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临床试验/NCT03525678
NCT03525678已完成2 期

A Phase II, Open Label, Randomized, Two-Arm Study to Investigate the Efficacy and Safety of Two Doses of the Antibody Drug Conjugate GSK2857916 in Participants With Multiple Myeloma Who Had 3 or More Prior Lines of Treatment, Are Refractory to a Proteasome Inhibitor and an Immunomodulatory Agent and Have Failed an Anti-CD38 Antibody (DREAMM 2)

GlaxoSmithKline1 个研究点 分布在 1 个国家目标入组 221 人开始时间: 2018年6月18日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
2 期
状态
已完成
入组人数
221
试验地点
1
主要终点
Overall Response Rate by Independent Review Committee (Efficacy Population)
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Multiple myeloma (MM) is an incurable malignancy and accounts for 1 percentage (%) of all cancers and for 10% of all hematologic malignancies. Participants with relapsed/refractory multiple myeloma (RRMM) will be included in this study, to evaluate the efficacy and safety of belantamab mafodotin (GSK2857916) monotherapy. Participants will be treated with belantamab mafodotin monotherapy until disease progression (PD) or unacceptable toxicity and will be followed for Progression Free Survival and Overall survival. The participants will be randomized to receive either frozen belantamab mafodotin at the dose of 2.5 milligram per kilogram (mg/kg) or 3.4 mg/kg administered Intravenously (IV). There will be an independent cohort of participants who will receive a lyophilized configuration of belantamab mafodotin. For participants who discontinued from the study other than Progressive disease (PD), disease evaluation will continue to be performed at 3-week intervals until confirmed PD, death, start of a new anticancer treatment, withdrawal of consent, or end of the study whichever occurs first.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Treatment
盲法
None

入排标准

年龄范围
18 Years 至 —（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Participants who provided signed written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • •Male or female, 18 years or older.
  • •Participants with Eastern Cooperative Oncology Group (ECOG) performance status of 0-
  • •Participants with histologically or cytologically confirmed diagnosis of MM as defined in IMWG, 2014 criteria, and participant has undergone stem cell transplant or is considered transplant ineligible and has failed at least 3 prior lines of anti-myeloma treatments, including an anti-CD38 antibody (example [e.g.], daratumumab) alone or in combination, and is refractory to an Immunomodulatory drug (IMiD) (that is [i.e.], lenalidomide or pomalidomide), and to a proteasome inhibitor (e.g., bortezomib, ixazomib or carfilzomib).
  • •The participant has measurable disease with at least one of the following: Serum M-protein >=0.5 grams per deciliter (g/dL) (>=5 grams per Liter [g/L]); Urine M-protein >=200 milligram per 24 hours (mg/24h); Serum Free light chain (FLC) assay: Involved FLC level >=10 mg/dL (>=100 mg/Liter) and an abnormal serum FLC ratio (<0.26 or >1.65).
  • •Participants 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 enrollment; no active infection(s); participants meet the remainder of the eligibility criteria outlined in the protocol.
  • •Participants with adequate organ system functions as defined follows: Absolute neutrophil count (ANC) >=1.0 X 10^9/L; Hemoglobin >=8.0 g/dL; Platelets>= 50 X 10^9/L; Total bilirubin <=1.5X Upper limit of normal (ULN). Isolated bilirubin >=1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent); Alanine aminotransferase (ALT) <=2.5X ULN; Estimated glomerular filtration rate (eGFR) >=30 milliliter per minute per 1.73 meter square (mL/min/m^2); Spot urine (albumin/creatinine ratios [spot urine]) <500 milligram per gram (mg/g) (56 mg per millimoles [mg/mmol]); Left ventricular ejection fraction (LVEF) (Echocardiogram)>=45 percent.
  • •Female participants: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female participant is eligible to participate if she is not pregnant or breastfeeding, and 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 80 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 participants: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 140 days: Refrain from donating sperm; 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 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 as when having sexual intercourse with a WOCBP who is not currently pregnant.
  • •All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events [NCI-CTCAE]), version 4.03, must be <=Grade 1 at the time of enrollment except for alopecia and Grade 2 peripheral neuropathy.
  • •For France only: A participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

排除标准

  • •Systemic anti-myeloma therapy within <=14 days, or 5 half-lives, whichever is shorter, or plasmapheresis within 7 days prior to the first dose of study drug.
  • •Systemic treatment with high dose steroids (equivalent to >=60 mg prednisone daily for >=4 days) within the past 14 days if administered to treat MM or non-MM disease.
  • •Symptomatic amyloidosis, active 'polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes' (POEMS) syndrome, active plasma cell leukemia at the time of screening.
  • •Prior allogeneic stem cell transplant.
  • •Current corneal epithelial disease except mild punctate keratopathy.
  • •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 drugs. Prior B-cell maturation antigen (BCMA) targeted therapy.
  • •Evidence of active mucosal or internal bleeding.
  • •Any major surgery within the last four weeks.
  • •Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant's safety). Participants with isolated proteinuria resulting from MM are eligible.
  • •Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures.
  • •Current unstable 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 participant has been disease-free for more than 2 years and, in the opinion of the principal investigators and GlaxoSmithKline Medical Monitor, will not affect the evaluation of the effects of this clinical trial treatment on the currently targeted malignancy (MM). Participants with curatively treated non-melanoma skin cancer may be enrolled.
  • •Evidence of cardiovascular risk including any of the following: Corrected QT interval Fridericia (QTcF) interval >480 milliseconds (msec); Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant electrocardiogram abnormalities such as 2nd degree (Type II) or 3rd degree atrioventricular (AV) block; 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 (NYHA); Uncontrolled hypertension.
  • •Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to belantamab mafodotin, or any of the components of the study treatment.
  • •Pregnant or lactating female.
  • •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.

研究组 & 干预措施

Participants receiving frozen 2.5 mg/kg belantamab mafodotin

Experimental

Participants will receive 2.5 mg/kg frozen liquid belantamab mafodotin. Participants will be administered with frozen liquid belantamab mafodotin via infusion pump every 3 weeks.

干预措施: Belantamab mafodotin frozen liquid (Drug)

Participants receiving frozen 3.4 mg/kg belantamab mafodotin

Experimental

Participants will receive 3.4 mg/kg frozen liquid belantamab mafodotin. Participants will be administered with frozen liquid belantamab mafodotin via infusion pump every 3 weeks.

干预措施: Belantamab mafodotin frozen liquid (Drug)

Participants receiving lyophilized belantamab mafodotin

Experimental

Participants in lyophilized arm will receive lyophilized belantamab mafodotin once lyophilized configuration becomes available and enrollment has been completed for frozen liquid arms.

干预措施: Belantamab mafodotin lyophilized powder (Drug)

结局指标

主要结局

Overall Response Rate by Independent Review Committee (Efficacy Population)

时间窗: Up to 48 weeks

ORR was determined according to the 2016 IMWG response criteria by IRC. ORR was calculated as the percentage of participants with a confirmed PR or better (i.e., PR, VGPR, CR and sCR). Confidence intervals were based on the exact method. Efficacy Population comprised of first 130 intent-to-treat participants whether or not randomized treatment (frozen solution) was administered. Intent-to-treat Population comprised of all randomized participants whether or not randomized treatment was administered.

Overall Response Rate (ORR) by Independent Review Committee (IRC) (Full Analysis Population)

时间窗: Up to 48 weeks

ORR was determined according to the 2016 international myeloma working group (IMWG) response criteria by IRC. ORR was calculated as the percentage of participants with a confirmed partial response (PR) or better (that is \[i.e.\], PR, very good partial response \[VGPR\], complete response \[CR\] and stringent complete response \[sCR\]). Confidence intervals were based on the exact method.

次要结局

  • Duration of Response (DoR) by Investigator Assessment (Full Analysis Population)(Up to 186 weeks)
  • Duration of Response by Independent Review Committee (Full Analysis Population)(Up to 186 weeks)
  • Time to Response by Investigator Assessment (Full Analysis Population)(Up to 186 weeks)
  • Overall Response Rate by Investigator Assessment (Efficacy Population)(Up to 186 weeks)
  • Clinical Benefit Rate by Independent Review Committee (Full Analysis Population)(Up to 186 weeks)
  • Clinical Benefit Rate by Independent Review Committee (Efficacy Population)(Up to 186 weeks)
  • Time to Response by Investigator Assessment (Efficacy Population)(Up to 186 weeks)
  • Duration of Response by Independent Review Committee (Efficacy Population)(Up to 186 weeks)
  • Time to Response by Independent Review Committee (Efficacy Population)(Up to 186 weeks)
  • Overall Response Rate by Investigator Assessment (IA) (Full Analysis Population)(Up to 186 weeks)
  • Duration of Response by Investigator Assessment (Efficacy Population)(Up to 186 weeks)
  • Time to Response by Independent Review Committee (Full Analysis Population)(Up to 186 weeks)
  • Progression Free Survival by Independent Review Committee(Up to 186 weeks)
  • Number of Participants With Abnormal Findings During Physical Examination(Up to 186 weeks)
  • Clinical Benefit Rate (CBR) by Investigator Assessment (Full Analysis Population)(Up to 186 weeks)
  • Clinical Benefit Rate by Investigator Assessment (Efficacy Population)(Up to 186 weeks)
  • Time to Progression by Independent Review Committee(Up to 186 weeks)
  • Number of Participants With Grade Change From Baseline in Hematology Parameters(Baseline (Day 1) and Up to 186 weeks)
  • Number of Participants With Change From Baseline in Pulse Rate(Baseline (Day 1) and Up to 186 weeks)
  • Number of Participants With Intraocular Pressure (IOP) >=22 mmHg Anytime Post-Baseline(Up to 186 weeks)
  • 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 RRMM(Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days))
  • AUC(0-tlast) of GSK2857916 Total Antibody Following IV Dose in Participants With RRMM(Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days))
  • Time to Progression by Investigator Assessment(Up to 186 weeks)
  • Number of Participants With Change From Baseline in Body Temperature(Baseline (Day 1) and Up to 186 weeks)
  • Number of Participants With Change From Baseline in Best Corrected Visual Acuity (BCVA) Test Scores(Baseline (Day 1) and Up to 186 weeks)
  • Number of Participants With Shift in Pupillary Examination Findings From Normal (Baseline) to Abnormal (Worst Post-Baseline)(Baseline and Up to 186 weeks)
  • Number of Participants With Shift in Corneal Epithelium Findings From Normal (Baseline) to Abnormal (Worst Post-Baseline) for Corneal Epithelium (CE) and Corneal Stroma (CS)(Baseline and Up to 186 weeks)
  • Number of Participants With Shift in Tear Break-up Time From >10 Seconds (Baseline) to <=5 Seconds (Worst Post-Baseline)(Baseline and Up to 186 weeks)
  • AUC(0-tau) of GSK2857916 Total Antibody Following IV Dose in Participants With RRMM(Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days))
  • Progression Free Survival by Investigator Assessment(Up to 186 weeks)
  • Overall Survival(Up to 186 weeks)
  • Number of Participants With Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)(Baseline (Day 1) and Up to 186 weeks)
  • Number of Participants With Serious Adverse Events (SAEs), Common (>=5%) Non-serious Adverse Events and Adverse Events of Special Interest (AESI)(Up to 186 weeks)
  • AUC(0-infinity) of GSK2857916 Total Antibody Following IV Dose in Participants With RRMM(Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days))
  • Number of Participants With Change From Baseline in Hematology Parameters With Respect to the Normal Range(Baseline (Day 1) and Up to 186 weeks)
  • Number of Participants With Change From Baseline in Clinical Chemistry Parameters With Respect to the Normal Range(Baseline (Day 1) and Up to 186 weeks)
  • Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters(Baseline (Day 1) and Up to 186 weeks)
  • Number of Participants With Shift in Extraocular Muscle Movement From Yes (Baseline) to no (Worst Post-Baseline)(Baseline and Up to 186 weeks)
  • Number of Participants With Shift in Corneal Epithelium Findings From no (Baseline) to Yes (Worst Post-Baseline)(Baseline and Up to 186 weeks)
  • Maximum Observed Concentration (Cmax) of GSK2857916 Following IV Dose in Participants With RRMM(Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days))
  • Time to Reach Maximum Observed Concentration (Tmax) of GSK2857916 Following IV Dose in Participants With RRMM(Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days))
  • Tmax of GSK2857916 Total Antibody Following IV Dose in Participants With RRMM(Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days))
  • Titers of Anti-drug Antibodies Against GSK2857916(Up to 186 weeks)
  • Number of Participants With Symptomatic AEs Measured by Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)(Up to 186 weeks)
  • Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC[0-infinity]) of GSK2857916 Following IV Dose in Participants With RRMM(Cycle 1 and Cycle 3: Pre-dose, end of infusion (EOI), 2 hours and 24 hours post start of infusion (SOI) on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days))
  • Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK2857916 Following IV Dose in Participants With RRMM(Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days))
  • Terminal Half-life (t1/2) of GSK2857916 Following IV Dose in Participants With RRMM(Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days))
  • Cmax of GSK2857916 Total Antibody Following IV Dose in Participants With RRMM(Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days))
  • Tmax of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With RRMM(Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days))
  • Change From Baseline in EORTC QLQ 20-item Multiple Myeloma Module (MY20) Score(Baseline (Day 1) and Week 07, Week 13, Week 19, Week 25, Week 31, Week 37, Week 43, Week 61, Week 79, Week 97, Week 115, Week 133, Week 151, Week 169, and Week 186)
  • t1/2 of GSK2857916 Total Antibody Following IV Dose in Participants With RRMM(Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days))
  • AUC(0-infinity) of Cysteine-maleimidocaproyl Monomethyl Auristatin F (Cys-mcMMAF) Following IV Dose of GSK2857916 in Participants With RRMM(Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days))
  • AUC(0-tau) of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With RRMM(Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days))
  • AUC(0-tlast) of Cysteine-maleimidocaproyl Monomethyl Auristatin F (Cys-mcMMAF) Following IV Dose of GSK2857916 in Participants With RRMM(Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days))
  • Number of Participants With at Least One Confirmed Positive Post-Baseline Anti-drug Antibody (ADA) Result(Up to 186 weeks)
  • Worst Change From Baseline in National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) Overall Composite Score(Baseline (Day 1) and up to Week 186)
  • Worst Change From Baseline in Ocular Surface Disease Index (OSDI) Total Score(Baseline (Day 1) and up to Week 186)
  • Cmax of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With RRMM(Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days))
  • Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ-C30) Score(Baseline (Day 1) and Week 07, Week 13, Week 19, Week 25, Week 31, Week 37, Week 43, Week 61, Week 79, Week 97, Week 115, Week 133, Week 151, Week 169, and Week 186)
  • t1/2 of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With RRMM(Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days))

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (1)

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