NCT04162210进行中（未招募）3 期
A Phase III, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Single Agent Belantamab Mafodotin Compared to Pomalidomide Plus Lowdose Dexamethasone (Pom/Dex) in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) (DREAMM 3)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 325
- 试验地点
- 136
- 主要终点
- Progression-free Survival (PFS) Based on Investigator-assessed Response as Per International Myeloma Working Group (IMWG)
研究概览
简要总结
This open-label, randomized study for evaluating the efficacy and safety of single agent belantamab mafodotin when compared to pom/dex in participants with RRMM. Participants will be randomized in a 2:1 ratio to receive either single agent belantamab mafodotin or pom/dex. Belantamab mafodotin will be administered on Day 1 (D1) at every 3 weeks (Q3W) schedule. Pomalidomide will be administered daily on Days 1 to 21 of each 28-day cycle, with dexamethasone administered once weekly (Days 1, 8, 15, and 22). Participants in both arms will be treated until disease progression, death, unacceptable toxicity, withdrawal of consent, and lost to follow-up or end of study, whichever comes 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
- •Capable of giving signed informed consent.
- •Participants must be 18 or older, at the time of signing the informed consent. In Republic of Korea, participants must be over 19 years of age inclusive, at the time of signing informed consent.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Histologically or cytologically confirmed diagnosis of Multiple myeloma (MM) as defined according to IMWG, and : Has undergone autologous stem cell transplant (SCT), or is considered transplant ineligible; Has received at least 2 prior lines of anti-myeloma treatments, including at least 2 consecutive cycles of both lenalidomide and a proteasome inhibitor (given separately or in combination), and must have documented disease progression on, or within 60 days of, completion of the last treatment or must be non-responsive while on last treatment, where non-responsive is defined as not achieving at least Minimal Response (MR) after 2 complete treatment cycles. In such cases lack of achieving of at least MR must be determined no earlier than at least 4 weeks after the last treatment.
- •Has measurable disease with at least one of the following: Serum M-protein >=0.5 gram per deciliter (g/dL) (>=5 gram per Liter); Urine M-protein >=200 mg/24 hours; Serum free light chain (FLC) assay: Involved FLC level >=10 milligram per deciliter (mg/dL) (>=100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65).
- •Participants with a history of autologous SCT are eligible for study participation provided the following eligibility criteria are met: Transplant was >100 days prior to initiating study treatment; No active infection(s).
- •Adequate organ system functions as defined: Absolute neutrophil count (ANC) >=1.0*10^9/L; Hemoglobin >= 8.0 g/dL; Platelets >= 50x10^9/L; Total bilirubin <=1.5* Upper limit of normal (ULN) (isolated bilirubin >1.5*ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent); ALT <=2.5*ULN; Estimated glomerular filtration rate (eGFR) >=30 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2); Spot urine (albumin/creatinine ratios) <=500 milligram per gram (mg/g) (56 milligram per millimoles [mg/mmol]).
- •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 until 6 months after the last dose of study intervention to allow for clearance of any altered sperm: 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 contraception/barrier as detailed below depending on whether they are randomised to Arm 1 (belantamab mafodotin) or Arm 2 (pom/dex), even if they have undergone a successful vasectomy: Agree to use a male condom throughout study treatment including the 6 month follow-up period even if they have undergone a successful vasectomy and a female partner to use an additional highly effective contraceptive method with a failure rate of <1 percent per year when having sexual intercourse with a pregnant woman or a woman of childbearing potential who is not currently pregnant. Four weeks for male participants on Treatment Arm 2 (pom/dex).
- •A female participant 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 agrees to abide by the following: Arm 1 (belantamab mafodotin): Use a contraceptive method that is highly effective (with a failure rate of <1 percent per year) which includes abstinence, preferably with low user dependency during the intervention period and for 4 months after the last dose of study treatment. Arm 2 (pom/dex): Due to pomalidomide being a thalidomide analogue with risk for embryofetal toxicity and prescribed under a pregnancy prevention/controlled distribution program, WOCBP participants will be eligible if they commit either to abstain continuously from heterosexual sexual intercourse or to use two methods of reliable birth control (one method that is highly effective), beginning 4 weeks prior to initiating treatment with pomalidomide, during therapy, during dose interruptions and continuing for at least 4 weeks following discontinuation of pomalidomide treatment. Two negative pregnancy tests must be obtained prior to initiating therapy. The first test should be performed within 10-14 days and the second test within 24 hours prior to prescribing pomalidomide therapy. And agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should confirm the effectiveness of the contraceptive method(s) ahead of the first dose of study intervention.
- •All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events [NCI-CTCAE], version 5.0, 2017) must be <=Grade 1 at the time of enrollment, except for alopecia and Grade 2 peripheral neuropathy.
排除标准
- •Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes); active plasma cell leukemia at the time of screening.
- •Systemic anti-myeloma therapy or use of an investigational drug within <14 days or 5 half-lives, whichever is shorter, before the first dose of study intervention.
- •Prior treatment with an anti-MM monoclonal antibody within 30 days prior to receiving the first dose of study intervention.
- •Prior B cell maturation antigen (BCMA)-targeted therapy or prior pomalidomide treatment.
- •Plasmapheresis within 7 days prior to the first dose of study intervention.
- •Prior allogeneic stem cell transplant. (Participants who have undergone syngeneic transplant will be allowed only if no history of, or currently active, Graft-Versus-Host Disease [GvHD]).
- •Any major surgery within the last 4 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, provided they fulfil criteria as described in inclusion criteria.
- •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 with study procedures.
- •History of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
- •Evidence of active mucosal or internal bleeding.
- •Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. (Stable chronic liver disease [including Gilbert's syndrome or asymptomatic gallstones] or hepatobiliary involvement of malignancy is acceptable if participant otherwise meets entry criteria)
- •Participants with previous or concurrent malignancies other than multiple myeloma are excluded, unless the second malignancy has been considered medically stable for at least 2 years. The participant must not be receiving active therapy, other than hormonal therapy for this disease. (Participants with curatively treated non-melanoma skin cancer are allowed without a 2-year restriction).
- •Evidence of cardiovascular risk including any of the following: Evidence of current clinically significant uncontrolled arrhythmias including clinically significant electrocardiogram (ECG) abnormalities including 2nd degree (Mobitz Type II) or 3rd degree atrioventricular block; History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening; Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; Uncontrolled hypertension.
- •Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to belantamab mafodotin, pomalidomide, dexamethasone or any of the components of the study intervention.
- •Pregnant or lactating female.
- •Active infection requiring treatment.
- •Known human immunodeficiency virus (HIV), unless the participant can meet all of the following criteria: Established anti-retroviral therapy (ART) for at least 4 weeks and HIV viral load <400 copies/mL; CD4+ T-cell (CD4+) counts ≥350 cells/uL; No history of AIDS-defining opportunistic infections within the last 12 months.(Consideration must be given to ART and prophylactic antimicrobials that may have a drug-drug interaction and/or overlapping toxicities with belantamab mafodotin or other combination products as relevant)
- •Participants with Hepatitis B will be excluded unless the following criteria can be met: If the participant is hepatitis B core antibody (HbcAb) positive or hepatitis B surface antigen (HbsAg) negative, then hepatitis B virus (HBV) deoxyribonucleic acid (DNA) should be undectectable at the time of screening; If HbsAg+ at screening or <=3 months prior to first dose of study treatment, then HBV DNA should be undetectable, highly effective antiviral treatment should be started ≥4 weeks prior to first dose of study treatment, exclusion of participants with cirrhosis and participants in Japan must test hepatitis B e antigen (HBeAg) and hepatitis B e antibody (HBeAb ).
- •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 unless the participant can meet the following criteria: Hepatitis C RNA test negative at Screening and successful anti-viral treatment (usually 8 weeks duration) is required, followed by a negative HCV RNA test after a washout period of at least 4 weeks (Hepatitis RNA is optional and participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing).
- •Participants unable to tolerate thromboembolic prophylaxis.
- •Current corneal epithelial disease except for mild punctate keratopathy.
研究组 & 干预措施
Participants receiving pom/dex
Active Comparator
Participants will receive pomalidomide daily on Days 1 to 21 of each 28-day cycle, with dexamethasone once weekly on Days 1, 8, 15 and 22.
干预措施: Pom/dex (Pomalidomide plus low dose Dexamethasone) (Drug)
Participants receiving Belantamab mafodotin
Experimental
Participants will receive belantamab mafodotin single agent dose on Day 1 of Q3W
干预措施: Belantamab mafodotin (Drug)
结局指标
主要结局
Progression-free Survival (PFS) Based on Investigator-assessed Response as Per International Myeloma Working Group (IMWG)
时间窗: Up to 27 months
PFS is time from randomization until earliest date of progressive disease (PD), or death due to any cause per investigator-assessed response per IMWG. PD is ≥25% increase from nadir in any of following: serum M-protein (absolute increase ≥0.5 gram per deciliter \[g/dL\]),urine M-protein(absolute increase ≥200 mg/24hr),difference between involved/uninvolved FLC levels (absolute increase \>10 mg/dL) in patients without measurable serum and urine M-protein levels, or bone marrow plasma-cell percentage irrespective of baseline status (absolute increase ≥10%) in patients without measurable serum and urine M-protein levels and without measurable involved FLC levels; appearance of new lesion,≥50% increase in longest diameter of a lesion previously measured \>1cm in short axis, or ≥50% increase from nadir in sum of products of two longest perpendicular diameters of more than 1 lesion; ≥50% increase in circulating plasma cells (minimum of 200 cells/microliter) if this is only measure of disease.
Progression-Free Survival (PFS) Based on Investigator-Assessed Response as Per International Myeloma Working Group (IMWG)
时间窗: Up to 27 months
PFS is time from randomization until earliest date of progressive disease (PD), or death due to any cause per investigator-assessed response per IMWG. PD is ≥25% increase from nadir in any of following: serum M-protein (absolute increase ≥0.5 gram per deciliter \[g/dL\]),urine M-protein(absolute increase ≥200 mg/24hr),difference between involved/uninvolved FLC levels (absolute increase \>10 mg/dL) in patients without measurable serum and urine M-protein levels, or bone marrow plasma-cell percentage irrespective of baseline status (absolute increase ≥10%) in patients without measurable serum and urine M-protein levels and without measurable involved FLC levels; appearance of new lesion,≥50% increase in longest diameter of a lesion previously measured \>1cm in short axis, or ≥50% increase from nadir in sum of products of two longest perpendicular diameters of more than 1 lesion; ≥50% increase in circulating plasma cells (minimum of 200 cells/microliter) if this is only measure of disease.
次要结局
- Overall Survival (OS)(60 months)
- Time to Progression (TTP)(Up to 55 months)
- Clinical Benefit Rate (CBR)(Up to 55 months)
- Change From Baseline in Hematology Parameters: Mean Corpuscular Hemoglobin (MCH) [Picograms](Baseline and up to 55 months)
- Change From Baseline in Urinalysis Parameter: Glucose (Millimole Per Liter)(Baseline and up to 55 months)
- Change From Baseline in Urinalysis Parameter: Protein (Grams Per Liter)(Baseline and up to 55 months)
- Rate of Minimal Residual Disease (MRD)(Up to 55 months)
- Duration of Response (DoR)(Up to 55 months)
- Time to Response (TTR)(Up to 55 months)
- Change From Baseline in Hematology Parameters: Hematocrit (Proportion of Red Blood Cells in Blood)(Baseline and up to 55 months)
- Change From Baseline in Clinical Chemistry Parameters: Albumin and Total Protein (Grams Per Liter)(Baseline and up to 55 months)
- Change From Baseline in Urinalysis Parameter: Specific Gravity (Ratio)(Baseline and up to 55 months)
- Change From Baseline in Urinalysis Parameter: Ketones (Millimoles Per Liter)(Baseline and up to 55 months)
- Change From Baseline in Urinalysis Parameter: Creatinine/Albumin Ratio (Ratio)(Baseline and up to 55 months)
- Plasma Concentrations of Belantamab Mafodotin(Up to 55 months)
- Number of Participants With Symptomatic Adverse Effects Measured by Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)(Up to 55 months)
- Overall Response Rate (ORR)(Up to 55 months)
- Number of Participants With Adverse Events (AEs)(Up to 55 months)
- Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count and Reticulocyte Count (Trillion Cells Per Liter)(Baseline and up to 55 months)
- Change From Baseline in Hematology Parameters: Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Grams Per Liter)(Baseline and up to 55 months)
- Change From Baseline in Hematology Parameters: Mean Corpuscular Volume (MCV) [Femtoliter](Baseline and up to 55 months)
- Change From Baseline in Clinical Chemistry Parameters: Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid (Micromoles Per Liter)(Baseline and up to 55 months)
- Change From Baseline in Urinalysis Parameters- Urine Potential of Hydrogen (pH) (Points on a Scale)(Baseline and up to 55 months)
- Number of Participants With Anti-drug Antibody (ADAs) Against Belantamab Mafodotin(Up to 55 months)
- Change From Baseline in Clinical Chemistry Parameters: Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT), and Lactate Dehydrogenase (LDH)(Baseline and up to 55 months)
- Change From Baseline in Urinalysis Parameter: Blood (10^9 Cells Per Liter)(Baseline and up to 55 months)
- Number of Participants With Abnormal Ocular Findings(Up to 55 months)
- Plasma Concentrations of Total Monoclonal Antibody (mAb)(Up to 55 months)
- Plasma Concentrations of Cys-mc Microtubular Inhibitor Monomethyl Auristatin-F (MMAF)(Up to 55 months)
- Change From Baseline in Hematology Parameters: Absolute White Blood Cell Count (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, and Neutrophils (Giga Cells Per Liter)(Baseline and up to 55 months)
- Change From Baseline in Clinical Chemistry Parameters: Calcium, Chloride, Glucose, Potassium, Sodium, Magnesium, Blood Urea Nitrogen (BUN), and Phosphorous (Millimoles Per Liter)(Baseline and up to 55 months)
- Titer of ADAs Against Belantamab Mafodotin(Up to 55 months)
- European Organization for Research and Treatment of Cancer IL52 (EORTC IL52) Score(Up to 55 months)
- Number of Participants With Symptomatic Adverse Effects Measured by Ocular Surface Disease Index (OSDI)(Up to 55 months)
- Overall Survival (OS)(Up to approximately 263 weeks)
- Overall Response Rate (ORR)(Up to approximately 263 weeks)
- Clinical Benefit Rate (CBR)(Up to approximately 263 weeks)
- Duration of Response (DoR)(Up to approximately 263 weeks)
- Time to Response (TTR)(Up to approximately 263 weeks)
- Time to Progression (TTP)(Up to approximately 263 weeks)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(Up to approximately 263 weeks)
- Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-baseline Relative to Baseline(Baseline (Day 1) and up to approximately 263 weeks)
- Number of Participants With Maximum Grade Increase Post-Baseline Relative to Baseline in Hematology(Baseline (Day 1) and up to approximately 263 weeks)
- Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-baseline Relative to Baseline(Baseline (Day 1) and up to approximately 263 weeks)
- Number of Participants With Maximum Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry(Baseline (Day 1) and Up to approximately 263 weeks)
- Number of Participants With Shift in Urine Albumin Creatinine Ratio From Baseline to Worst Post-Baseline(Baseline (Day 1) and Up to approximately 263 weeks)
- Number of Participants With Maximum Worst-case Change From Baseline in Best Corrected Visual Acuity Test (BCVA) Scores(Baseline (Day 1) and up to approximately 263 weeks)
- Observed Plasma Concentrations of Belantamab Mafodotin- Antibody-drug Conjugate (ADC)(Pre-dose on Day (D)1 of Cycles(C)1,2,3,4,6,9,12,18,24,30,36,42; End of Infusion (EOI) on D1 of C1,2,3,4&6; Start of infusion (SOI) + 2 hours(h) on D1,SOI + 24 h on D1; D4,D8-15,D22 of C1&C3; D1 of C2,3,4&6; C3D2; & End of Treatment(EOT) (~242 weeks))
- Observed Plasma Concentrations of Belantamab Mafodotin- Total Monoclonal Antibody (mAb)(Pre-dose on Day (D)1 of Cycles (C)1,2,3,4,6,9,12,18,24,30,36,42; EOI on D1 of C1,2,3, 4 & 6; SOI + 24h on D1&2 of C1&3; D4, D8-15, D22 of C1&3; D1of C2,3,4 & 6; D2 of C3; and EOT (~242 weeks))
- Observed Plasma Concentrations of Belantamab Mafodotin-Cys-mc Microtubular Inhibitor Monomethyl Auristatin-F (MMAF)(Pre-dose on Day (D)1 of Cycles (C)1,2,3,4,6,9,12,18,24,30,36,42; EOI on D1 of C1,2,3, 4 & 6; D1 SOI + 2 h of C1&3; D2 SOI + 24h of C1&3; D4, D8-15, D22 of C1&3; D1 of C2,3,4,6,9,12,18,24 & 30; D2 of C3; and EOT (~242 weeks))
- Number of Participants With Post-baseline Positive Anti-Drug Antibody (ADAs) Against Belantamab Mafodotin(Upto approximately 263 weeks)
- Titers of ADAs Against Belantamab Mafodotin(Up to approximately 263 weeks)
- Number of Participants With Symptomatic Adverse Effects as Measured by the Patient Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)(Up to approximately 263 weeks)
- Change From Baseline (CFB) in Ocular Surface Disease Index (OSDI) Total Score(Baseline (Day 1) and Up to approximately 263 weeks)
- Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ-C30) Score.(Baseline (Day 1), every three weeks(Q3W) starting from week 4 until week 238, End of Treatment (~242 weeks) and Follow up (~ 263 weeks))
- Change From Baseline (CFB) in EORTC QLQ 20-item Multiple Myeloma Module (MY20) Score(Baseline (Day 1), every three weeks(Q3W) starting from week 4 until week 238, End of Treatment (~242 weeks) and Follow up (~263 weeks))
- Change From Baseline (CFB) in EORTC IL52 Score(Baseline (Day 1), every three weeks(Q3W) starting from week 4 until week 238)
- Number of Participants With Minimal Residual Disease (MRD) Negativity Rate(Up to approximately 263 weeks)
研究者
研究点 (136)
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