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Study Evaluating Safety, Tolerability and Clinical Activity of GSK2857916 in Combination With Pembrolizumab in Subjects With Relapsed/Refractory Multiple Myeloma (RRMM) (DREAMM 4)

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ClinicalTrials.gov Identifier: NCT03848845
Recruitment Status : Recruiting
First Posted : February 21, 2019
Last Update Posted : August 9, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: GSK2857916 Drug: Pembrolizumab Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Subjects will receive GSK2857916 at escalating doses along with pembrolizumab on Day 1 of each 21-day Cycle to establish RP2D during the Part 1 of the study. Subjects will receive GSK2857916 at RP2D along with pembrolizumab on Day 1 of each 21-day Cycle in Part 2 of the study.
Masking: None (Open Label)
Masking Description: This will be an open-label study. Hence, there will be no masking.
Primary Purpose: Treatment
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)
Actual Study Start Date : March 14, 2019
Estimated Primary Completion Date : August 31, 2023
Estimated Study Completion Date : August 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Part 1: Dose escalation
Subjects 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.
Drug: GSK2857916
GSK2857916 will be available as 20 milligrams per millilitre (mg/mL) solution for IV infusion, supplied as frozen liquid. GSK2857916 solution will be diluted in normal 0.9% saline to the appropriate concentration for the dose.

Drug: Pembrolizumab
Pembrolizumab will be available as 100 mg/4 mL solution that should be stored under refrigeration at 2-8 degree Celsius. Pembrolizumab injection (solution) will be diluted prior to IV administration in 0.9% sodium chloride injection or 5% dextrose injection.

Experimental: Part 2: Expansion cohort
Subjects 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.
Drug: GSK2857916
GSK2857916 will be available as 20 milligrams per millilitre (mg/mL) solution for IV infusion, supplied as frozen liquid. GSK2857916 solution will be diluted in normal 0.9% saline to the appropriate concentration for the dose.

Drug: Pembrolizumab
Pembrolizumab will be available as 100 mg/4 mL solution that should be stored under refrigeration at 2-8 degree Celsius. Pembrolizumab injection (solution) will be diluted prior to IV administration in 0.9% sodium chloride injection or 5% dextrose injection.




Primary Outcome Measures :
  1. Part 1: Percentage of subjects with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 3 years ]
    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.

  2. Part 1: Number of subjects with abnormal hematology parameters [ Time Frame: Up to 3 years ]
    Blood samples will be collected to measure platelets, white blood cell (WBC count), red blood cell (RBC) count, reticulocyte count, hemoglobin, hematocrit, RBC indices, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), basophils, eosinophils, lymphocytes, monocytes and neutrophils.

  3. Part 1: Number of subjects with abnormal clinical chemistry parameters [ Time Frame: Up to 3 years ]
    Blood samples will be collected to measure blood urea nitrogen (BUN), creatinine, fasting glucose, sodium, magnesium, potassium, chloride, calcium, phosphorus, troponin, uric acid, triglycerides, Aspartate aminotransferase (AST), ALT, alkaline phosphatase, total and direct bilirubin, albumin, creatinine kinase (CK), total carbon dioxide (CO2)/bicarbonate and total protein.

  4. Part 1: Number of subjects with abnormal urinalysis results [ Time Frame: Up to 3 years ]
    Samples will be collected to measure specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick method.

  5. Part 1: Number of subjects with abnormal systolic blood pressure (SBP) and diastolic blood pressure (DBP) [ Time Frame: Up to 3 years ]
    The number of subjects with abnormal SBP and DBP will be measured in a semi-supine position after 5 minutes rest.

  6. Part 1: Number of subjects with abnormal pulse rate [ Time Frame: Up to 3 years ]
    The number of subjects with abnormal pulse rate will be measured in a semi-supine position after 5 minutes rest.

  7. Part 1: Number of subjects with abnormal body temperature [ Time Frame: Up to 3 years ]
    The number of subjects with abnormal body temperature will be measured in a semi-supine position after 5 minutes rest.

  8. Part 1: Number of subjects with dose limiting toxicities (DLTs) [ Time Frame: Up to 21 days ]
    A DLT is an AE that is considered by the investigator to be clinically relevant and attributed to the study therapy during the 21 day DLT period and meets at least one of the criteria: any Grade 4 and 3 non-hematologic toxicity, any Grade 3 or greater non-hematologic laboratory value, hematologic toxicity lasting >=7 days, except Grade 4 thrombocytopenia of any duration or Grade 3 thrombocytopenia associated with clinically significant bleeding. Grade 3 or greater febrile neutropenia lasting >48 hours despite adequate treatment, Nephrotoxicity requiring dialysis, Liver toxicity, prolonged delay (>14 days) in initiating Cycle 2 due to any treatment (pembrolizumab or GSK2857916) related toxicity, any treatment-related toxicity that causes discontinuation of treatment during Cycle 1, any other toxicity considered to be dose-limiting that occurs beyond 21 days and any other event which in the judgment of the investigator and GlaxoSmithKline Medical Monitor is considered to be a DLT.

  9. Part 2: Overall Response Rate [ Time Frame: Up to 3 years ]
    Overall Response rate is defined as the percentage of subjects with a confirmed partial response (PR) or better (i.e., PR, very good partial response [VGPR], complete response [CR] and stringent complete response [sCR]), according to the International Myeloma Working Group (IMWG) Response Criteria.


Secondary Outcome Measures :
  1. Part 1: Overall response rate [ Time Frame: Up to 3 years ]
    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.

  2. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.

  3. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.

  4. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.

  5. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.

  6. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.

  7. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.

  8. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.

  9. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.

  10. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.

  11. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously.

  12. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously.

  13. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.

  14. Part 1: Number of subjects with positive anti-drug antibodies (ADAs) against GSK2857916 [ Time Frame: Up to 3 years ]
    Samples will be taken from all the subjects to analyze for the presence of ADAs using validated immunoassays.

  15. Part 1: Titers of ADAs against GSK2857916 [ Time Frame: Up to 3 years ]
    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.

  16. Part 2: Number of subjects with AEs and SAEs [ Time Frame: Up to 3 years ]
    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.

  17. Part 2: Number of subjects with abnormal hematology parameters [ Time Frame: Up to 3 years ]
    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.

  18. Part 2: Number of subjects with abnormal clinical chemistry parameters [ Time Frame: Up to 3 years ]
    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.

  19. Part 2: Number of subjects with abnormal urinalysis results [ Time Frame: Up to 3 years ]
    Samples will be collected to measure specific gravity, pH, glucose, protein, blood and ketones by dipstick method.

  20. Part 2: Number of subjects with abnormal SBP and DBP [ Time Frame: Up to 3 years ]
    The number of subjects with abnormal SBP and DBP will be measured in a semi-supine position after 5 minutes rest.

  21. Part 2: Number of subjects with abnormal pulse rate [ Time Frame: Up to 3 years ]
    The number of subjects with abnormal pulse rate will be measured in a semi-supine position after 5 minutes rest.

  22. Part 2: Number of subjects with abnormal body temperature [ Time Frame: Up to 3 years ]
    The number of subjects with abnormal body temperature will be measured in a semi-supine position after 5 minutes rest.

  23. Part 2: Number of subjects with ocular findings on ophthalmic exam [ Time Frame: Up to 3 years ]
    A full ophthalmic examination for all subjects will be conducted for any abnormal ocular findings.

  24. Part 2: Clinical benefit rate [ Time Frame: Up to 3 years ]
    Clinical benefit rate is defined as the percentage of subjects with a confirmed minimal response (MR) or better according to the IMWG Response Criteria.

  25. Part 2: Duration of response [ Time Frame: Up to 3 years ]
    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.

  26. Part 2: Time to response [ Time Frame: Up to 3 years ]
    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.

  27. Part 2: Time to best response [ Time Frame: Up to 3 years ]
    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.

  28. Part 2: Progression-free survival [ Time Frame: Up to 3 years ]
    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.

  29. Part 2: Time to disease progression [ Time Frame: Up to 3 years ]
    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.

  30. Part 2: Overall Survival [ Time Frame: Up to 3 years ]
    Overall Survival is defined as the time from first dose until death due to any cause.

  31. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.

  32. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.

  33. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.

  34. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.

  35. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.

  36. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.

  37. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.

  38. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.

  39. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.

  40. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously.

  41. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously.

  42. 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) ]
    Blood samples will be collected for PK analysis of GSK2857916 when administered intravenously in combination with pembrolizumab.

  43. Part 2: Number of subjects with positive ADAs against GSK2857916 [ Time Frame: Up to 3 years ]
    Samples will be taken from all the subjects to analyze for the presence of ADAs using validated immunoassays.

  44. Part 2: Titers of ADAs against GSK2857916 [ Time Frame: Up to 3 years ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03848845


Contacts
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Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations
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United States, Georgia
GSK Investigational Site Recruiting
Atlanta, Georgia, United States, 30322
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Ajay Nooka         
United States, Indiana
GSK Investigational Site Recruiting
Indianapolis, Indiana, United States, 46202
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Attaya Suvannasankha         
Canada, Alberta
GSK Investigational Site Recruiting
Calgary, Alberta, Canada, T2N 2T9
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Nizar Jacques Bahlis         
Canada, Ontario
GSK Investigational Site Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Suzanne Trudel         
Spain
GSK Investigational Site Recruiting
Pozuelo De Alarcón/Madrid, Spain, 28223
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Aránzazu Alonso Alonso         
GSK Investigational Site Recruiting
Salamanca, Spain, 37007
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: María Victoria Mateos Manteca         
Sponsors and Collaborators
GlaxoSmithKline
Merck Sharp & Dohme Corp.
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline

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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03848845     History of Changes
Other Study ID Numbers: 205207
First Posted: February 21, 2019    Key Record Dates
Last Update Posted: August 9, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
GSK2857916, Pembrolizumab, Multiple Myeloma, RP2D
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents