Clinical Trials /

Study Evaluating Safety, Tolerability and Clinical Activity of GSK2857916 in Combination With Pembrolizumab in Subjects With Relapsed/Refractory Multiple Myeloma (RRMM)

NCT03848845

Description:

This is a phase I/II, single arm, open label, two-part study that will assess safety, tolerability and clinical activity of GSK2857916 given in combination with a programmed cell death-1 (PD-1) inhibitor pembrolizumab in subjects with RRMM. This study will enroll adult subjects with RRMM, who have undergone stem cell transplant or who are considered transplant ineligible. Part 1 is a dose escalation phase to evaluate the safety and tolerability of escalating doses of GSK2857916 in combination with 200 milligrams (mg) pembrolizumab to establish the recommended phase 2 dose (RP2D). The following dose levels of GSK2857916 are planned to be studied: 2.5 milligrams per kilograms (mg/kg) (dose level [DL] 1) and 3.4 mg/kg (DL2). Part 2 is a dose expansion cohort. Once the RP2D has been identified, an expansion cohort will open for enrolment to confirm the safety profile and to evaluate the clinical activity of the combination. Up to 40 evaluable subjects will be enrolled in this two-part study (up to 12 in Part 1, and 28 in Part 2).

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study Evaluating Safety, Tolerability and Clinical Activity of GSK2857916 in Combination With Pembrolizumab in Subjects With Relapsed/Refractory Multiple Myeloma (RRMM)
  • Official Title: A Phase I/II Single Arm Open-Label Study to Explore Safety and Clinical Activity of GSK2857916 Administered in Combination With Pembrolizumab in Subjects With Relapsed/Refractory Multiple Myeloma (DREAMM 4)

Clinical Trial IDs

  • ORG STUDY ID: 205207
  • NCT ID: NCT03848845

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
GSK2857916Part 1: Dose escalation
PembrolizumabPart 1: Dose escalation

Purpose

This is a phase I/II, single arm, open label, two-part study that will assess safety, tolerability and clinical activity of GSK2857916 given in combination with a programmed cell death-1 (PD-1) inhibitor pembrolizumab in subjects with RRMM. This study will enroll adult subjects with RRMM, who have undergone stem cell transplant or who are considered transplant ineligible. Part 1 is a dose escalation phase to evaluate the safety and tolerability of escalating doses of GSK2857916 in combination with 200 milligrams (mg) pembrolizumab to establish the recommended phase 2 dose (RP2D). The following dose levels of GSK2857916 are planned to be studied: 2.5 milligrams per kilograms (mg/kg) (dose level [DL] 1) and 3.4 mg/kg (DL2). Part 2 is a dose expansion cohort. Once the RP2D has been identified, an expansion cohort will open for enrolment to confirm the safety profile and to evaluate the clinical activity of the combination. Up to 40 evaluable subjects will be enrolled in this two-part study (up to 12 in Part 1, and 28 in Part 2).

Trial Arms

NameTypeDescriptionInterventions
Part 1: Dose escalationExperimentalSubjects will receive GSK2857916 at escalating doses of 2.5 milligrams per kilograms (mg/kg) and 3.4 mg/kg along with 200 mg pembrolizumab via intravenous (IV) infusion on Day 1 of each 21-day cycle to establish RP2D. There will be maximum of 35 cycles of combination treatment.
  • GSK2857916
  • Pembrolizumab
Part 2: Expansion cohortExperimentalSubjects will receive GSK2857916 at RP2D along with 200 mg pembrolizumab via IV infusion on Day 1 of each 21-day cycle. There will be maximum of 35 cycles of combination treatment.
  • GSK2857916
  • Pembrolizumab

Eligibility Criteria

        Inclusion criteria:

          -  Provide signed written informed consent, which includes compliance with the
             requirements and restrictions listed in the consent form.

          -  Male or female, 18 years or older (at the time consent is obtained).

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          -  Subjects must: have histologically or cytologically confirmed diagnosis of Multiple
             myeloma (MM), as defined by IMWG, 2014 and has undergone stem cell transplant or is
             considered transplant ineligible, and has been treated with at least 3 prior lines of
             prior anti-myeloma treatments including an immunomodulatory imide drug (IMiD) (eg.
             lenalidomide or pomalidomide), a proteasome inhibitor (eg. bortezomib, ixazomib or
             carfilzomib) and an anti-CD38 antibody alone or in combination. Line of therapy are
             defined by consensus panel of the International Myeloma Workshop, Has measurable
             disease defined as one the following: a) Serum M-protein >=0.5 grams per deciliter
             (g/dL) (>=5 grams per liter [g/L]). b) Urine M-protein ≥200 mg/24h. c) Serum Free
             light chain (FLC) assay: Involved FLC level ≥10 milligrams per deciliter (mg/dL) (≥100
             milligrams per liter [mg/L]) and an abnormal serum free light chain ratio (<0.26 or
             >1.65).

          -  Subjects with a history of autologous stem cell transplant are eligible for study
             participation provided the following eligibility criteria are met: a) transplant was >
             100 days prior to study enrolment. b) no active infection(s). c) subject meets the
             remainder of the eligibility criteria.

          -  Adequate organ system functions as defined by the laboratory assessments.

          -  All prior treatment-related toxicities (defined by National Cancer Institute-Common
             Toxicity Criteria for Adverse Events [NCI-CTCAE], version 4.03, 2010) must be <= Grade
             1 at the time of enrolment except for alopecia and Grade 2 neuropathy.

          -  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% per year), preferably with low user dependency,
             during the intervention period and for at least 120 days after the last dose of study
             intervention 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 intervention. A
             WOCBP must have a negative highly sensitive serum pregnancy test (as required by local
             regulations) within 72 hours 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 140 days after the last dose of study
             intervention. Male subjects should refrain from donating sperm, plus, either be
             abstinent from heterosexual 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 a male condom and female partner to use an additional highly effective
             contraceptive method with a failure rate of <1% per year when having sexual
             intercourse with a woman of childbearing potential who is not currently pregnant.

        Exclusion criteria:

        A subject will NOT be eligible for inclusion in this study if any of the following criteria
        apply:

          -  Systemic anti-myeloma therapy or an investigational drug <=14 days or five half-lives,
             whichever is shorter, preceding the first dose of study drug

          -  Plasmapheresis within 7 days prior to the first dose of study drug

          -  Prior treatment with a monoclonal antibody within 30 days of receiving the first dose
             of study drugs

          -  Has received prior therapy with an anti-PD-1, anti-Programmed cell death Ligand 1
             (PD-L1), or anti-Programmed cell death Ligand 2 (PD-L2) agent or with an agent
             directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic
             T-lymphocyte-associated antigen 4 [CTLA-4], OX 40, CD137) and was discontinued from
             that treatment due to a Grade 3 or higher immune related adverse event (irAE)

          -  Current corneal epithelial disease except mild punctate keratopathy

          -  Any major surgery within the last four weeks prior to the first dose of study therapy

          -  Presence of active renal condition (infection, requirement for dialysis or any other
             condition that could affect subject's safety). Subjects with isolated proteinuria
             resulting from MM are eligible, provided they fulfil criteria as per adequate organ
             system function mentioned under inclusion criteria.

          -  Any serious and/or unstable pre-existing medical, psychiatric disorder or other
             conditions (including lab abnormalities) that could interfere with subject's safety,
             obtaining informed consent or compliance to the study procedures.

          -  Has received prior radiotherapy within 2 weeks of start of study therapy. Subjects
             must have recovered from all radiation-related toxicities, not require
             corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
             for palliative radiation (<=2 weeks of radiotherapy) to non-central nervous system
             (CNS) disease.

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

          -  Current active liver or biliary disease per investigator assessment defined by the
             presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or
             gastric varices, persistent jaundice, or cirrhosis.

          -  Malignancies other than disease under study are excluded, except for 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 GSK Medical Monitor, will not affect
             the evaluation of the effects of this clinical trial treatment on the currently
             targeted malignancy (RRMM). Subjects with curatively treated non-melanoma skin cancer
             are allowed.

          -  Has known active CNS metastases and/or carcinomatous meningitis. Subjects with
             previously treated brain metastases may participate provided they are radiologically
             stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging
             (note that the repeat imaging should be performed during study screening), clinically
             stable and without requirement of steroid treatment for at least 14 days prior to
             first dose of study therapy

          -  Evidence of cardiovascular risk including any of the following: a) corrected for heart
             rate by Fridericia's formula (QTcF) interval ≥470 msecs. b) Evidence of current
             clinically significant uncontrolled arrhythmias; i. including clinically significant
             ECG abnormalities including 2nd degree (Type II) or 3rd degree atrioventricular (AV)
             block. c) History of myocardial infarction, acute coronary syndromes (including
             unstable angina), coronary angioplasty, or stenting or bypass grafting within six
             months of Screening. d) Class III or IV heart failure as defined by the New York Heart
             Association functional classification system. e) Uncontrolled hypertension. f)
             Presence of cardiac pacemaker (or defibrillator) with a predominantly ventricular
             paced rhythm, limiting ECG/QTcF analysis. g) Abnormal cardiac valve morphology
             (>=Grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e.,
             mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular
             thickening should not be entered on study.

          -  Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
             chemically related to GSK2857916 or pembrolizumab, or any of the components of the
             study treatment.

          -  Pregnant or lactating female.

          -  Known active infection requiring antibiotic, antiviral, or antifungal treatment.

          -  Known Human Immunodeficiency Virus (HIV) infection.

          -  Presence of hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb)
             at screening or within 3 months prior to first dose of study treatment

          -  Positive hepatitis C antibody test result or positive hepatitis C Ribonucleic acid
             (RNA) test result at screening or within 3 months prior to first dose of study
             treatment.

          -  Has received a live-virus vaccination within 30 days of planned start of study
             therapy.

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

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other chronic form
             of immunosuppressive therapy within 7 days prior the first dose of study therapy.

          -  Has known psychiatric or substance abuse disorder that would interfere with the
             subject's ability to cooperate with the requirements of the study.

          -  Has had an allogenic tissue/solid organ transplant
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Percentage of subjects with adverse events (AEs) and serious adverse events (SAEs)
Time Frame:Up to 3 years
Safety Issue:
Description:An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function.

Secondary Outcome Measures

Measure:Part 1: Overall response rate
Time Frame:Up to 3 years
Safety Issue:
Description:Overall Response rate is defined as the percentage of subjects with a confirmed PR or better (i.e., PR, VGPR, CR and sCR), according to the IMWG Response Criteria.
Measure:Part 1: Area under the concentration-time curve AUC(0-t) following IV administration of GSK2857916 in combination with pembrolizumab after the first dose
Time Frame:Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 and 15 of Cycle 1 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.
Measure:Part 1: AUC (0-tau) following IV administration of GSK2857916 in combination with pembrolizumab after the first dose
Time Frame:Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 and 15 of Cycle 1 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.
Measure:Part 1: AUC(0-infinity) following IV administration of GSK2857916 in combination with pembrolizumab after the first dose
Time Frame:Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 and 15 of Cycle 1 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.
Measure:Part 1: Maximum concentration (Cmax) following IV administration of GSK2857916 in combination with pembrolizumab after the first dose
Time Frame:Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 and 15 of Cycle 1 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.
Measure:Part 1: Time of Cmax (tmax) following IV administration of GSK2857916 in combination with pembrolizumab after the first dose
Time Frame:Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 and 15 of Cycle 1 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.
Measure:Part 1: Last time point where the concentration is above the limit of quantification (tlast) following IV administration of GSK2857916 in combination with pembrolizumab after the first dose
Time Frame:Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 and 15 of Cycle 1 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.
Measure:Part 1: Terminal phase elimination rate constant (Lambda Z) following IV administration of GSK2857916 in combination with pembrolizumab after the first dose
Time Frame:Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 and 15 of Cycle 1 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.
Measure:Part 1: Terminal phase half-life (t1/2) following IV administration of GSK2857916 in combination with pembrolizumab after the first dose
Time Frame:Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 and 15 of Cycle 1 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.
Measure:Part 1: Concentration at trough (Ctrough) following IV administration of GSK2857916 in combination with pembrolizumab for Cycles 2 and 5
Time Frame:Pre-dose (prior to start of infusion) and end of infusion after GSK2857916 and pembrolizumab of Cycles 2 and 5 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.
Measure:Part 1: Ctrough following IV administration of GSK2857916 for Cycles 8 and 11
Time Frame:Pre-dose (prior to start of infusion) and end of infusion after GSK2857916 of Cycles 8 and 11 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously.
Measure:Part 1: Ctrough following IV administration of GSK2857916 for Cycle 14 and every 3 Cycles until Cycle 35
Time Frame:Pre-dose (prior to start of infusion) after GSK2857916 of Cycles 14 and every 3 Cycles until Cycle 35 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously.
Measure:Part 1: End of infusion concentration following IV administration of GSK2857916 in combination with pembrolizumab
Time Frame:Pre-dose (prior to start of infusion) and end of infusion after GSK2857916 and pembrolizumab of Cycles 2, 5, 8, 11, 14 and every 3 Cycles until Cycle 35 (Each cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.
Measure:Part 1: Number of subjects with positive anti-drug antibodies (ADAs) against GSK2857916
Time Frame:Up to 3 years
Safety Issue:
Description:Samples will be taken from all the subjects to analyze for the presence of ADAs using validated immunoassays.
Measure:Part 1: Titers of ADAs against GSK2857916
Time Frame:Up to 3 years
Safety Issue:
Description:Samples will be taken from all the subjects to analyze for the presence of ADAs using validated immunoassays. All samples will be tested in screening assay, and positive samples will be further characterized for antibody titers.
Measure:Part 2: Number of subjects with AEs and SAEs
Time Frame:Up to 3 years
Safety Issue:
Description:An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function.
Measure:Part 2: Number of subjects with abnormal hematology parameters
Time Frame:Up to 3 years
Safety Issue:
Description:Blood samples will be collected to measure platelets, WBC count, RBC count, reticulocyte count, hemoglobin, hematocrit, , RBC indices, MCV, MCH, MCHC, basophils, eosinophils, lymphocytes, monocytes and neutrophils.
Measure:Part 2: Number of subjects with abnormal clinical chemistry parameters
Time Frame:Up to 3 years
Safety Issue:
Description:Blood samples will be collected to measure BUN, creatinine, fasting glucose, sodium, magnesium, potassium, chloride, calcium, phosphorus, troponin, uric acid, triglycerides, AST, ALT, alkaline phosphatase, total and direct bilirubin, albumin, CK, Total CO2/bicarbonate and total protein.
Measure:Part 2: Number of subjects with abnormal urinalysis results
Time Frame:Up to 3 years
Safety Issue:
Description:Samples will be collected to measure specific gravity, pH, glucose, protein, blood and ketones by dipstick method.
Measure:Part 2: Number of subjects with abnormal SBP and DBP
Time Frame:Up to 3 years
Safety Issue:
Description:The number of subjects with abnormal SBP and DBP will be measured in a semi-supine position after 5 minutes rest.
Measure:Part 2: Number of subjects with abnormal pulse rate
Time Frame:Up to 3 years
Safety Issue:
Description:The number of subjects with abnormal pulse rate will be measured in a semi-supine position after 5 minutes rest.
Measure:Part 2: Number of subjects with abnormal body temperature
Time Frame:Up to 3 years
Safety Issue:
Description:The number of subjects with abnormal body temperature will be measured in a semi-supine position after 5 minutes rest.
Measure:Part 2: Number of subjects with ocular findings on ophthalmic exam
Time Frame:Up to 3 years
Safety Issue:
Description:A full ophthalmic examination for all subjects will be conducted for any abnormal ocular findings.
Measure:Part 2: Clinical benefit rate
Time Frame:Up to 3 years
Safety Issue:
Description:Clinical benefit rate is defined as the percentage of subjects with a confirmed minimal response (MR) or better according to the IMWG Response Criteria.
Measure:Part 2: Duration of response
Time Frame:Up to 3 years
Safety Issue:
Description:Duration of response is defined as the time from first documented evidence of PR or better, to the time when disease progression (PD) is documented per IMWG response criteria; or death due to PD occurs among subjects who achieve an overall response, i.e. confirmed PR or better.
Measure:Part 2: Time to response
Time Frame:Up to 3 years
Safety Issue:
Description:Time to response is defined as the time between the date of first dose and the first documented evidence of response (PR or better) among subjects who achieved a confirmed response of PR or better.
Measure:Part 2: Time to best response
Time Frame:Up to 3 years
Safety Issue:
Description:Time to best response is defined as the time between the date of first dose and the first best documented response (PR or better) among subjects who achieved a confirmed response of PR or better.
Measure:Part 2: Progression-free survival
Time Frame:Up to 3 years
Safety Issue:
Description:Progression-free survival is defined as the time from first dose until the earliest date of PD per IMWG response criteria, or death due to any cause.
Measure:Part 2: Time to disease progression
Time Frame:Up to 3 years
Safety Issue:
Description:Time to disease progression is defined as the time from first dose until the earliest date of PD per IMWG response criteria, or death due to PD.
Measure:Part 2: Overall Survival
Time Frame:Up to 3 years
Safety Issue:
Description:Overall Survival is defined as the time from first dose until death due to any cause.
Measure:Part 2: AUC(0-t) following IV administration of GSK2857916 in combination with pembrolizumab after the first dose
Time Frame:Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 and 15 of Cycle 1 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.
Measure:Part 2: AUC (0-tau) following IV administration of GSK2857916 in combination with pembrolizumab after the first dose
Time Frame:Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 and 15 of Cycle 1 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.
Measure:Part 2: AUC(0-infinity) following IV administration of GSK2857916 in combination with pembrolizumab after the first dose
Time Frame:Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 and 15 of Cycle 1 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.
Measure:Part 2: Cmax following IV administration of GSK2857916 in combination with pembrolizumab after the first dose
Time Frame:Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 and 15 of Cycle 1 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.
Measure:Part 2: tmax following IV administration of GSK2857916 in combination with pembrolizumab after the first dose
Time Frame:Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 and 15 of Cycle 1 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.
Measure:Part 2: Tlast following IV administration of GSK2857916 in combination with pembrolizumab after the first dose
Time Frame:Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 and 15 of Cycle 1 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.
Measure:Part 2: Lambda Z following IV administration of GSK2857916 in combination with pembrolizumab after the first dose
Time Frame:Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 and 15 of Cycle 1 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.
Measure:Part 2: t1/2 following IV administration of GSK2857916 in combination with pembrolizumab after the first dose
Time Frame:Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 and 15 of Cycle 1 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.
Measure:Part 2: Ctrough following IV administration of GSK2857916 in combination with pembrolizumab for Cycles 2 and 5
Time Frame:Pre-dose (prior to start of infusion) and end of infusion after GSK2857916 and pembrolizumab of Cycles 2 and 5 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.
Measure:Part 2: Ctrough following IV administration of GSK2857916 for Cycles 8 and 11
Time Frame:Pre-dose (prior to start of infusion) and end of infusion after GSK2857916 of Cycles 8 and 11 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously.
Measure:Part 2: Ctrough following IV administration of GSK2857916 for Cycle 14 and every 3 Cycles until Cycle 35
Time Frame:Pre-dose (prior to start of infusion) after GSK2857916 of Cycle 14 and every 3 Cycles until Cycle 35 (Each Cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously.
Measure:Part 2: End of infusion concentration following IV administration of GSK2857916 in combination with pembrolizumab
Time Frame:Pre-dose (prior to start of infusion) and end of infusion after GSK2857916 and pembrolizumab of Cycles 2, 5, 8, 11, 14 and every 3 Cycles until Cycle 35 (Each cycle will be of 21 days)
Safety Issue:
Description:Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.
Measure:Part 2: Number of subjects with positive ADAs against GSK2857916
Time Frame:Up to 3 years
Safety Issue:
Description:Samples will be taken from all the subjects to analyze for the presence of ADAs using validated immunoassays.
Measure:Part 2: Titers of ADAs against GSK2857916
Time Frame:Up to 3 years
Safety Issue:
Description:Samples will be taken from all the subjects to analyze for the presence of ADAs using validated immunoassays. All samples will be tested in screening assay, and positive samples will be further characterized for antibody titers.

Details

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

Trial Keywords

  • GSK2857916, Pembrolizumab, Multiple Myeloma, RP2D

Last Updated

October 16, 2019