Clinical trial NCT02064387: Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of GSK2857916
Official title: A Phase I Open-label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of the Antibody Drug Conjugate GSK2857916 in Subjects With Relapsed/Refractory Multiple Myeloma and Other Advanced Hematologic Malignancies Expressing BCMA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
BCMA expressing Lymphomas
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2014-02-17
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will assess the safety, pharmacokinetic (PK), pharmacodynamic (PD) and the therapeutic potential of GSK2857916 in subjects with multiple myeloma (MM) and lymphomas that express B cell maturation antigen (BCMA). The hypothesis is that GSK2857916 can be safely administered to subjects with MM and with BCMA positive malignancies at doses where target engagement can be demonstrated. This study will determine if adequate target engagement of BCMA receptors translates into clinical benefit for subjects with MM and BCMA positive lymphomas. The study will consists of two parts: a Part 1 dose escalation phase and a Part 2 expansion phase for safety, tolerability, PK, PD, and clinical activity testing. The study will enroll a total of approximately 80-95 subjects with relapsed/refractory MM or BCMA-expressing hematologic malignancies. The maximum dose to be administered in this trial will not exceed 5 milligram/kilogram(mg/kg).


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.
* Part 1/dose escalation; Histologically or cytologically confirmed diagnosis of Multiple Myeloma in a subject who fulfills all of the following: has undergone stem cell transplant, or is considered transplant ineligible, has been pretreated with at least the 3 following classes of anti-myeloma drugs: alkylators, proteasome inhibitors and immunomodulators, has demonstrated progression on, or within 60 days of completion of the last therapy.

Part 2 /MM cohort; Histologically or cytologically confirmed diagnosis of: Multiple Myeloma in a subject who fulfills all of the following: has undergone stem cell transplant, or is considered transplant ineligible, has been pretreated with at least the 3 following classes of anti-myeloma drugs: alkylators, proteasome inhibitors and immunomodulators, has demonstrated progression on, or within 60 days of completion of the last therapy, and has measurable disease with at least one of the following: serum M-protein \>=0.5 gram (g)/decilitre (dL) (\>=5 g/Litre (L)), urine M-protein \>=200 milligram (mg)/24hour (h).

Serum free light chain (FLC) assay: Involved FLC level \>=5 mg/dL (\>=50 mg/L) and an abnormal serum FLC ratio (\<0.26 or \>1.65) and biopsy proven plasmacytoma (should be measured within 28 days of Screening Visit).

* Part 2/Other BCMA positive Hematologic Malignancies cohort: Subject with one of the following lymphomas: Diffuse Large B-cell Lymphoma (DLBCL) or follicular lymphoma (FL) that exhibits positive BCMA expression on tumor cells as determined by a central laboratory using a validated Immunohistochemistry (IHC) assay. Eligible subjects with BCMA positive malignancies must also fulfill the prior treatment requirements as follows: DLBCL: at least 2 prior lines of systemic therapy containing at least one line of chemo-immunotherapy with anti-CD20 antibody, and either has undergone stem cell transplant or is considered transplant ineligible. FL: at least 2 prior lines of systemic therapy.
* Subjects with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met: transplant was \> 100 days prior to study enrolment, no active infection; subject meets the remainder of the eligibility criteria outlined in the study protocol.
* Adequate organ system functions as defined below Absolute neutrophil count\>=1.0x10\^9/L, hemoglobin\>=8.0 g/dL, platelet\>=50x10\^9/L, international normalized ration (INR) \<=1.5, Partial thromboplastin time \<=1.5xupper limit of normal (ULN), total bilirubin \<=1.25xULN, alanine aminotransferase and aspartate aminotransferase\<=1.5 X ULN, serum creatinine or calculated creatinine clearance\<1.2XULN \>=60 mL/min for Part 1;\>=50 mL/minute (min) for Part 2 if data supports loosening criteria, Albuminuria\<=500 mg/24h, left ventricular ejection fraction \>=50%, Troponin\<=1xULN, Calcium\<=1.1xULN
* A female subject is eligible to participate if she is of: Non-childbearing potential or women of childbearing potential must have a negative serum pregnancy test within 72 hours of first dose of study treatment and agree to use effective contraception during the study and for 60 days following the last dose of study treatment.
* Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from the time of first dose of study until 60 days after the last dose of study treatment to allow for clearance of any altered sperm
* All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events, version 4) must be \<=Grade 1 at the time of enrollment except for alopecia, and grade 2 neuropathy.

Exclusion Criteria:

* Systemic anti-tumor therapy within 14 days, or plasmapheresis within 7 days prior to the first dose of study drug
* Use of an investigational drug within 14 days or five half-lives, whichever is shorter, preceding the first dose of study drug. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drug.
* History of an allogeneic stem cell transplant. Subjects with a history of an autologous stem cell transplant are NOT excluded if they meet inclusion criteria related to history of autologous stem cell transplant.
* 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 the inclusion criteria related to organ system function.
* Evidence of active mucosal or internal bleeding
* Any major surgery within the last four weeks.
* 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.
* Known active infection requiring antibiotic treatment
* Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal or cardiac disease
* Subjects with previous or concurrent malignancies are allowed only if the second tumor is not contributing to the subject's illness. The subject must not be receiving active therapy, other than hormonal therapy for this disease and the disease must be considered medically stable for at least 2 years.
* Evidence of cardiovascular risk including any of the following: QT interval corrected\>=470 millisecond, evidence of current clinically significant uncontrolled arrhythmias, history of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening, Class III or IV heart failure as defined by the New York Heart Association functional classification system, uncontrolled hypertension, subjects with intra-cardiac defibrillators or permanent pacemakers, 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 any of the components of the study treatment.
* Pregnant or lactating female.
* Known human immuno virus infection.
* Subjects with positive test for Hepatitis B surface (HBS-Ag) or Hepatitis B core (HBc)antigen
* Subjects with positive test for hepatitis C (HCV) infection are excluded regardless of viral load. If hepatitis C antibody test is positive, a confirmatory polymerase chain reaction (PCR) or Recombinant immunoblot assay (RIBA) test should be performed. If the PCR or RIBA test is negative, subject is eligible for this trial
* Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator's assessment).
* Current corneal disease or a history of corneal disease.

Primary outcomes:
measure: Number of Participants With Serious Adverse Events (SAEs) and Common (>=5%) Non-serious Adverse Events- Part 1
timeFrame: Up to 23.5 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With SAEs and Common (>=5%) Non-serious Adverse Events- Part 2 (MM)
timeFrame: Up to 35 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With SAEs and Common (>=5%) Non-serious Adverse Events- Part 2 (NHL)
timeFrame: Up to 7.2 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Dose-limiting Toxicities (DLTs) During the Determinative Period- Part 1
timeFrame: Up to Day 21 (from first dose)
measure: Number of Participants With Grade Change From Baseline in Vital Signs-DBP & SBP-Part 1
timeFrame: Baseline and Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Grade Change From Baseline in Vital Signs-DBP & SBP-Part 2 (MM)
timeFrame: Baseline and Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Grade Change From Baseline in Vital Signs-DBP & SBP-Part 2 (NHL)
timeFrame: Up to 7.2 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Change From Baseline in Heart Rate and Temperature-Part 1
timeFrame: Baseline and Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Change From Baseline in Heart Rate and Temperature-Part 2 (MM)
timeFrame: Baseline and Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Change From Baseline in Heart Rate and Temperature-Part 2 (NHL)
timeFrame: Baseline and Up to 7.2 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Grade Change From Baseline in Clinical Chemistry Data-Part 1
timeFrame: Baseline and Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Grade Change From Baseline in Clinical Chemistry Data-Part 2 (MM)
timeFrame: Baseline and Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Grade Change From Baseline in Clinical Chemistry Data-Part 2 (NHL)
timeFrame: Baseline and Up to 7.2 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Change From Baseline in Clinical Chemistry Data With Respect to Normal Range-Part 1
timeFrame: Baseline and Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Change From Baseline in Clinical Chemistry Data With Respect to Normal Range-Part 2 (MM)
timeFrame: Baseline and Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Change From Baseline in Clinical Chemistry Data With Respect to Normal Range-Part 2 (NHL)
timeFrame: Baseline and Up to 7.2 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Grade Change From Baseline in Hematology Data-Part 1
timeFrame: Baseline and Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Grade Change From Baseline in Hematology Data-Part 2 (MM)
timeFrame: Baseline and Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Grade Change From Baseline in Hematology Data-Part 2 (NHL)
timeFrame: Baseline and Up to 7.2 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Change From Baseline in Hematology Data With Respect to Normal Range-Part 1
timeFrame: Baseline and Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Change From Baseline in Hematology Data With Respect to Normal Range-Part 2 (MM)
timeFrame: Baseline and Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Change From Baseline in Hematology Data With Respect to Normal Range-Part 2 (NHL)
timeFrame: Baseline and Up to 7.2 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method -Part 1
timeFrame: Baseline and Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method -Part 2 (MM)
timeFrame: Baseline and Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method -Part 2 (NHL)
timeFrame: Baseline and Up to 7.2 months (maximum duration of follow-up from first dose to last contact or death)
measure: Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 0.06 mg/kg
timeFrame: Baseline and Day 1 (Cycle 2 and 3)
measure: Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 0.03 mg/kg and 0.12 mg/kg
timeFrame: Baseline and Day 1 (Cycle 2)
measure: Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 0.24 mg/kg
timeFrame: Baseline and Day 1 (Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13,14, 15)
measure: Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 0.48 mg/kg
timeFrame: Baseline and Day 1 (Cycle 2, 3, 5, 6, 7, 8)
measure: Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 0.96 mg/kg
timeFrame: Baseline and Day 1 (Cycle 2, 3, 4, 5, 6)
measure: Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 1.92 mg/kg
timeFrame: Baseline and Day 1 (Cycle 2, 3, 4, 5, 6, 7, 8, 11, 12, 13, 14, 16)
measure: Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 2.50 mg/kg
timeFrame: Baseline and Day 1 (Cycle 2, 3, 4, 5, 6, 7, 8, 10, 12, 13, 14, 15, 16)
measure: Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 3.40 mg/kg and 4.60 mg/kg
timeFrame: Baseline and Day 1 (Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)
measure: Change From Baseline in Urine Protein Excretion (24 Hour)-Part 2 (MM)
timeFrame: Baseline and Day 1 (Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)
measure: Change From Baseline in Urine Protein Excretion (24 Hour)-Part 2 (NHL)
timeFrame: Baseline and Day 1 (Cycle 2)
Secondary outcomes:
measure: Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC[0-infinity]) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM- Part 1
timeFrame: Pre-dose, 30 minutes post start of infusion (SOI), at end of infusion (EOI), 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)
measure: AUC[0-infinity] of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM- Part 1: GSK2857916 2.50 mg/kg
timeFrame: Pre-dose and EOI of Day 1 (Cycle 1)
measure: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM- Part 1
timeFrame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)
measure: AUC[0-tau] of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM- Part 1: GSK2857916 2.50 mg/kg
timeFrame: Pre-dose and EOI of Day 1 (Cycle 1)
measure: Area Under the Concentration-time Curve From Zero to Time of Last Quantifiable Concentration (AUC[0-tlast]) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM- Part 1
timeFrame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)
measure: AUC[0-tlast]) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM- Part 1: GSK2857916 2.50 mg/kg
timeFrame: Pre-dose and EOI of Day 1 (Cycle 1)
measure: Clearance (CL) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1
timeFrame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)
measure: CL of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1: GSK2857916 2.50 mg/kg
timeFrame: Pre-dose and EOI of Day 1 (Cycle 1)
measure: Maximum Observed Concentration (Cmax) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1
timeFrame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)
measure: Cmax of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1: GSK2857916 2.50 mg/kg
timeFrame: Pre-dose and EOI of Day 1 (Cycle 1)
measure: Trough Plasma Concentration (Ctrough) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1
timeFrame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1), Pre-dose and EOI of Day 1 (Cycle 2 and Cycle 4)
measure: Ctrough of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1: GSK2857916 2.50 mg/kg
timeFrame: Pre-dose and EOI of Day 1 (Cycle 1, Cycle 2 and Cycle 4)
measure: Terminal Half-life (t1/2) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1
timeFrame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)
measure: t1/2 of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1: GSK2857916 2.50 mg/kg
timeFrame: Pre-dose and EOI of Day 1 (Cycle 1)
measure: Volume of Distribution at Steady State (Vss) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1
timeFrame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)
measure: Vss of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1: GSK2857916 2.50 mg/kg
timeFrame: Pre-dose and EOI of Day 1 (Cycle 1)
measure: Time to Reach Maximum Observed Concentration (Tmax) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1
timeFrame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)
measure: Tmax of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1: GSK2857916 2.50 mg/kg
timeFrame: Pre-dose and EOI of Day 1 (Cycle 1)
measure: Ctrough of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM-Part 2
timeFrame: Pre-dose and EOI of Day 1 (Cycle 1, Cycle 2 and Cycle 4)
measure: Ctrough of GSK2857916 Following IV Dose in Participants With NHL-Part 2
timeFrame: Pre-dose and EOI of Day 1 (Cycle 1, Cycle 2 and Cycle 3)
measure: AUC(0-tlast) of Cys Monomethyl Auristatin F (Cys-mcMMAF) Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM- Part 1
timeFrame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)
measure: AUC(0-tlast) of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM- Part 1: GSK2857916 2.50 mg/kg
timeFrame: Pre-dose and EOI of Day 1 (Cycle 1)
measure: Cmax of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM- Part 1
timeFrame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)
measure: Cmax of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM- Part 1: GSK2857916 2.50 mg/kg
timeFrame: Pre-dose and EOI of Day 1 (Cycle 1)
measure: Ctrough of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM- Part 1
timeFrame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1), Pre-dose and EOI of Day 1 (Cycle 2 and Cycle 4)
measure: Ctrough of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM- Part 1: GSK2857916 2.50 mg/kg
timeFrame: Pre-dose and EOI of Day 1 (Cycle 1, Cycle 2 and Cycle 4)
measure: Tmax of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM- Part 1
timeFrame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)
measure: Tmax of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM-Part 1: GSK2857916 2.50 mg/kg
timeFrame: Pre-dose and EOI of Day 1 (Cycle 1)
measure: Number of Participants With at Least One Confirmed Positive Post-Baseline Anti-drug Antibody Result- Part 1
timeFrame: Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With at Least One Confirmed Positive Post-Baseline Anti-drug Antibody Result- Part 2 (MM)
timeFrame: Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With at Least One Confirmed Positive Post-Baseline Anti-drug Antibody Result- Part 2 (NHL)
timeFrame: Up to 7.2 months (maximum duration of follow-up from first dose to last contact or death)
measure: Number of Participants With Antibodies to GSK2857916 in Serum Over Time- Part 1
timeFrame: Baseline, Day 1 (Cycle 2, 3, 4, 6, 9, 12, 16), End of study (within 30 days [+ 7 days of last treatment or prior to the start of new anti-cancer treatment], whichever is earlier) (1 cycle=21 days)
measure: Number of Participants With Antibodies to GSK2857916 in Serum Over Time- Part 2 (MM)
timeFrame: Baseline, Day 1 (Cycle 2, 3, 6, 7, 9, 11, 12, 16), End of study (within 30 days [+ 7 days of last treatment or prior to the start of new anti-cancer treatment], whichever is earlier) (1 cycle=21 days)
measure: Number of Participants With Antibodies to GSK2857916 in Serum Over Time - Part 2 (NHL)
timeFrame: Baseline, Day 1 (Cycle 2, 3), End of study (within 30 days [+ 7 days of last treatment or prior to the start of new anti-cancer treatment], whichever is earlier) (1 cycle=21 days)
measure: Overall Response Rate (ORR)- Part 1
timeFrame: From the Start of Treatment (at First Dose) up to the earlier of disease progression or the start of new anti-cancer therapy (maximum duration of follow-up is 21.6 months)
measure: ORR-Part 2 (MM)
timeFrame: From the Start of Treatment (at First Dose) up to the earlier of disease progression or the start of new anti-cancer therapy (maximum duration of follow-up is 24.2 months)
measure: ORR-Part 2 (NHL)
timeFrame: From the Start of Treatment (at First Dose) up to the earlier of disease progression or the start of new anti-cancer therapy (maximum duration of follow-up is 7.2 months)
measure: Clinical Benefit Rate (CBR)- Part 1
timeFrame: From the Start of Treatment (at First Dose) up to the earlier of disease progression or the start of new anti-cancer therapy (maximum duration of follow-up is 21.6 months)
measure: CBR- Part 2
timeFrame: From the Start of Treatment (at First Dose) up to the earlier of disease progression or the start of new anti-cancer therapy (maximum duration of follow-up is 24.2 months)
Other outcomes:
Locations:
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Vancouver
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Trudel S, Lendvai N, Popat R, Voorhees PM, Reeves B, Libby EN, Richardson PG, Hoos A, Gupta I, Bragulat V, He Z, Opalinska JB, Cohen AD. Antibody-drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy from dose expansion phase I study. Blood Cancer J. 2019 Mar 20;9(4):37. doi: 10.1038/s41408-019-0196-6.
citation: Trudel S, Lendvai N, Popat R, Voorhees PM, Reeves B, Libby EN, Richardson PG, Anderson LD Jr, Sutherland HJ, Yong K, Hoos A, Gorczyca MM, Lahiri S, He Z, Austin DJ, Opalinska JB, Cohen AD. Targeting B-cell maturation antigen with GSK2857916 antibody-drug conjugate in relapsed or refractory multiple myeloma (BMA117159): a dose escalation and expansion phase 1 trial. Lancet Oncol. 2018 Dec;19(12):1641-1653. doi: 10.1016/S1470-2045(18)30576-X. Epub 2018 Nov 12.
citation: Tai YT, Anderson KC. Targeting B-cell maturation antigen in multiple myeloma. Immunotherapy. 2015;7(11):1187-99. doi: 10.2217/imt.15.77. Epub 2015 Sep 15.