NCT04484623进行中（未招募）3 期
A Phase III, Multicenter, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin in Combination With Pomalidomide and Dexamethasone (B-Pd) Versus Pomalidomide Plus Bortezomib and Dexamethasone (PVd) in Participants With Relapsed/Refractory Multiple Myeloma (DREAMM 8)
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
- 302
- 试验地点
- 123
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This study will evaluate the efficacy and safety of belantamab mafodotin in combination with pomalidomide and dexamethasone (Arm A) compared with that of combination of pomalidomide, bortezomib and dexamethasone (Arm B) in participants with relapsed/refractory multiple myeloma (RRMM).
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.
- •Male or female, 18 years or older.
- •Have a confirmed diagnosis of multiple myeloma (MM) as defined by the International Myeloma Working Group (IMWG) criteria.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Have been previously treated with at least 1 prior line of MM therapy including a lenalidomide-containing regimen and must have documented disease progression during or after their most recent therapy. (Participants treated with lenalidomide ≥10 mg daily for at least 2 consecutive cycles are eligible).
- •Must have at least 1 aspect of measurable disease defined as one of the following;
- •Urine M-protein excretion greater than or equal to (≥)200 milligrams (mg) per 24-hour, or
- •Serum M-protein concentration ≥0.5 grams/deciliters (g/dL) (≥5.0 g/liter [L]), or
- •Serum free light chain (FLC) assay: involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum free light chain ratio (less than [<]0.26 or greater than [>]1.65) only if participant has no measurable urine or serum M spike.
- •Have undergone autologous stem cell transplant (ASCT) or are considered transplant ineligible. Participants with a history of ASCT are eligible for study participation provided the following eligibility criteria are met: a. ASCT was >100 days prior to the first dose of study medication. b. No active bacterial, viral, or fungal infection(s) present
- •All prior treatment-related toxicities (defined by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 5.0) must be less than or equal to (≤)Grade 1 at the time of enrolment, except for alopecia.
- •Adequate organ system functions as mentioned in the protocol.
- •Male and female participants agree to abide by protocol-defined contraceptive requirements.
排除标准
- •Active plasma cell leukemia, symptomatic amyloidosis or active polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, and skin changes (POEMS) syndrome at the time of screening.
- •Prior allogeneic SCT.
- •Systemic anti-myeloma therapy (including chemotherapy and systemic steroids) within 14 days or five half-lives (whichever is shorter) preceding the first dose of study drug; prior treatment with a monoclonal antibody drug within 30 days of receiving the first dose of study drugs.
- •Plasmapheresis within 7 days prior to the first dose of study drug.
- •Received prior treatment with or intolerant to pomalidomide.
- •Received prior Beta cell maturation antigen (BCMA) targeted therapy.
- •Intolerant to bortezomib or refractory to bortezomib (for example; participant experienced progressive disease during treatment, or within 60 days of completing treatment, with a bortezomib-containing regimen of 1.3 mg/meter square [m^2] twice weekly).
- •Evidence of cardiovascular risk including any of the following;
- •Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram abnormalities including second degree (Mobitz type II) or third degree atrioventricular (AV) block.
- •Recent history within (3 months of screening) of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting .
- •Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
- •Uncontrolled hypertension.
- •Any major surgery within the last 4 weeks.
- •Previous or concurrent invasive malignancy other than multiple myeloma, except:
- •The disease must be considered medically stable for at least 2 years; or
- •The participant must not be receiving active therapy, other than hormonal therapy for this disease.
- •Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to belantamab mafodotin or drugs chemically related to belantamab mafodotin, or any of the components of the study treatment.
- •Evidence of active mucosal or internal bleeding.
- •Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice.
- •Active infection requiring treatment.
- •Known or active human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C will be excluded unless the protocol-defined criteria are met.
- •Presence of active renal conditions (such as infection, severe renal impairment requiring dialysis or any other condition that could affect participant's safety).
- •Ongoing Grade 2 peripheral neuropathy with pain within 14 days prior to randomization or ≥Grade 3 peripheral neuropathy.
- •Active or history of venous and arterial thromboembolism within the past 3 months.
- •Contraindications to or unwilling to undergo protocol-required anti-thrombotic prophylaxis.
- •Current corneal disease except for mild punctate keratopathy.
- •Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including laboratory abnormalities) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures.
- •Pregnant or lactating female.
研究组 & 干预措施
Arm A: Belantamab mafodotin plus Pomalidomide and Dexamethasone
Experimental
干预措施: Belantamab mafodotin (Drug)
Arm A: Belantamab mafodotin plus Pomalidomide and Dexamethasone
Experimental
干预措施: Pomalidomide (Drug)
Arm B: Bortezomib plus Pomalidomide and Dexamethasone
Active Comparator
干预措施: Pomalidomide (Drug)
Arm A: Belantamab mafodotin plus Pomalidomide and Dexamethasone
Experimental
干预措施: Dexamethasone (Drug)
Arm B: Bortezomib plus Pomalidomide and Dexamethasone
Active Comparator
干预措施: Dexamethasone (Drug)
Arm B: Bortezomib plus Pomalidomide and Dexamethasone
Active Comparator
干预措施: Bortezomib (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Up to approximately 174 weeks
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 is defined as 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
- 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 approximately 473 weeks)
- Overall Response Rate (ORR)(Up to approximately 473 weeks)
- Complete Response Rate (CRR)(Up to approximately 473 weeks)
- Percentage of Participants With a Confirmed Very Good Partial Response (VGPR) or Better(Up to approximately 473 weeks)
- Time to Best Response (TTBR)(Up to approximately 473 weeks)
- Time to Response (TTR)(Up to approximately 473 weeks)
- Time to Progression (TTP)(Up to approximately 473 weeks)
- Progression-Free Survival 2 (PFS2)(Up to approximately 473 weeks)
- Number of Participants With Adverse Events (AEs)(Up to approximately 473 weeks)
- Number of Participants With Clinically Significant Changes in Hematology Parameters(Up to approximately 473 weeks)
- Number of Participants With Clinically Significant Changes in Clinical Chemistry Parameters(Up to approximately 473 weeks)
- Number of Participants With Abnormal Ocular Findings on Ophthalmic Examination(Up to approximately 473 weeks)
- Plasma Concentrations of Belantamab Mafodotin (ADC) at Indicated Time Points(Up to approximately 473 weeks)
- Plasma Concentrations of Monomethyl Auristatin-F With a Cysteine Linker (Cys-mcMMAF) at Indicated Time Points(Up to approximately 473 weeks)
- Area Under Plasma Concentration-time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration (C(Tlast)) [AUC (0-last)] for Pomalidomide(Up to approximately 473 weeks)
- Area Under Plasma Concentration-time Curve (AUC) From Time 0 to End of the Dosing Interval [AUC (0-tau)] for Pomalidomide(Up to approximately 473 weeks)
- Maximum Concentration (Cmax) for Pomalidomide(Up to approximately 473 weeks)
- Time of Cmax (Tmax) for Pomalidomide(Up to approximately 473 weeks)
- Trough Concentration Prior to the Next Dose for Each Cycle (Ctrough) for Pomalidomide(Up to approximately 473 weeks)
- Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast) for Pomalidomide(Up to approximately 473 weeks)
- Number of Participants With Positive Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin(Up to approximately 473 weeks)
- Titers of ADAs Against Belantamab Mafodotin(Up to approximately 473 weeks)
- Overall Survival (OS)(Up to approximately 473 weeks)
- Duration of Response (DoR)(Up to approximately 473 weeks)
- Minimal Residual Disease (MRD) Negativity Rate(Up to approximately 473 weeks)
- 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 approximately 473 weeks)
- Change From Baseline in Quality of Life Questionnaire 20-item Multiple Myeloma Module (QLQMY20)(Up to approximately 473 weeks)
- Change From Baseline in HRQoL as Measured by EORTC IL52(Up to approximately 473 weeks)
研究者
研究点 (123)
Loading locations...
相似试验
终止
1 期
Sub-study of Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Dostarlimab (GSK4057190) in Participants With RRMMRelapsed/Refractory Multiple MyelomaNCT06655818GlaxoSmithKline4
终止
1 期
Platform Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With aOX40 (GSK3174998) in Participants With RRMMRelapsed/Refractory Multiple MyelomaNCT06160609GlaxoSmithKline9
已完成
2 期
Japanese Phase 2 Study to Evaluate the Efficacy and Safety of Pomalidomide in Subjects With Relapsed and Refractory Multiple MyelomaMultiple MyelomaNCT02011113Celgene Corporation36
进行中（未招募）
2 期
Study to Investigate Alternative Dosing Regimens of Belantamab Mafodotin in Participants With Relapsed or Refractory Multiple MyelomaMultiple MyelomaNCT05064358GlaxoSmithKline177
进行中（未招募）
1 期
Blmf, Lenalidomide and Dexamethasone in Transplant-ineligible Patients With Newly Diagnosed Multiple MyelomaMultiple MyelomaNCT04808037Hellenic Society of Hematology66
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 yearDREAMM-8 Trial: Belantamab Mafodotin Plus Pomalidomide and Dexamethasone Significantly Improves PFS in Multiple Myeloma- The DREAMM-8 trial evaluated belantamab mafodotin, pomalidomide, and dexamethasone (BPd) versus pomalidomide, bortezomib, and dexamethasone (PVd) in relapsed/refractory multiple myeloma patients.
- BPd demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to PVd (HR, 0.52; 95% CI, 0.37-0.73; P < .001).
- The overall response rate was higher in the BPd arm (77%) compared to the PVd arm (72%), with deeper responses observed, including higher rates of complete response or better (40% vs 16%).
- BPd showed a higher rate of complete response or better plus minimal residual disease negativity (24%) compared to PVd (5%), indicating a more effective disease control.last yearAdvancements in Oncology: CAR-T Therapy for Myeloma, Cologuard Plus Approval, and NSCLC Treatment• HBI0101, a novel BCMA-directed CAR T-cell therapy, shows high efficacy and manageable safety in relapsed/refractory multiple myeloma patients, offering a promising treatment option.
• Cologuard Plus receives FDA approval as a noninvasive stool DNA test for colorectal cancer screening in adults 45 and older, demonstrating improved detection rates.
• Neoadjuvant nivolumab plus chemotherapy, followed by adjuvant nivolumab, gains FDA approval for operable stage IIA to IIIB non-small cell lung cancer, significantly improving event-free survival.
• Belantamab mafodotin-blmf combined with pomalidomide and dexamethasone shows meaningful improvements in relapsed/refractory multiple myeloma compared to bortezomib-based regimens.last year
7 articles
1 / 2