bypass grafting within the past 6 months before
             beginning screening. Documented congestive heart failure (Class II, III, or IV) as
             defined by the New York Heart Association functional classification system. Recent
             (within the past 6 months) history of symptomatic pericarditis.

          -  Current or history of idiopathic pulmonary fibrosis, interstitial lung disease, or
             organizing pneumonia.

          -  History of (non-infectious) pneumonitis that required steroids or current pneumonitis.

          -  Recent history (within 14 days) of ascites or pleural effusions requiring drainage.

          -  Any serious and/or unstable pre-existing medical, psychiatric disorder, or other
             condition that could interfere with the subjects safety, obtaining informed consent,
             or compliance to the study procedures.

          -  Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or
             child) who is investigational site or sponsor staff directly involved with this trial,
             unless prospective Institutional Review Board (IRB) approval (by chair or designee) is
             given allowing exception to this criterion for a specific subject.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of subjects with adverse events (AEs) and serious adverse events (SAEs)-Part 1
Time Frame:Up to 2 years
Safety Issue:
Description:An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAEs are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.

Secondary Outcome Measures

Measure:Overall response rate (ORR) based on RECIST 1.1 criteria-Part 1
Time Frame:Up to 2 years
Safety Issue:
Description:ORR is defined as the percentage of subjects with tumor size reduction of a predefined amount and for a minimum time period. Response duration usually is measured from the time of initial response until documented tumor progression. ORR will be evaluated according to RECIST 1.1.
Measure:ORR based on RECIST 1.1 criteria-Part 2
Time Frame:Up to 2 years
Safety Issue:
Description:ORR is defined as the percentage of subjects with tumor size reduction of a predefined amount and for a minimum time period. Response duration usually is measured from the time of initial response until documented tumor progression. will be evaluated according to RECIST 1.1.
Measure:Number of subjects with progression-free survival (PFS)-Part 3
Time Frame:Up to 2 years
Safety Issue:
Description:PFS is defined as time from the date of first dose to the date of disease progression according to clinical or radiological assessment or death due to any causes, whichever occurs earliest.
Measure:Number of subjects with PFS-Part 4
Time Frame:Up to 2 years
Safety Issue:
Description:PFS is defined as time from the date of first dose to the date of disease progression according to clinical or radiological assessment or death due to any causes, whichever occurs earliest.
Measure:Number of subjects with overall survival -Part 3
Time Frame:Up to 2 years
Safety Issue:
Description:Overall survival is defined as time from the date of first dose to the date of death due to any cause.
Measure:Number of subjects with overall survival -Part 4
Time Frame:Up to 2 years
Safety Issue:
Description:Overall survival is defined as time from the date of first dose to the date of death due to any cause.
Measure:Number of subjects with AEs and SAEs-Part 3
Time Frame:Up to 2 years
Safety Issue:
Description:An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAEs are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Measure:Number of subjects with AEs and SAEs-Part 4
Time Frame:Up to 2 years
Safety Issue:
Description:An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAEs are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Measure:Number of subjects with AEs and SAEs defined by severity-Part 3
Time Frame:Up to 2 years
Safety Issue:
Description:AE and SAE classified as per severity mild, moderate and severe will be presented.
Measure:Number of subjects with AEs and SAEs defined by severity-Part 4
Time Frame:Up to 2 years
Safety Issue:
Description:AE and SAE classified as per severity mild, moderate and severe will be presented.
Measure:Area under the plasma drug concentration versus time curve (AUC [0-t]) following single dose of GSK3145095-Part 1
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of AUC (0-t) following single dose of GSK3145095.
Measure:(AUC 0-t) following single dose of GSK3145095-Part 2
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of AUC (0-t) following single dose of GSK3145095.
Measure:Area under the concentration-time curve over the dosing interval (AUC [0-tau]) following single dose of GSK3145095-Part 1
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of AUC (0-tau) following single dose of GSK3145095.
Measure:AUC (0-tau) following single dose of GSK3145095-Part 2
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of AUC (0-tau) following single dose of GSK3145095.
Measure:Maximum observed plasma drug concentration (Cmax) following single dose of GSK3145095-Part 1
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of Cmax following single dose of GSK3145095.
Measure:Cmax following single dose of GSK3145095-Part 2
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of Cmax following single dose of GSK3145095.
Measure:Minimum observed plasma drug concentration (Cmin) following single dose of GSK3145095-Part 1
Time Frame:Day 1:24 hours post-dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of Cmin following single dose of GSK3145095.
Measure:Cmin following single dose of GSK3145095-Part 2
Time Frame:Day 1:24 hours post-dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of Cmin following single dose of GSK3145095.
Measure:Time to maximum observed plasma drug concentration (tmax) following single dose of GSK3145095-Part 1
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of tmax following single dose of GSK3145095.
Measure:tmax following single dose of GSK3145095-Part 2
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of tmax following single dose of GSK3145095.
Measure:Clearance (CL/F) following single dose of GSK3145095-Part 1
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of CL/F following single dose of GSK3145095.
Measure:CL/F following single dose of GSK3145095-Part 2
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of CL/F following single dose of GSK3145095.
Measure:Volume of distribution (V/F) following single dose of GSK3145095-Part 1
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of V/F following single dose of GSK3145095.
Measure:V/F following single dose of GSK3145095-Part 2
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of V/F following single dose of GSK3145095.
Measure:Terminal half-life (t1/2) following single dose of GSK3145095-Part 1
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of t1/2 following single dose of GSK3145095.
Measure:t1/2 following single dose of GSK3145095-Part 2
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of t1/2 following single dose of GSK3145095.
Measure:AUC (0-t) following repeat dose of GSK3145095-Part 1
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of AUC (0-t) following repeat dose of GSK3145095.
Measure:AUC (0-t) following repeat dose of GSK3145095-Part 2
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of AUC (0-t) following repeat dose of GSK3145095.
Measure:AUC (0-tau) following repeat dose of GSK3145095-Part 1
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of AUC (0-tau) following repeat dose of GSK3145095.
Measure:AUC (0-tau) following repeat dose of GSK3145095-Part 2
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of AUC (0-tau) following repeat dose of GSK3145095.
Measure:Cmax following repeat dose of GSK3145095-Part 1
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of Cmax following repeat dose of GSK3145095.
Measure:Cmax following repeat dose of GSK3145095-Part 2
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of Cmax following repeat dose of GSK3145095.
Measure:Cmin following repeat dose of GSK3145095-Part 1
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of Cmin following repeat dose of GSK3145095.
Measure:Cmin following repeat dose of GSK3145095-Part 2
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of Cmin following repeat dose of GSK3145095.
Measure:tmax following repeat dose of GSK3145095-Part 1
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of tmax following repeat dose of GSK3145095.
Measure:tmax following repeat dose of GSK3145095-Part 2
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of tmax following repeat dose of GSK3145095.
Measure:CL/F following repeat dose of GSK3145095-Part 1
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of CL/F following repeat dose of GSK3145095.
Measure:CL/F following repeat dose of GSK3145095-Part 2
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of CL/F following repeat dose of GSK3145095.
Measure:V/F following repeat dose of GSK3145095-Part 1
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of V/F following repeat dose of GSK3145095.
Measure:V/F following repeat dose of GSK3145095-Part 2
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of V/F following repeat dose of GSK3145095.
Measure:t1/2 following repeat dose of GSK3145095-Part 1
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of t1/2 following repeat dose of GSK3145095.
Measure:t1/2 following repeat dose of GSK3145095-Part 2
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of t1/2 following repeat dose of GSK3145095.
Measure:Dose proportionality using AUC following single dose of GSK3145095-Part 1
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Dose proportionality will be evaluated for GSK3145095.
Measure:Dose proportionality using Cmax following single dose of GSK3145095-Part 1
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Dose proportionality will be evaluated for GSK3145095.
Measure:Dose proportionality using AUC following repeat dose of GSK3145095-Part 1
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Dose proportionality will be evaluated for GSK3145095.
Measure:Dose proportionality using Cmax following repeat dose of GSK3145095-Part 1
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Dose proportionality will be evaluated for GSK3145095.
Measure:Dose proportionality using AUC (0-tau) following single dose of GSK3145095-Part 2
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Dose proportionality will be evaluated for GSK3145095.
Measure:Dose proportionality using Cmax following single dose of GSK3145095-Part 2
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Dose proportionality will be evaluated for GSK3145095.
Measure:Dose proportionality using AUC (0-tau) following repeat dose of GSK3145095-Part 2
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Dose proportionality will be evaluated for GSK3145095.
Measure:Dose proportionality using Cmax following repeat dose of GSK3145095-Part 2
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Dose proportionality will be evaluated for GSK3145095.
Measure:Accumulation ratio following repeat dose of GSK3145095-Part 1
Time Frame:Days 1: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour; Days 15: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Accumulation ratio will be calculated as AUC(0-tau) at Day 15 divided by AUC(0-tau) at Day 1 for GSK3145095.
Measure:Accumulation ratio following repeat dose of GSK3145095-Part 2
Time Frame:Days 1: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour; Days 15: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Accumulation ratio will be calculated as AUC(0-tau) at Day 15 divided by AUC(0-tau) at Day 1 for GSK3145095.
Measure:Time invariance following repeat dose of GSK3145095-Part 1
Time Frame:Days 1: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour; Days 15: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Time invariance will be calculated as calculated as AUC(0-tau) at Day 15 divided by AUC(0-infinity) at Day 1 for GSK3145095.
Measure:Time invariance following repeat dose of GSK3145095 of GSK3145095-Part 2
Time Frame:Days 1: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour; Days 15: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Time invariance will be calculated as calculated as AUC(0-tau) at Day 15 divided by AUC(0-infinity) at Day 1 for GSK3145095.
Measure:Plasma concentration of pembrolizumab -Part 2
Time Frame:Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years
Safety Issue:
Description:Blood samples will be collected at indicated time points for the determination of plasma concentration of pembrolizumab.
Measure:Cmax of pembrolizumab-Part 2
Time Frame:Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of Cmax following pembrolizumab.
Measure:AUC (0-tau) of pembrolizumab-Part 2
Time Frame:Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22 (pre-dose)
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of AUC (0-tau) following pembrolizumab.
Measure:Cmin of pembrolizumab-Part 2
Time Frame:Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of Cmin following pembrolizumab.
Measure:AUC (0-t) following single dose of GSK3145095-Part 3
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of AUC (0-t) following single dose of GSK3145095.
Measure:Cmax following single dose of GSK3145095-Part 3
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of Cmax following single dose of GSK3145095.
Measure:tmax following single dose of GSK3145095-Part 3
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of tmax following single dose of GSK3145095.
Measure:t1/2 following single dose of GSK3145095-Part 3
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of t1/2 following single dose of GSK3145095.
Measure:AUC (0-t) following repeat dose of GSK3145095-Part 3
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of AUC(0-t) following repeat dose of GSK3145095.
Measure:Cmax following repeat dose of GSK3145095-Part 3
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of Cmax following repeat dose of GSK3145095.
Measure:tmax following repeat dose of GSK3145095-Part 3
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of tmax following repeat dose of GSK3145095.
Measure:t1/2 following repeat dose of GSK3145095-Part 3
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of t1/2 following repeat dose of GSK3145095.
Measure:AUC (0-t) following single dose of pembrolizumab-Part 3
Time Frame:Study Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hour after end of infusion
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of AUC(0-t) following single dose of pembrolizumab.
Measure:AUC (0-tau) following single dose of pembrolizumab -Part 3
Time Frame:Study Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hour after end of infusion
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of AUC(0-tau) following single dose of pembrolizumab.
Measure:Cmax following single dose of pembrolizumab -Part 3
Time Frame:Study Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hour after end of infusion
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of Cmax following single dose of pembrolizumab.
Measure:tmax following single dose of pembrolizumab -Part 3
Time Frame:Study Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hour after end of infusion
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of tmax following single dose of pembrolizumab.
Measure:t1/2 following single dose of pembrolizumab -Part 3
Time Frame:Study Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hour after end of infusion
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of t1/2 following single dose of pembrolizumab.
Measure:AUC (0-t) following repeat dose of pembrolizumab -Part 3
Time Frame:Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of AUC(0-t) following repeat dose of pembrolizumab.
Measure:AUC (0-tau) following repeat dose of pembrolizumab -Part 3
Time Frame:Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of AUC(0-tau) following repeat dose of pembrolizumab.
Measure:Cmax following repeat dose of pembrolizumab -Part 3
Time Frame:Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of Cmax following repeat dose of pembrolizumab.
Measure:tmax following repeat dose of pembrolizumab -Part 3
Time Frame:Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of tmax following repeat dose of pembrolizumab.
Measure:t1/2 following repeat dose of pembrolizumab -Part 3
Time Frame:Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years
Safety Issue:
Description:Blood samples will be collected at the indicated time points for the determination of t1/2 following repeat dose of pembrolizumab.
Measure:Dose proportionality using AUC following single dose of GSK3145095-Part 3
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Dose proportionality will be evaluated for GSK3145095.
Measure:Dose proportionality using Cmax following single dose of GSK3145095-Part 3
Time Frame:Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours
Safety Issue:
Description:Dose proportionality will be evaluated for GSK3145095.
Measure:Dose proportionality using AUC (0-tau) following repeat dose of GSK3145095-Part 3
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Dose proportionality will be evaluated for GSK3145095.
Measure:Dose proportionality using Cmax following repeat dose of GSK3145095-Part 3
Time Frame:Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Dose proportionality will be evaluated for GSK3145095.
Measure:Accumulation ratio following repeat dose of GSK3145095-Part 3
Time Frame:Days 1: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour; Days 15: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Accumulation ratio will be calculated as AUC(0-tau) at Day 15 divided by AUC(0-tau) at Day 1 for GSK3145095.
Measure:Time invariance following repeat dose of GSK3145095-Part 3
Time Frame:Days 1: Pre - dose ,0.5,1,1.5,2,3,4,6,8,10,24 hour; Days 15: Pre - dose ,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose ; Day 15:0.5,1,2,3,6,8 hour post evening dose
Safety Issue:
Description:Time invariance will be calculated as calculated as AUC(0-tau) at Day 15 divided by AUC(0-infinity) at Day 1 for GSK3145095.
Measure:Dose proportionality using AUC following single dose of pembrolizumab-Part 3
Time Frame:Study Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hour after end of infusion
Safety Issue:
Description:Dose proportionality will be evaluated for pembrolizumab.
Measure:Dose proportionality using Cmax following single dose of pembrolizumab-Part 3
Time Frame:Study Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hour after end of infusion
Safety Issue:
Description:Dose proportionality will be evaluated for pembrolizumab.
Measure:Dose proportionality using AUC (0-tau) following repeat dose of pembrolizumab-Part 3
Time Frame:Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years.
Safety Issue:
Description:Dose proportionality will be evaluated for pembrolizumab.
Measure:Dose proportionality using Cmax following repeat dose of pembrolizumab-Part 3
Time Frame:Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years.
Safety Issue:
Description:Dose proportionality will be evaluated for pembrolizumab.
Measure:Accumulation ratio following repeat dose of pembrolizumab-Part 3
Time Frame:Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years
Safety Issue:
Description:Accumulation ratio will be calculated as AUC(0-tau) at Day 15 divided by AUC(0-tau) at Day 1 for pembrolizumab.
Measure:Time invariance following repeat dose of pembrolizumab-Part 3
Time Frame:Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years
Safety Issue:
Description:Time invariance will be calculated as calculated as AUC(0-tau) at Day 15 divided by AUC(0-infinity) at Day 1 for pembrolizumab.

Details

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

Trial Keywords

  • Anticancer Agents
  • FTIH
  • Pembrolizumab
  • Rip1K
  • GSK3145095
  • Dose Escalation
  • Immunotherapy resistance
  • Dose Expansion
  • RECIST 1.1
  • Advanced solid tumors
  • Innate immunity

Last Updated