NCT04246047进行中（未招募）3 期
DREAMM 7: A Multicenter, Open-Label, Randomized Phase III Study to Evaluate the Efficacy and Safety of the Combination of Belantamab Mafodotin, Bortezomib, and Dexamethasone (B-Vd) Compared With the Combination of Daratumumab, Bortezomib and Dexamethasone (D-Vd) in Participants With Relapsed/Refractory Multiple Myeloma
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
- 494
- 试验地点
- 1
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
This is a Phase 3, randomized, open-label study designed to evaluate safety and efficacy of belantamab mafodotin in combination with bortezomib/dexamethasone (Arm A) versus daratumumab in combination with bortezomib/dexamethasone (Arm B) in the participants with relapsed recurrent multiple myeloma.
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
- •Confirmed diagnosis of multiple myeloma as defined by the International Myeloma Working Group (IMWG) criteria.
- •Previously treated with at least 1 prior line of multiple myeloma (MM) therapy, and must have documented disease progression during or after their most recent therapy.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Must have at least 1 aspect of measurable disease, defined as one of the following;
- •Urine M-protein excretion >=200 mg per 24-hour, or
- •Serum M-protein concentration >=0.5 grams per deciliter (g/dL), or
- •Serum free light chain (FLC) assay: involved FLC level >=10 mg per dL (>=100 mg per liter) and an abnormal serum free light chain ratio (<0.26 or >1.65).
- •All prior treatment-related toxicities (defined by National Cancer Institute Common Toxicity Criteria for Adverse Events [NCI-CTCAE] version 5.0) must be <=Grade 1 at the time of enrollment, except for alopecia.
- •Adequate organ function
排除标准
- •Intolerant to daratumumab.
- •Refractory to daratumumab or any other anti-CD38 therapy (defined as progressive disease during treatment with anti-CD38 therapy, or within 60 days of completing that treatment).
- •Intolerant to bortezomib, or refractory to bortezomib (defined as progressive disease during treatment with a bortezomib-containing regimen of 1.3 mg/m^2 twice weekly, or within 60 days of completing that treatment). Note: participants with progressive disease during treatment with a weekly bortezomib regimen are allowed.
- •Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain.
- •Prior treatment with anti-B-cell maturation antigen (anti-BCMA) therapy.
- •Prior allogenic stem cell transplant.
- •Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions, including renal, liver, cardiovascular, or certain prior malignancies.
- •Corneal epithelial disease.
研究组 & 干预措施
Belantamab mafodotin and Bortezomib plus Dexamethasone (Arm A)
Experimental
干预措施: Bortezomib (Drug)
Belantamab mafodotin and Bortezomib plus Dexamethasone (Arm A)
Experimental
干预措施: Belantamab mafodotin (Drug)
Belantamab mafodotin and Bortezomib plus Dexamethasone (Arm A)
Experimental
干预措施: Dexamethasone (Drug)
Daratumumab and Bortezomib plus Dexamethasone (Arm B)
Active Comparator
干预措施: Daratumumab (Drug)
Daratumumab and Bortezomib plus Dexamethasone (Arm B)
Active Comparator
干预措施: Bortezomib (Drug)
Daratumumab and Bortezomib plus Dexamethasone (Arm B)
Active Comparator
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: Up to approximately 41 months
PFS is defined as time from randomization until earliest date of disease progression (PD), determined by Independent Review Committee (IRC), according to the International Myeloma Working Group (IMWG) Response Criteria, or death due to any cause. PD= increase of \>=25% from lowest value in \>=1 of following (serum M-protein \[absolute increase \>=0.5 grams per deciliter {g/dL}\]; serum M-protein increase \>=1g/dL \[when lowest M-protein \>=5g/dL\]; urine M-protein \[absolute increase \>=200 milligrams per 24 hours {mg/24h}\]; participants without measurable serum \& urine M-protein levels, difference between involved \& uninvolved serum free light chains (sFLC) levels \[absolute increase \>10mg/dL\]; appearance of new lesion,\>=50% increase from nadir in Sum of the products of the maximal perpendicular diameters of measured lesions (SPD) of \>1 lesion, or \>=50% increase in longest diameter of previous lesion \>1 centimeter (cm) in short axis.
次要结局
- Clinical Benefit Rate (CBR)(Up to 73 months)
- Complete Response Rate (CRR)(Up to 73 months)
- Overall Response Rate (ORR)(Up to 73 months)
- Duration of Response (DoR)(Up to 73 months)
- Time to Response (TTR)(Up to 73 months)
- Time to Progression (TTP)(Up to 73 months)
- Overall Survival (OS)(Up to 73 months)
- Progression-free Survival on Subsequent Line of Therapy (PFS2)(Up to 73 months)
- Minimal Residual Disease (MRD) Negativity Rate(Up to 73 months)
- Number of Participants With Adverse Events (AEs)(Up to 73 months)
- Number of Participants With Clinically Significant Changes in Hematology Parameters(Up to 73 months)
- Number of Participants With Clinically Significant Changes in Clinical Chemistry(Up to 73 months)
- Number of Participants With Clinically Significant Changes in Urine Dipstick(Up to 73 months)
- Number of Participants With Abnormal Ocular Findings on Ophthalmic Examination(Up to 73 months)
- Plasma Concentrations of Belantamab Mafodotin (Total Antibody) at Indicated Time Points(Up to 73 months)
- Plasma Concentrations of Belantamab Mafodotin (ADC) at Indicated Time Points(Up to 73 months)
- Plasma Concentrations of Monomethyl Auristatin-F With a Cysteine Linker (Cys-mcMMAF) at Indicated Time Points(Up to 73 months)
- Number of Participants With Positive Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin(Up to 73 months)
- Titers of ADAs Against Belantamab Mafodotin(Up to 73 months)
- Number of Participants With Maximum Post-baseline Change From Baseline in Individual Items of Patient-Reported Outcome Version of the Common Term Criteria for Adverse Events (PRO-CTCAE)(Up to 73 months)
- Change From Baseline in Health Related Quality of Life (HRQoL) as Measured by EuropeanOrganization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ-C30)(Up to 73 months)
- Change From Baseline in HRQoL as Measured by EORTC IL52(Up to 73 months)
研究者
研究点 (1)
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相关资讯
FDA Raises Eye Safety Concerns for GSK's Blenrep Ahead of Advisory Committee Review- The FDA has identified significant ocular toxicity concerns with GSK's Blenrep (belantamab mafodotin) ahead of a July 17 advisory committee meeting to review the drug's reintroduction to the U.S. market.
- Clinical trials DREAMM-7 and DREAMM-8 showed that 92-93% of patients experienced keratopathy and visual acuity events, with 77-78% experiencing serious grade 3-4 events.
- GSK withdrew Blenrep from the U.S. market in 2022 after confirmatory trial shortcomings, despite initial FDA approval in 2020 for multiple myeloma treatment.
- The company's stock fell 1.19% following the FDA briefing document release, as eye safety concerns represent a unique toxicity profile among multiple myeloma therapies.last yearGSK Seeks FDA Approval for Blenrep Combination Therapy in Multiple Myeloma- GSK's Blenrep, previously withdrawn, aims for re-approval as a combination therapy for multiple myeloma after at least one prior line of treatment.
- The FDA has accepted GSK's application for Blenrep combined with bortezomib plus dexamethasone, or pomalidomide plus dexamethasone, with a decision expected by July 2025.
- Phase III trials DREAMM-7 and DREAMM-8 demonstrated statistically significant improvements in progression-free survival compared to standard-of-care regimens.
- Blenrep's potential approval could introduce competition to BCMA-targeted therapies, offering a simpler administration route than CAR-T therapy.last yearGSK Seeks FDA Approval for Blenrep Combination Therapy in Multiple Myeloma- GSK's Blenrep, previously withdrawn, seeks FDA approval in combination with Velcade and dexamethasone for multiple myeloma patients after one prior therapy.
- The application is based on DREAMM-7 and DREAMM-8 Phase III trials, demonstrating statistically significant improvements in progression-free survival.
- Blenrep's combination offers a potential advantage over CAR-T therapy due to its off-the-shelf nature and simpler administration.
- GlobalData forecasts Blenrep to generate $1.4 billion in 2030, offering new competition in the BCMA-targeted therapy landscape.last yearBlenrep Demonstrates Overall Survival Benefit in Relapsed/Refractory Multiple Myeloma- The DREAMM-7 phase III trial showed Blenrep (belantamab mafodotin) plus bortezomib and dexamethasone (BorDex) significantly reduced the risk of death in relapsed/refractory multiple myeloma patients.
- The Blenrep combination demonstrated a statistically significant 42% decrease in the risk of death compared to daratumumab plus BorDex (HR 0.58; 95% CI: 0.43-0.79; p=0.00023).
- Median overall survival was estimated at 84 months for the Blenrep cohort versus 51 months for the daratumumab cohort, with a three-year overall survival rate of 74% and 60%, respectively.
- Blenrep plus BorDex also showed statistically significant superiority in minimal residual disease negativity and clinically meaningful improvements in duration of response and progression-free survival.last yearBelantamab Mafodotin Triplet Demonstrates Improved Overall Survival in Relapsed/Refractory Multiple Myeloma- The DREAMM-7 phase 3 trial showed that belantamab mafodotin, bortezomib, and dexamethasone (BVd) significantly improved overall survival in relapsed/refractory multiple myeloma patients.
- BVd demonstrated a 42% reduction in the risk of death compared to daratumumab, bortezomib, and dexamethasone (DVd), with a projected median OS of 84 months versus 51 months.
- The belantamab mafodotin combination also achieved statistically significant superiority in minimal residual disease (MRD) negativity compared to the daratumumab combination.
- Regulatory filings for belantamab mafodotin combinations have been accepted in multiple major markets, potentially establishing a new standard of care.last year
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