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First Time in Humans (FTIH) Study of GSK3368715 in Subjects With Solid Tumors and Diffuse Large B-cell Lymphoma (DLBCL)

NCT03666988

Description:

Arginine methylation mediated by protein arginine methyl-transferases (PRMTs) is an important post-translational modification of proteins involved in a diverse range of cellular processes. Misregulation and overexpression of PRMT1 (a type I PRMT) has been associated with a number of solid and hematopoietic cancers. GSK3368715 leads to inhibition of tumor cell growth across tumor types with cytotoxic response observed in lymphoma, acute myeloid leukemia (AML) and a subset of solid tumor cell lines. This study will assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of GSK33368715 in subjects with relapsed/refractory DLBCL and selected solid tumors with frequent methyl-thioadenosine phosphorylase (MTAP)-deficiency. The study will consist of two parts. In Part 1 (Dose Escalation) escalating doses of GSK3368715 will be evaluated and recommended phase 2 dose (RP2D) will be established in subjects with selected solid relapsed/refractory tumors. In Part 2 (Dose Expansion), this RP2D will be further investigated in two expansion cohorts; subjects with DLBCL (Expansion Cohort 2A) and relapsed/refractory solid tumors including pancreatic, bladder, and non-small cell lung cancer (NSCLC)(Expansion Cohort 2B). The study includes a screening period, an intervention period and follow up. Approximately 40 subjects will be enrolled in Part 1 and 141 will be enrolled in Part 2.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Adenocarcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: First Time in Humans (FTIH) Study of GSK3368715 in Subjects With Solid Tumors and Diffuse Large B-cell Lymphoma (DLBCL)
  • Official Title: A Phase I, Open-label, Dose-escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK3368715 in Participants With Solid Tumors and DLBCL

Clinical Trial IDs

  • ORG STUDY ID: 207675
  • SECONDARY ID: 2018-001629-20
  • NCT ID: NCT03666988

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
GSK3368715Part 2:GSK3368715 dose expansion cohort - solid tumor subjects

Purpose

Arginine methylation mediated by protein arginine methyl-transferases (PRMTs) is an important post-translational modification of proteins involved in a diverse range of cellular processes. Misregulation and overexpression of PRMT1 (a type I PRMT) has been associated with a number of solid and hematopoietic cancers. GSK3368715 leads to inhibition of tumor cell growth across tumor types with cytotoxic response observed in lymphoma, acute myeloid leukemia (AML) and a subset of solid tumor cell lines. This study will assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of GSK33368715 in subjects with relapsed/refractory DLBCL and selected solid tumors with frequent methyl-thioadenosine phosphorylase (MTAP)-deficiency. The study will consist of two parts. In Part 1 (Dose Escalation) escalating doses of GSK3368715 will be evaluated and recommended phase 2 dose (RP2D) will be established in subjects with selected solid relapsed/refractory tumors. In Part 2 (Dose Expansion), this RP2D will be further investigated in two expansion cohorts; subjects with DLBCL (Expansion Cohort 2A) and relapsed/refractory solid tumors including pancreatic, bladder, and non-small cell lung cancer (NSCLC)(Expansion Cohort 2B). The study includes a screening period, an intervention period and follow up. Approximately 40 subjects will be enrolled in Part 1 and 141 will be enrolled in Part 2.

Trial Arms

NameTypeDescriptionInterventions
Part 1: GSK3368715 dose escalation cohortExperimentalEligible subjects with solid relapsed/refractory tumors will receive escalating doses of GSK3368715 at a starting dose of 50 mg, administered orally once daily.
  • GSK3368715
Part 1: GSK3368715 PK/PD/Metabolite/Biomarker cohortExperimentalAdditional subjects in Part 1, treated at or close to the expected the maximum tolerated dose (MTD)/RP2D, will be evaluated for metabolic and biomarker profiling. Subjects may be enrolled into this cohort(s) even after MTD/RP2D has been identified and Part 2 has been initiated.
  • GSK3368715
Part 2:GSK3368715 dose expansion cohort - DLBCL subjectsExperimentalEligible subjects with relapsed/refractory DLBCL will receive RP2D of GSK3368715 established during Part 1, administered orally once daily.
  • GSK3368715
Part 2:GSK3368715 dose expansion cohort - solid tumor subjectsExperimentalEligible subjects with relapsed/refractory solid tumors (pancreas cancer, NSCLC, and bladder cancer) will receive RP2D of GSK3368715 established during Part 1, administered orally once daily.
  • GSK3368715

Eligibility Criteria

        Inclusion Criteria:

          -  Subject must be >=18 to years of age inclusive, at the time of signing the informed
             consent.

          -  Diagnosis of one of the following; Part 1 (Dose Escalation): Histologically- or
             cytological-confirmed diagnosis of solid tumor malignancy that is metastatic or
             non-resectable; have received all standard treatment options or are no longer eligible
             for additional standard treatment options. Evaluable disease that may be measured
             directly by the size of the tumor or can be evaluated by other methods. Part 2 (Dose
             Expansion): Cohort 2A & 2B: The availability of archival tumor tissue, or willingness
             to undergo a fresh biopsy to determine MTAP status. Local MTAP or Cyclin Dependent
             Kinase Inhibitor 2A (CDKN2A) results are acceptable for enrolment, but must be
             confirmed through central laboratory testing. . Cohort 2A: Histologically- or
             cytological-confirmed diagnosis of DLBCL; relapse or refractory disease after at least
             1 but not more than 4 lines of prior therapy; at least 1 measurable site of disease
             according to the Lugano Classification. The site of disease must be greater than 1.5
             centimeter (cm) in the long axis regardless of short axis measurement or greater than
             1.0 cm in the short axis regardless of long axis measurement, and clearly measurable
             in 2 perpendicular dimensions. Cohort 2B: Pancreatic Cancer: Histologically or
             cytologically confirmed adenocarcinoma of the pancreas; unresectable, locally advanced
             (Stage III), or metastatic (Stage IV) disease; relapsed or refractory disease after at
             least 1 prior line of approved, systemic therapy; at least 1 measurable tumor lesion
             per RECIST 1.1. NSCLC: histologically or cytologically confirmed NSCLC; stage IV
             disease; tested for presence of echinoderm microtubule-associated protein-like 4-
             anaplastic lymphoma kinase (EML4-ALK) rearrangement; received at least 2 prior lines
             of approved, systemic therapy, of which 1 therapy has to be a platinum containing
             regimen or failed a first-line platinum-containing regimen in combination with an
             anti- progressive disease (PD1) monocloncal antibody and refused a second-line regimen
             despite being informed about the different therapeutic options and their specific
             clinical benefit by the investigator; the content of this informed consent discussion
             including the therapeutic options reviewed by the investigator need to be documented
             and the subject needs to sign a specific consent form; at least 1 measurable tumor
             lesion per RECIST 1.1. Transitional cell carcinoma of the Urothelium: histologically
             or cytologically confirmed transitional cell carcinoma (TCC) of the urothelium
             (urinary bladder, urethra, ureter or renal pelvis) including mixed pathology with
             predominantly (that is [i.e.], > 50 percent of the histopathology sample) TCC with the
             exception of neuroendocrine or small cell carcinoma; unresectable, locally advanced
             (T4b) or metastatic (lymph node or visceral) disease; relapsed or refractory disease
             after at least 1 prior line of approved systemic therapy; at least 1 measurable tumor
             lesion per RECIST 1.1.

          -  Adequate organ function as defined by: Absolute neutrophil count (ANC) with a
             laboratory value of >=1.5 times 10^9 per liter (L); Hemoglobin with a laboratory value
             of >=9 grams per deciliter (g/dL) for solid malignancy and >=8 g/dL for Non-Hodgkin's
             lymphoma; Platelets with a laboratory value of >=100 times 10^9/ L; prothrombin time/
             International Normalization Ratio (PT/INR) and partial thromboplastin time (PTT) with
             a laboratory value of <=1.5 times upper limit of normal (ULN), unless subject is
             receiving systemic anticoagulation (Hematologic); Albumin with a laboratory value of
             >=2 g/dL, total bilirubin with a laboratory value of <=1.5 times ULN, alanine
             aminotransferase (ALT) with a laboratory value of <=2.5 times ULN or <5 times ULN is
             acceptable for subjects with documented liver metastases/tumor infiltration (Hepatic);
             calculated creatinine clearance by Chronic Kidney Disease Epidemiology Collaboration
             (CKD-EPI) equation or measured from 24 h urine with a laboratory value of >= 50
             milliliters per min (mL/min) (Renal); Ejection fraction with a laboratory value of
             >=Lower limit of normal (LLN) by echocardiogram (minimum of 50 percent)/ multigated
             (radionuclide) angiogram (MUGA), Electrocardiogram (ECG): corrected QT (QTc) interval
             using Fridericia's formula (QTcF) with a laboratory value of <450 milliseconds (msec)
             (Cardiac).

          -  Eastern cooperative oncology group (ECOG) performance status of 0 or 1.

          -  Able to swallow and retain orally-administered medication.

          -  Availability of a biopsy of the tumor tissue obtained at any time from the initial
             diagnosis to study entry.

          -  A female subject is eligible to participate if she is not pregnant or breastfeeding,
             and at least one of the following conditions applies; is not a woman of childbearing
             potential (WOCBP) or is a WOCBP and using a contraceptive method that is highly
             effective, with a failure rate of <1 percent, during the intervention period and for
             at least 120 days, corresponding to the time needed to eliminate any study
             intervention(s) (example given [e.g.], 5 terminal half-lives) after the last dose of
             study intervention. The investigator should evaluate the effectiveness of the
             contraceptive method in relationship to the first dose of study intervention. A WOCBP
             must have a negative highly sensitive pregnancy test (urine as required by local
             regulations) within 7 days before the first dose of study intervention. 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. Male subjects are eligible to participate if they agree to the
             following during the intervention period and for at least 100 days, corresponding to
             time needed to eliminate study intervention(s) (e.g., 5 terminal half-lives) plus 90
             days after the last dose of study intervention: Refrain from donating sperm plus
             either: 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 as detailed below; agree
             to use a male condom and should also be advised of the benefit for a female partner to
             use a highly effective method of contraception as a condom may break or leak when
             having sexual intercourse with a woman of childbearing potential who is not currently
             pregnant; agree to use male condom when engaging in any activity that allows for
             passage of ejaculate to another person.

          -  Capable of giving signed informed consent.

        Exclusion Criteria:

          -  History of malignancy other than the disease under study. Subjects who have been
             disease-free for 5 years, or subjects with a history of completely resected
             non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
             Subjects with second malignancies that are indolent or definitively treated may be
             enrolled even if less than 5 years have elapsed since treatment.

          -  Primary central nervous system (CNS) tumors, Glioblastoma multiforme (GBM),
             symptomatic or untreated leptomeningeal or brain metastases or spinal cord
             compression. Subjects previously treated for these conditions that have had stable CNS
             disease (verified with consecutive imaging studies) for >1 months, are asymptomatic
             and off corticosteroids, or are on stable dose of corticosteroids for at least 1 month
             prior to study Day 1 are permitted. Stability of brain metastases must be confirmed
             with imaging. Subjects treated with gamma knife therapy can be enrolled 2 weeks
             post-procedure as long as there are no post-procedure complications/they are stable.

          -  Any severe or uncontrolled systemic diseases (e.g., unstable or uncompensated
             respiratory, hepatic, renal, cardiac disease, or clinically significant bleeding
             episodes, or active infection).

          -  Any serious and/or unstable pre-existing medical, psychiatric disorder, or other
             conditions that could interfere with subject's safety, obtaining informed consent or
             compliance to the study procedures, in the opinion of the Investigator.

          -  Any clinically significant gastrointestinal (GI) abnormalities that may alter
             absorption such as malabsorption syndrome or major resection of the stomach and/or
             bowels.

          -  History of known human immunodeficiency virus (HIV) infection or positive HIV test
             result at screening.

          -  Presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test
             result at screening to first dose of study intervention.

          -  Any of the following cardiac abnormalities: Uncontrolled high blood pressure; any
             history of coronary artery disease, including acute coronary syndromes, myocardial
             infarction, unstable angina, and history of coronary angioplasty, or stenting;
             presence of a cardiac pacemaker or implanted defibrillator; atrioventricular
             (AV)-block (including 1st degree AV block if PR >250 msec, and other more advanced
             forms of AV block), right bundle branch block (RBBB), left bundle branch block (LBBB),
             and any fasicular hemiblocks; A QRS interval at Screening or Baseline >100 msec;
             subjects with any symptomatic or sustained arrhythmias (past or present), including
             but not limited to: Atrial fibrillation, Atrial flutter, Ventricular tachycardia,
             Ventricular fibrillation, Supraventricular tachycardia; Current or past congestive
             heart failure; Evidence of a left ventricular ejection fraction below the
             institutional lower limit of normal on Screening echocardiogram; Evidence of
             significant structural heart disease on echocardiography at Screening (including any
             valvular disease greater than "mild" in severity); Cardiac troponin > upper limit of
             the reference range at Screening.

          -  Treatment with any local or systemic anti-neoplastic therapy or investigational
             anticancer agent within 14 days or 4 half-lives, whichever is longer, up to a maximum
             wash-out period of 28 days prior to initiation of study drug administration.
             Anti-androgen therapies for prostate cancer, such as bicalutamide, must be stopped 28
             days prior to first dose of GSK3368715. Second-line hormone therapies such as
             enzalutamide or abiraterone should be stopped 14 days prior to enrolment. Subjects
             with prostate cancer may remain on luteinizing hormone-releasing hormone (LHRH)
             agonists or antagonists and/or low-dose prednisone or prednisolone (up to 10
             milligrams per day [mg/day]). Nitrosureas and mitomycin C must be stopped within 42
             days prior to first dose of GSK3368715.

          -  Allogeneic hematopoietic stem-cell transplantation.

          -  Toxicities from previous anti-cancer therapies have not resolved to Baseline or
             National Cancer Institute (NCI) CTCAE V4.0. <=Grade 1 (except fatigue and alopecia
             [permissible at any grade] and peripheral neuropathy [which must be <= Grade 2]) at
             the time of starting study intervention.

          -  Radiotherapy within 14 days before the initiation of study drug administration (with
             the exception of palliative radiotherapy for pain which can be used any time before
             the first dose of study therapy).

          -  Major surgery (i.e. requiring general anesthesia) within 3 weeks before screening, or
             not fully recovered from major surgery, or major surgery planned during study
             participation. Planned surgical procedures to be conducted under local anesthesia are
             allowed.

          -  Prior organ transplantation.

          -  Concurrent anti-coagulation therapy. Treatment with low-molecular heparin is allowed.

          -  Current use of a prohibited medication or planned use of any forbidden medications
             during intervention with GSK3368715.

          -  History of sensitivity to any of the study medications, or components thereof or a
             history of drug or other allergy that, in the opinion of the investigator or Medical
             Monitor, contraindicates their participation.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Number of subjects with dose limiting toxicity (DLT)
Time Frame:Up to 21 days
Safety Issue:
Description:An adverse event (AE) is considered to be a DLT if the event is considered by the investigator to be clinically relevant and attributed (definitely, probably or possibly) to the study intervention during the first 21 days of intervention and meets DLT criteria for non-hematologic and hematologic Toxicities.

Secondary Outcome Measures

Measure:Part 1: Best overall response
Time Frame:Up to 3.9 years
Safety Issue:
Description:The best overall response is the best response recorded from the start of the intervention until disease progression/initiation of new anti-cancer therapy and will be determined based on the investigators assessment of response at each time point.
Measure:Part 1: Maximum observed plasma concentration (Cmax) following administration of GSK3368715
Time Frame:Pre-dose, 15, 30 minutes (min), 1, 1.5, 2, 3, 4, 6, 8, 12, 24, hours (h) post-dose on Day 1 of each cycle; Pre-dose, 30 min,1,2, 3,4,6,8,12,24 h post-dose on Day 15 of each cycle; Pre-dose at every 4 weeks from Cycle 2 (Each cycle will be of 21 days)
Safety Issue:
Description:Cmax of GSK3368715 is to be derived from the PK samples collected.
Measure:Part 1: Time to reach Cmax (Tmax) following administration of GSK3368715
Time Frame:Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1 of each cycle; Pre-dose, 30 min,1,2, 3,4,6,8,12,24 h post-dose on Day 15 of each cycle; Pre-dose at every 4 weeks from Cycle 2 (Each cycle will be of 21 days)
Safety Issue:
Description:Tmax of GSK3368715 is to be derived from the PK samples collected.
Measure:Part 1: Area under the concentration time curve from time zero to last time of quantifiable concentration (AUC [0-t]) following administration of GSK3368715
Time Frame:Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1 of each cycle; Pre-dose, 30 min,1,2, 3,4,6,8,12,24 h post-dose on Day 15 of each cycle; Pre-dose at every 4 weeks from Cycle 2 (Each cycle will be of 21 days)
Safety Issue:
Description:AUC(0-t) of GSK3368715 is to be derived from the PK samples collected.
Measure:Part 1: AUC from time zero extrapolated to infinite time (AUC [0-infinity]) following single dose administration of GSK3368715
Time Frame:Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1 of each cycle (Each cycle will be of 21 days)
Safety Issue:
Description:AUC(0-infinity) of GSK3368715 is to be derived from the PK samples collected.
Measure:Part 1: Area under the concentration-time curve over the dosing interval (AUC [0-tau]) following repeat dose administration of GSK3368715
Time Frame:Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1; Pre-dose, 30 min,1,2, 3,4,6,8,12,24 h post-dose on Day 15 of each cycle;Pre-dose at every 4 weeks from Cycle 2 (Each cycle will be of 21 days)
Safety Issue:
Description:AUC(0-tau) of GSK3368715 is to be derived from the PK samples collected.
Measure:Part 1: Trough concentration (Ctau) following repeat dose administration of GSK3368715
Time Frame:Pre-dose on Day 8 and Day 15;Pre-dose at every 4 weeks from Cycle 2 (Each cycle will be of 21 days)
Safety Issue:
Description:Ctau of GSK3368715 is to be derived from the PK samples collected.
Measure:Part 1: Time invariance ratio following administration of GSK3368715
Time Frame:Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1; Pre-dose, 30 min, 1, 2, 3, 4, 6, 8, 12, 24 h post-dose on Day 15 of each cycle (Each cycle will be of 21 days)
Safety Issue:
Description:Time invariance ratio of GSK3368715 is to be derived from the PK samples collected wherever data permits.
Measure:Part 1: Accumulation ratio following administration of GSK3368715
Time Frame:Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1; Pre-dose, 30 min, 1, 2, 3, 4, 6, 8, 12, 24 h post-dose on Day 15 of each cycle (Each cycle will be of 21 days)
Safety Issue:
Description:Accumulation ratio of GSK3368715 is to be derived from the PK samples collected wherever data permits.
Measure:Part 2: Number of subjects with AEs and SAEs
Time Frame:Up to 3.9 years
Safety Issue:
Description:An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Any untoward event resulting in death, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.
Measure:Part 2: Number of subjects with AEs by maximum grade
Time Frame:Up to 3.9 years
Safety Issue:
Description:An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AEs will be graded using CTCAE V4.0.
Measure:Part 2: Progression-free survival (PFS)
Time Frame:Up to 3.9 years
Safety Issue:
Description:PFS is defined as the time from the first dose of study intervention to disease progression or death due to any cause, whichever occurs earlier.
Measure:Part 2: Cmax following administration of GSK3368715
Time Frame:Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1 of each cycle; Pre-dose, 30 min,1,2, 3,4,6,8,12,24 h post-dose on Day 15 of each cycle; Pre-dose at every 4 weeks from Cycle 2 (Each cycle will be of 21 days)
Safety Issue:
Description:Cmax of GSK3368715 is to be derived from the PK samples collected.
Measure:Part 2: Tmax following administration of GSK3368715
Time Frame:Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1 of each cycle; Pre-dose, 30 min,1,2, 3,4,6,8,12,24 h post-dose on Day 15 of each cycle; Pre-dose at every 4 weeks from Cycle 2 (Each cycle will be of 21 days)
Safety Issue:
Description:Tmax of GSK3368715 is to be derived from the PK samples collected.
Measure:Part 2: AUC (0-t) following administration of GSK3368715
Time Frame:Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1 of each cycle; Pre-dose, 30 min,1,2, 3,4,6,8,12,24 h post-dose on Day 15 of each cycle; Pre-dose at every 4 weeks from Cycle 2 (Each cycle will be of 21 days)
Safety Issue:
Description:AUC(0-t) of GSK3368715 is to be derived from the PK samples collected.
Measure:Part 2: AUC (0-infinity) following single dose administration of GSK3368715
Time Frame:Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1 of each cycle (Each cycle will be of 21 days)
Safety Issue:
Description:AUC (0-infinity) of GSK3368715 is to be derived from the PK samples collected.
Measure:Part 2: AUC (0-tau) following repeat dose administration of GSK3368715
Time Frame:Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1; Pre-dose, 30 min,1,2, 3,4,6,8,12,24 h post-dose on Day 15 of each cycle; Pre-dose at every 4 weeks from Cycle 2 (Each cycle will be of 21 days)
Safety Issue:
Description:AUC (0-tau) of GSK3368715 is to be derived from the PK samples collected.
Measure:Part 2: Ctau following repeat dose administration of GSK3368715
Time Frame:Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1; Pre-dose, 30 min,1,2, 3,4,6,8,12,24 h post-dose on Day 15 of each cycle; Pre-dose at every 4 weeks from Cycle 2 (Each cycle will be of 21 days)
Safety Issue:
Description:Ctau of GSK3368715 is to be derived from the PK samples collected.
Measure:Part 2: Time invariance ratio following administration of GSK3368715
Time Frame:Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1; Pre-dose, 30 min, 1, 2, 3, 4, 6, 8, 12, 24 h post-dose on Day 15 of each cycle (Each cycle will be of 21 days)
Safety Issue:
Description:Time invariance ratio of GSK3368715 is to be derived from the PK samples collected wherever data permits.
Measure:Part 2: Accumulation ratio following administration of GSK3368715
Time Frame:Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1; Pre-dose, 30 min, 1, 2, 3, 4, 6, 8, 12, 24 h post-dose on Day 15 of each cycle (Each cycle will be of 21 days)
Safety Issue:
Description:Accumulation ratio of GSK3368715 is to be derived from the PK samples collected wherever data permits.

Details

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

Trial Keywords

  • Dose-escalation
  • First time in humans
  • Solid tumors
  • GSK3368715
  • Diffuse Large B-Cell Lymphoma

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