A Phase I/II, Open-label, Dose Escalation and Expansion Study to Evaluate Safety, Tolerability, and Clinical Activity of the Antibody-Drug Conjugate GSK2857916 Administered in Combination With Lenalidomide Plus Dexamethasone (Arm A), or Bortezomib Plus Dexamethasone (Arm B) in Participants With Relapsed / Refractory Multiple Myeloma - DREAMM-6
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 153
- 试验地点
- 1
- 主要终点
- Change From Baseline in Urine Specific Gravity
研究概览
简要总结
This study will evaluate the safety and tolerability profile of belantamab mafodotin when administered in combination with approved regimens of either Lenalidomide Plus Dexamethasone [Len/Dex (Treatment A)] or Bortezomib Plus Dexamethasone [Bor/Dex (Treatment B)] in participants with RRMM, i.e., those who have relapsed or who are refractory to at least 1 line of approved therapy.
Participants receiving treatment A, may continue combination treatment until the occurrence of progressive disease (PD), intolerable adverse events (AEs ), consent withdrawal, death or end of study. The participants receiving treatment B, may continue combination treatment for a total of up to 8 cycles. After 8 cycles of combination therapy, the participants will continue treatment with belantamab mafodotin, as a monotherapy until the occurrence of PD, intolerable AEs, consent withdrawal, death or end of study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This is an open-label study; therefore, no blinding of treatment identity will be done for both treatments.
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 (at the time consent is obtained).
- •Have confirmed diagnosis of Multiple Myeloma (MM) as defined by the IMWG.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 for Arm A and 0 to 2 for Arm B.
- •Have undergone stem cell transplant (SCT), or are considered transplant ineligible.
- •Have been previously treated with at least 1 prior line of MM therapy, and must have documented disease progression during or after their most recent therapy.
- •Must have at least ONE aspect of measurable disease, defined as one the following: Urine M-protein excretion >=200 milligram (mg)/24 hours, or; Serum M-protein concentration >=0.5 gram (g)/deciliter (dL) (>=5.0 g/Liter), or; Serum free light chain (FLC) assay: involved FLC level >=10 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: Autologous SCT was >100 days prior to study enrollment; No active bacterial, viral, or fungal infection(s) present; Participant meets the remainder of the eligibility criteria.
- •All prior treatment-related toxicities (defined by National Cancer Institute Common Toxicity Criteria for Adverse Events [NCI-CTCAE], Version 4.03, 2010) must be Grade <= 1 at the time of enrollment, except for alopecia. Participants with Grade 2 neuropathy can be enrolled into Len/Dex treatment arm, but not into Bor/Dex treatment arm.
- •Adequate organ system functions as defined by the laboratory assessments.
- •The contraceptions used by female participants be consistent with local regulations, regarding methods of contraception for those participating in clinical studies. 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 child bearing 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 4 months after the last dose of belantamab mafodotin and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. 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.
- •WOCBP Participants Assigned to Arm A:
- •Due to lenalidomide being a thalidomide analogue with risk for embryo-fetal 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 lenalidomide, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of lenalidomide treatment. Thereafter, WOCBP participants must use a contraceptive method that is highly effective (with a failure rate of <1% per year) for a further 3 months, and agree not to donate eggs (ova, oocytes) for the purpose of reproduction during this period: Two negative pregnancy tests must be obtained prior to initiating lenalidomide therapy. The first test should be performed within 10-14 days and the second test within 24 hours prior to prescribing lenalidomide therapy.
- •WOCBP Participants Assigned to Arm B
- •WOCBP assigned to Arm B must have a negative highly sensitive serum pregnancy test within 72 hours of dosing on C1D1 and agree to use effective contraception during the study and for 4 months after the last dose of belantamab mafodotin or 7 months from the last dose of bortezomib, whichever is longer.
- •Male participants using contraception 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:
- •Arm A: from the time of first dose of study until 6 months after the last dose of belantamab mafodotin 4 weeks after the last dose of lenalidomide, whichever is longer, to allow for clearance of any altered sperm.
- •Arm B: from the time of first dose of study until 6 months after the last dose of belantamab mafodotin or 4 months from the last dose of bortezomib (whichever is the longer) to allow for clearance of any altered sperm.
- •Male participants must agree to refrain from donating sperm and 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.
- •Agree to use a male condom even if they have undergone a successful vasectomy and female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year when having sexual intercourse. Male participants should also use a condom with pregnant females. If the female partner of the male participant is pregnant at the time of enrollment, or becomes pregnant during the trial, the male participant must agree to remain abstinent (if it is consistent with their preferred and usual lifestyle) or use a male condom.
排除标准
- •Systemic anti-myeloma therapy (including systemic steroids) 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 longer) 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 allogenic stem cell transplant. Note: Participants who have undergone syngeneic transplant will be allowed only if they have no history and no currently active, graft versus host disease (GvHD).
- •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, provided they fulfill 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 to the study procedures.
- •Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, or otherwise stable chronic liver disease per investigator's assessment).
- •Participants with invasive 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. Note: 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 ECG abnormalities including 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 3 months of Screening; Class III or IV heart failure as defined by the New York Heart Association functional classification system; Uncontrolled hypertension.
- •Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, or any of the components of the study treatment.
- •Pregnant or lactating female.
- •Active infection requiring 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).
- •Current corneal disease except for mild punctuate keratopathy.
- •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.
- •Current corneal disease except for mild punctute keratopathy.
- •Participants Assigned to Treatment A (belantamab mafodotin plus Len/Dex): Participants unable to tolerate antithrombotic prophylaxis must be excluded; Discontinuation of prior treatment with lenalidomide due to intolerable AEs.
- •Participants Assigned to Treatment B (belantamab mafodotin plus Bor/Dex): Unacceptable AEs from previous bortezomib treatment; Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain from previous bortezomib treatment; Intolerance or contraindications to anti-viral prophylaxis.
研究组 & 干预措施
Arm A: Belantamab mafodotin+lenalidomide +dexamethasone
Participants will receive SINGLE full dose of belantamab mafodotin as 2.5 mg/kg and 1.9 mg/kg on Day 1 of every 28-day cycle as a 30-60 min infusion.
SPLIT: belantamab mafodotin will be administered in two equal divided doses, 2.5 mg/kg SPLIT dose of a 1.25 mg/kg dose on Day 1 and a 1.25 mg/kg dose on Day 8 of each 28-day cycle.
STRETCH: belantamab mafodotin will be administered as 1.9 mg/kg dose on Day 1 of every alternate 28-day cycles (C1, C3, C5, C7 and so on.) Participants will also receive Lenalidomide 25 mg or 10 mg orally daily, on Days 1-21 of each 28 day cycle with Dexamethasone, 40 mg weekly per oral (PO)/intravenously (IV) on Days 1,8,15, & 22 of each cycle.
干预措施: Belantamab mafodotin (Drug)
Arm A: Belantamab mafodotin+lenalidomide +dexamethasone
Participants will receive SINGLE full dose of belantamab mafodotin as 2.5 mg/kg and 1.9 mg/kg on Day 1 of every 28-day cycle as a 30-60 min infusion.
SPLIT: belantamab mafodotin will be administered in two equal divided doses, 2.5 mg/kg SPLIT dose of a 1.25 mg/kg dose on Day 1 and a 1.25 mg/kg dose on Day 8 of each 28-day cycle.
STRETCH: belantamab mafodotin will be administered as 1.9 mg/kg dose on Day 1 of every alternate 28-day cycles (C1, C3, C5, C7 and so on.) Participants will also receive Lenalidomide 25 mg or 10 mg orally daily, on Days 1-21 of each 28 day cycle with Dexamethasone, 40 mg weekly per oral (PO)/intravenously (IV) on Days 1,8,15, & 22 of each cycle.
干预措施: Lenalidomide (Drug)
Arm A: Belantamab mafodotin+lenalidomide +dexamethasone
Participants will receive SINGLE full dose of belantamab mafodotin as 2.5 mg/kg and 1.9 mg/kg on Day 1 of every 28-day cycle as a 30-60 min infusion.
SPLIT: belantamab mafodotin will be administered in two equal divided doses, 2.5 mg/kg SPLIT dose of a 1.25 mg/kg dose on Day 1 and a 1.25 mg/kg dose on Day 8 of each 28-day cycle.
STRETCH: belantamab mafodotin will be administered as 1.9 mg/kg dose on Day 1 of every alternate 28-day cycles (C1, C3, C5, C7 and so on.) Participants will also receive Lenalidomide 25 mg or 10 mg orally daily, on Days 1-21 of each 28 day cycle with Dexamethasone, 40 mg weekly per oral (PO)/intravenously (IV) on Days 1,8,15, & 22 of each cycle.
干预措施: Dexamethasone (Drug)
Arm B: Belantamab mafodotin+bortezomib+dexamethasone
Participants will receive SINGLE full dose of belantamab mafodotin as 3.4 mg/kg; 2.5 mg/kg; 1.9 mg/kg on Day 1 of each 21-day cycle. SPLIT: belantamab mafodotin will be administered in two equal divided doses: 3.4 mg/kg SPLIT as 1.7 mg/kg dose on Day 1 & 1.7 mg/kg dose on Day 8; 2.5 mg/kg SPLIT dosing as 1.25 mg/kg dose on Day 1 & 1.25 mg/kg dose on Day 8 of each 21-day cycle. STRETCH: belantamab mafodotin will be administered as single dose of 2.5 mg/kg on Day 1 of every alternate 21-day cycles (C1,C3,C5,C7 & so on), 1.9 mg/kg administered on Day 1 of every alternate 21-day cycles (C1,C3,C5,C7 and so on). Step Down(S/D) STRETCH=belantamab mafodotin 2.5 mg/kg dose will be administered on Day 1 C1 followed by 1.9 mg/kg starting dose on Day1 of alternate 21-day cycles C3 onwards (C3,C5,C7, & so on). Bortezomib will be administered at 1.3 mg/m^2 SC/IV on Days 1,4,8, & 11 of every 21-day cycle. Dex will be administered at 20 mg PO or IV on Days 1,2,4,5,8,9,11, & 12 of every 21-day cycle.
干预措施: Belantamab mafodotin (Drug)
Arm B: Belantamab mafodotin+bortezomib+dexamethasone
Participants will receive SINGLE full dose of belantamab mafodotin as 3.4 mg/kg; 2.5 mg/kg; 1.9 mg/kg on Day 1 of each 21-day cycle. SPLIT: belantamab mafodotin will be administered in two equal divided doses: 3.4 mg/kg SPLIT as 1.7 mg/kg dose on Day 1 & 1.7 mg/kg dose on Day 8; 2.5 mg/kg SPLIT dosing as 1.25 mg/kg dose on Day 1 & 1.25 mg/kg dose on Day 8 of each 21-day cycle. STRETCH: belantamab mafodotin will be administered as single dose of 2.5 mg/kg on Day 1 of every alternate 21-day cycles (C1,C3,C5,C7 & so on), 1.9 mg/kg administered on Day 1 of every alternate 21-day cycles (C1,C3,C5,C7 and so on). Step Down(S/D) STRETCH=belantamab mafodotin 2.5 mg/kg dose will be administered on Day 1 C1 followed by 1.9 mg/kg starting dose on Day1 of alternate 21-day cycles C3 onwards (C3,C5,C7, & so on). Bortezomib will be administered at 1.3 mg/m^2 SC/IV on Days 1,4,8, & 11 of every 21-day cycle. Dex will be administered at 20 mg PO or IV on Days 1,2,4,5,8,9,11, & 12 of every 21-day cycle.
干预措施: Dexamethasone (Drug)
Arm B: Belantamab mafodotin+bortezomib+dexamethasone
Participants will receive SINGLE full dose of belantamab mafodotin as 3.4 mg/kg; 2.5 mg/kg; 1.9 mg/kg on Day 1 of each 21-day cycle. SPLIT: belantamab mafodotin will be administered in two equal divided doses: 3.4 mg/kg SPLIT as 1.7 mg/kg dose on Day 1 & 1.7 mg/kg dose on Day 8; 2.5 mg/kg SPLIT dosing as 1.25 mg/kg dose on Day 1 & 1.25 mg/kg dose on Day 8 of each 21-day cycle. STRETCH: belantamab mafodotin will be administered as single dose of 2.5 mg/kg on Day 1 of every alternate 21-day cycles (C1,C3,C5,C7 & so on), 1.9 mg/kg administered on Day 1 of every alternate 21-day cycles (C1,C3,C5,C7 and so on). Step Down(S/D) STRETCH=belantamab mafodotin 2.5 mg/kg dose will be administered on Day 1 C1 followed by 1.9 mg/kg starting dose on Day1 of alternate 21-day cycles C3 onwards (C3,C5,C7, & so on). Bortezomib will be administered at 1.3 mg/m^2 SC/IV on Days 1,4,8, & 11 of every 21-day cycle. Dex will be administered at 20 mg PO or IV on Days 1,2,4,5,8,9,11, & 12 of every 21-day cycle.
干预措施: Bortezomib (Drug)
结局指标
主要结局
Change From Baseline in Urine Specific Gravity
时间窗: Baseline (Day 1) and up to approximately 4.5 years
Urine samples were collected to analyze urine specific gravity using dipstick method. Baseline (Day 1) was defined as latest pre-dose assessment with a non-missing value, including unscheduled visits.
Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
时间窗: Baseline (Day 1) and up to approximately 4.5 years
Blood pressures (DBP and SBP) were measured after resting for at least 5 minutes in a supine or semi-recumbent position. Baseline (Day 1) was defined as latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Change From Baseline in Vital Signs : Pulse Rate
时间窗: Baseline (Day 1) and up to approximately 4.5 years
Pulse rate was measured after resting for at least 5 minutes in a supine or semi-recumbent position. Baseline (Day 1) was defined as latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Number of Participants With Dose Limiting Toxicities (DLTs), Treatment A
时间窗: Up to 28 days
DLT is an adverse event (AE) that is considered by the investigator to be clinically relevant and attributed to the study therapy during the 28 day DLT period and meets at least one of the DLT criteria: Grade 3 or greater febrile neutropenia lasting \>48 hours (h) despite adequate treatment; Grade 4 thrombocytopenia \<25,000/mm\^3 accompanied by significant bleeding; any Grade 3 or greater non-hematologic laboratory value (if laboratory abnormality persist \>48 h despite supportive treatment or abnormality leading to hospitalisation); non-hematologic toxicity which does not resolve with appropriate supportive treatment within 48 h, Grade 4 corneal adverse events; and other organ specific toxicities (liver toxicity that causes discontinuation of treatment).
Number of Participants With Worst-Case Amount of Increase From Baseline Value in Corrected QT Interval Using Fredericia's Formula (QTcF)
时间窗: Up to approximately 4.5 years
12-lead electrocardiogram (ECGs) were obtained using an automated ECG machine that automatically calculated the QTcF intervals. QTc values are categorized into the clinical concern ranges which are specific to changes in QTc: 31-60 milliseconds (msec), and \>60 msec, and \>530msec. An increase is defined relative to Baseline. Baseline (Day 1) was defined as latest pre-dose assessment with non-missing value, including unscheduled visits. Data of number of participants with worst-case increase post baseline is presented.
Number of Participants With Worst-case Grade Change From Baseline in Hematology Parameters
时间窗: Baseline (Day 1) and up to approximately 4.5 years
Blood samples were collected for analysis of following hematology parameters: Hemoglobin (hemoglobin increased and anemia), Lymphocytes (lymphocyte count increased and lymphocyte count decreased), Neutrophils, Platelets and Leukocytes (leukocytosis and white blood cells decreased). The laboratory parameters were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03. Grade (G) 1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Baseline (Day 1) was defined as latest pre-dose assessment with non-missing value, including unscheduled visits. Any worst-case post baseline increases in grade along with any increase to a maximum G3 and a maximum G4 are presented.
Change From Baseline in Urine Potential of Hydrogen (pH)
时间窗: Baseline (Day 1) and up to approximately 4.5 years
Urine samples were collected to analyze urine pH levels. Baseline (Day 1) was defined as latest pre-dose assessment with non-missing value, including unscheduled visits.
Overall Response Rate (ORR) as Defined by the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma (MM)
时间窗: Up to approximately 4.5 years
ORR was defined as the percentage of participants with a confirmed partial response (PR) or better (i.e., PR, very good partial response \[VGPR\], complete response \[CR\] and stringent complete response \[sCR\]), according to the International Myeloma Working Group (IMWG) Response Criteria. CR: negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasmacytomas in the bone marrow; sCR: stringent complete response, CR as above plus normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR: serum and urine M-component detectable by immunofixation but not on electrophoresis OR \>= 90% reduction in serum M-component plus urine M-component \<100 mg/24 h; PR: \>=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or to \<200 mg/24 h. Confidence intervals were based on the exact method.
Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters
时间窗: Baseline (Day 1) and up to approximately 4.5 years
Blood samples were collected for analysis of following clinical chemistry parameters: Direct Bilirubin (DB), Calcium, Chloride, Carbon Dioxide (CO2), lactate dehydrogenase (LDH) and Protein. The summaries of worst-case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE version 4.03. The number of participants with decreases to low from baseline, changes to normal or no changes from baseline, and increases to high values from baseline have been presented. Baseline (Day 1) was defined as latest pre-dose assessment with non-missing value, including unscheduled visits.
Number of Participants With DLTs, Treatment B
时间窗: Up to 21 days
DLT is an adverse event (AE) that is considered by the investigator to be clinically relevant and attributed to the study therapy during the 21 day DLT period and meets at least one of the DLT criteria: Grade 3 or greater febrile neutropenia lasting \>48 hours (h) despite adequate treatment; Grade 4 thrombocytopenia \<25,000/mm\^3 accompanied by significant bleeding; any Grade 3 or greater non-hematologic laboratory value (if laboratory abnormality persist \>48 h despite supportive treatment or abnormality leading to hospitalisation); non-hematologic toxicity which does not resolve with appropriate supportive treatment within 48 h, Grade 4 corneal adverse events; and other organ specific toxicities (liver toxicity that causes discontinuation of treatment).
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to approximately 4.5 years
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent disability/incapacity or Is a congenital anomaly/birth defect, Other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function. SAEs are subset of AEs. A summary of number of participants with any AEs and SAEs are presented. AEs were coded using the Medical Dictionary for Regulatory Affairs (MedDRA dictionary).
Number of Participants With Worst-case Change Post-baseline in Hematology Parameters
时间窗: Baseline (Day 1) and up to approximately 4.5 years
Blood samples were collected for the analysis of following hematology parameters: basophils, eosinophils, hematocrit, mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), monocytes, erythrocytes and reticulocyte. The summaries of worst-case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE version 4.03. The number of participants with decreases to low from baseline, changes to normal or no changes from baseline, and increases to high values from baseline have been presented. Baseline (Day 1) was defined as latest pre-dose assessment with non-missing value, including unscheduled visits.
Number of Participants With Worst-case Grade Change From Baseline in Clinical Chemistry Parameters
时间窗: Baseline (Day 1) and up to approximately 4.5 years
Blood samples were collected for analysis of following clinical chemistry parameters: Hyperglycemia, Hypoglycemia, Albumin, Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase, (AST), Bilirubin, Creatine Kinase (CK), Creatinine, Gamma Glutamyl Transferase (GGT), Hyperkalemia, Hypokalemia, Hypermagnesemia, Hypomagnesemia, Phosphate, Hypernatremia, Hyponatremia, Urate, Hypercalcemia and Hypocalcemia. Laboratory parameters were graded according to CTCAE v4.03. Grade (G) 1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Baseline (Day 1) was defined as latest pre-dose assessment with non-missing value, including unscheduled visits. Any worst-case post baseline increases in grade along with any increase to a maximum G3 and a maximum G4 are presented.
Number of Participants With Worst-case Change Post Baseline Urinalysis Results: Occult Blood and Protein
时间窗: Baseline (Day 1) and up to approximately 4.5 years
Urine samples were collected to analyze presence of occult blood and protein in urine by dipstick method. Data for worst-case post baseline urinalysis results is presented. Result for urinalysis parameters were recorded as no change/decreased and increase to trace, 1+, 2+, 3+, \>3+ indicating proportional concentrations in the urine sample. Baseline (Day 1) was defined as latest pre-dose assessment with non-missing value, including unscheduled visits.
Change From Baseline in Vital Signs : Temperature
时间窗: Baseline (Day 1) and up to approximately 4.5 years
Temperature was measured after resting for at least 5 minutes in a supine or semi-recumbent position. Baseline (Day 1) was defined as latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated as post-dose visit value minus Baseline value.
次要结局
- Maximum Observed Concentration (Cmax) for Belantamab Mafodotin Antibody-drug Conjugate (ADC), Treatment A(Pre-Dose, 0, 2 and 24 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 8)
- Time to Reach Maximum Observed Concentration (Tmax) for Belantamab Mafodotin ADC, Treatment A(Pre-Dose, 0, 2 and 24 Hours Post-Dose on Cycle 1 Day 1 and Cycle 1 Day 8)
- Tlast for Belantamab Mafodotin (Total Antibody), Treatment A(Pre-Dose, 0, 2 and 24 Hours Post-Dose on Cycle 1 Day 1 and Cycle 1 Day 4; Cycle 1 Day 8; Cycle 1 Day 11; Cycle 1 Day 15-21; Cycle 1 Day 29; pre-dose Cycle 2 Day 28; pre-dose Cycle 3 Day 8)
- Cmax for Belantamab Mafodotin (Total Antibody) Treatment B(Pre-Dose, 0, 2 and 24 Hours Post-Dose on Cycle 1 Day 1 and Cycle 1 Day 8)
- C-EOI for Belantamab Mafodotin (Total Antibody), Treatment B(Pre-Dose, Post-Dose 0, 2 and 24 Hour on Cycle 1 Day 1 and Cycle 1 Day 8; Pre-Dose and Post-Dose on Week 4 Day 1, Week 7 Day 1, Week 7 Day 8, Week 7 Day 11, Week 10 Day 1, Week 13 Day 1, Week 13 Day 8)
- Cmax for Belantamab Mafodotin Cysteine Maleimidocaproyl Monomethyl Auristatin F (Cys-mcMMAF), Treatment A(Pre-Dose, 0, 2 and 24 Hours Post-Dose on Cycle 1 Day 1 and Cycle 1 Day 8)
- AUC (0-336h) for Belantamab Mafodotin (Cys-mcMMAF), Treatment A(Pre-dose, 0, 2, and 24 Hours Post Dose on Cycle 1 Day 1; Cycle 1 Day 4; Cycle 1 Day 8; Cycle 1 Day 11; Cycle 1 Day 14)
- AUC (0-672h) for Belantamab Mafodotin ADC, Treatment A(Pre-Dose, 0, 2 and 24 Hours Post-Dose on Cycle 1 Day 1; Cycle 1 Day 4; Cycle 1 Day 8; Cycle 1 Day 11; Cycle 1 Day 15-21; Cycle 1 Day 28)
- Trough Concentration Prior to the Next Dose for Each Cycle (Ctrough) for Belantamab Mafodotin ADC, Treatment A(Cycle 1: Pre-Dose, 0, 2 and 24 Hours Post-Dose on Days 1 and 8; Weeks 5, 9, and 13: Pre-Dose and Post-Dose on Days 1 and 8)
- Observed Plasma Concentration at the End of Infusion (C-EOI) for Belantamab Mafodotin ADC, Treatment A(Cycle 1: Pre-Dose, 0, 2 and 24 Hours Post-Dose on Days 1 and Day 8; Weeks 5, 9, and 13: Pre-Dose and Post-Dose on Days 1 and 8)
- Time of Last Observed Quantifiable Concentration (Tlast) for Belantamab Mafodotin ADC, Treatment A(Pre-Dose, 0, 2 and 24 Hours Post-Dose on Cycle 1 Day 1 and Cycle 1 Day 4; Cycle 1 Day 8; Cycle 1 Day 11; Cycle 1 Day 15-21; Cycle 1 Day 29; pre-dose Cycle 2 Day 28)
- Cmax for Belantamab Mafodotin ADC, Treatment B(Pre-Dose, 0, 2 and 24 Hours Post-Dose on Cycle 1 Day 1 and Cycle 1 Day 8)
- AUC (0-504h) for Belantamab Mafodotin ADC, Treatment B(Pre-Dose, 0, 2 and 24 Hours Post Dose on Cycle 1 Day 1; Cycle 1 Day 4; Cycle 1 Day 8; Cycle 1 Day 11; Cycle 1 Day 21)
- AUC (0-1008h) for Belantamab Mafodotin ADC, Treatment B(Pre-Dose, 0, 2 and 24 Hours Post Dose on Cycle 1 Day 1; Cycle 1 Day 4; Cycle 1 Day 11; Cycle 1 Day 22; Pre-Dose and Post-Dose on Week 5 Day 7)
- AUC (0-504h) for Belantamab Mafodotin (Total Antibody), Treatment B(Pre-Dose, 0, 2 and 24 Hours Post Dose on Cycle 1 Day 1; Cycle 1 Day 4; Cycle 1 Day 8; Cycle 1 Day 11; Cycle 1 Day 21)
- AUC(0-168h) for Belantamab Mafodotin (Cys-mcMMAF), Treatment B(Pre-dose, 0, 2, and 24 Hours Post Dose on Cycle 1 Day 1, Cycle 1 Day 4; and Cycle 1 Day 7)
- AUC (0-4h) for Lenalidomide (10 mg), Treatment A(Pre-Dose, 0.5, 1, 2 and 4 hours on Cycle 1 Day 1 post lenalidomide dose)
- Tlast for Lenalidomide (10 mg), Treatment A(Pre-Dose, Post dose on Cycle 1 Day 1)
- AUC (0-t) for Bortezomib, Treatment B(Pre-dose, 5 minute, 0.25, 0.5, 1, 2, 4, 6, 10, 24, 48 and 72 hour post bortezomib dose)
- Area Under the Concentration Time Curve (AUC) From Time 0 to 504 Hours (0-504h) for Belantamab Mafodotin ADC, Treatment A(Pre-Dose, 0, 2 and 24 Hours Post-Dose on Cycle 1 Day 1; Cycle 1 Day 4; Cycle 1 Day 8; Cycle 1 Day 11; Cycle 1 Day 15-21)
- AUC (0-1008h) for Belantamab Mafodotin (Total Antibody), Treatment A(Pre-Dose, 0, 2 and 24 Hours Post-Dose on Cycle 1 Day 1; Cycle 1 Day 4; Cycle 1 Day 8; Cycle 1 Day 29; Pre-Dose and Post-Dose on Week 5 Day 7)
- AUC (0-1008h) for Belantamab Mafodotin (Total Antibody), Treatment B(Pre-Dose, 0, 2 and 24 Hours Post Dose on Cycle 1 Day 1; Cycle 1 Day 4; Cycle 1 Day 11; Cycle 1 Day 22; Pre-Dose and Post-Dose on Week 5 Day 7)
- AUC(0-24h) for Lenalidomide (25 mg), Treatment A(Pre-Dose, 0.5, 1, 2, 4 and 24 hours on Cycle 1 Day 1 post lenalidomide dose)
- Tmax for Lenalidomide (25 mg), Treatment A(Pre-Dose, 0.5, 1, 2, 4 and 24 hours on Cycle 1 Day 1 post lenalidomide dose)
- Tlast for Lenalidomide (25 mg), Treatment A(Pre-Dose, Post dose on Cycle 1 Day 1)
- Tlast for Bortezomib, Treatment B(Pre-Dose, Post dose on Cycle 1 Day 3)
- Tmax for Belantamab Mafodotin ADC, Treatment B(Pre-Dose, 0, 2 and 24 Hours Post-Dose on Cycle 1 Day 1 and Cycle 1 Day 8)
- Tlast for Belantamab Mafodotin ADC, Treatment B(Pre-Dose Cycle 1 Day 1 to pre-dose Cycle 5 Day 1)
- Ctrough for Belantamab Mafodotin ADC, Treatment B(Pre-Dose, Post-Dose 0, 2 and 24 Hour on Cycle 1 Day 1 and Cycle 1 Day 8; Pre-Dose and Post-Dose on Week 4 Day 1, Week 7 Day 1, Week 10 Day 1, Week 13 Day 1, Week 13 Day 8)
- C-EOI for Belantamab Mafodotin ADC, Treatment B(Pre-Dose, Post-Dose 0, 2 and 24 Hour on Cycle 1 Day 1 and Cycle 1 Day 8; Pre-Dose and Post-Dose on Week 4 Day 1, Week 7 Day 1, Week 7 Day 8, Week 7 Day 11, Week 10 Day 1, Week 10 Day 8, Week 13 Day 1, Week 13 Day 8)
- AUC (0-672h) for Belantamab Mafodotin (Total Antibody), Treatment A(Pre-Dose, 0, 2 and 24 Hours Post-Dose on Cycle 1 Day 1; Cycle 1 Day 4; Cycle 1 Day 8; Cycle 1 Day 11; Cycle 1 Day 15-21; Cycle 1 Day 28)
- AUC (0-168h) for Belantamab Mafodotin (Cys-mcMMAF), Treatment A(Pre-dose, 0, 2, and 24 Hours Post Dose on Cycle 1 Day 1, and Cycle 1 Day 8)
- Tlast for Belantamab Mafodotin (Cys-mcMMAF), Treatment A(Pre-Dose Cycle 1 Day 1 to pre-dose Cycle 1 Day 15)
- AUC(0-24h) for Lenalidomide (10 mg), Treatment A(Pre-Dose, 0.5, 1, 2, 4 and 24 hours on Cycle 1 Day 1 post lenalidomide dose)
- AUC (0-72h) for Bortezomib, Treatment B(Pre-dose, 5 minute, 0.25, 0.5, 1, 2, 4, 6, 10, 24, 48 and 72 hour post bortezomib dose)
- Tmax for Bortezomib, Treatment B(Pre-dose, 5 minute, 0.25, 0.5, 1, 2, 4, 6, 10, 24, 48 and 72 hour post bortezomib dose)
- Cmax for Belantamab Mafodotin (Cys-mcMMAF) Treatment B(Pre-Dose, 0, 2 and 24 Hours Post-Dose on Cycle 1 Day 1 and Cycle 1 Day 8)
- Cmax for Belantamab Mafodotin (Total Antibody), Treatment A(Pre-Dose, 0, 2 and 24 Hours Post-Dose on Cycle 1 Day 1 and Cycle 1 Day 8)
- AUC (0-504h) for Belantamab Mafodotin (Total Antibody), Treatment A(Pre-Dose, 0, 2 and 24 Hours Post-Dose on Cycle 1 Day 1; Cycle 1 Day 4; Cycle 1 Day 8; Cycle 1 Day 11; Cycle 1 Day 15-21)
- AUC(0-1344h) for Belantamab Mafodotin (Total Antibody), Treatment A(Pre-Dose, 0, 2 and 24 Hours Post-Dose on Cycle 1 Day 1; Cycle 1 Day 4; Cycle 1 Day 8; Cycle 1 Day 29; Pre-Dose and Post-Dose on Week 7 Day 7)
- Tmax for Belantamab Mafodotin (Total Antibody), Treatment A(Pre-Dose, 0, 2 and 24 Hours Post-Dose on Cycle 1 Day 1 and Cycle 1 Day 8)
- Ctrough for Belantamab Mafodotin (Total Antibody), Treatment A(Pre-Dose, Post-Dose 0, 2 and 24 Hour on Cycle 1 Day 1 and Cycle 1 Day 8; Pre-Dose and Post-Dose on Week 5 Day 1, Week 5 Day 8, Week 9 Day 1, Week 9 Day 8, Week 13 Day 1, Week 13 Day 8)
- C-EOI for Belantamab Mafodotin (Total Antibody), Treatment A(Pre-Dose, Post-Dose 0, 2 and 24 Hour on Cycle 1 Day 1 and Cycle 1 Day 8; Pre-Dose and Post-Dose on Week 5 Day 1, Week 5 Day 8, Week 9 Day 1, Week 9 Day 8, Week 13 Day 1, Week 13 Day 8)
- Tmax for Belantamab Mafodotin (Total Antibody), Treatment B(Pre-Dose, 0, 2 and 24 Hours Post-Dose on Cycle 1 Day 1 and Cycle 1 Day 8)
- Tlast for Belantamab Mafodotin (Total Antibody), Treatment B(Pre-Dose Cycle 1 Day 1 to pre-dose Cycle 9 Day 1)
- Ctrough for Belantamab Mafodotin (Total Antibody), Treatment B(Pre-Dose, Post-Dose 0, 2 and 24 Hour on Cycle 1 Day 1 and Cycle 1 Day 8; Pre-Dose and Post-Dose on Week 4 Day 1, Week 7 Day 1, Week 7 Day 8, Week 10 Day 1, Week 13 Day 1, Week 13 Day 8)
- Tmax for Belantamab Mafodotin (Cys-mcMMAF), Treatment A(Pre-Dose, 0, 2 and 24 Hours Post-Dose on Cycle 1 Day 1 and Cycle 1 Day 8)
- C-EOI for Belantamab Mafodotin (Cys-mcMMAF), Treatment A(Pre-Dose, Post-Dose 0, 2 and 24 Hour on Cycle 1 Day 1 and Cycle 1 Day 8; Pre-Dose and Post-Dose on Week 5 Day 1, Week 7 Day 8, Week 9 Day 1, Week 9 Day 8, Week 13 Day 1, Week 13 Day 8)
- Tmax for Belantamab Mafodotin (Cys-mcMMAF), Treatment B(Pre-Dose, 0, 2 and 24 Hours Post-Dose on Cycle 1 Day 1 and Cycle 1 Day 8)
- AUC (0-4h) for Lenalidomide (25 mg), Treatment A(Pre-Dose, 0.5, 1, 2 and 4 hours on Cycle 1 Day 1 post lenalidomide dose)
- Tmax for Lenalidomide (10 mg), Treatment A(Pre-Dose, 0.5, 1, 2, 4 and 24 hours on Cycle 1 Day 1 post lenalidomide dose)
- Cmax for Bortezomib, Treatment B(Pre-Dose, 0.5, 1, 2, 4 and 24 Hours Post-Dose on Cycle 1 Day 1)
- Tlast for Belantamab Mafodotin (Cys-mcMMAF), Treatment B(Pre-Dose Cycle 1 Day 1 to pre-dose Cycle 2 Day 1)
- C-EOI for Belantamab Mafodotin (Cys-mcMMAF), Treatment B(Pre-Dose, Post-Dose 0, 2 and 24 Hour on Cycle 1 Day 1 and Cycle 1 Day 8; Pre-Dose and Post-Dose on Week 4 Day 1, Week 7 Day 1, Week 7 Day 8, Week 7 Day 11, Week 10 Day 1, Week 10 Day 8, Week 13 Day 1, Week 13 Day 8)
- Cmax for Lenalidomide (25 mg), Treatment A(Pre-Dose, 0.5, 1, 2, 4 and 24 hours on Cycle 1 Day 1 post lenalidomide dose)
- Cmax for Lenalidomide (10 mg), Treatment A(Pre-Dose, 0.5, 1, 2, 4 and 24 hours on Cycle 1 Day 1 post lenalidomide dose)
- Titers of ADAs Against Belantamab Mafodotin(Up to approximately 4.5 years)
- Number of Participants With Worse Grade Post-baseline Punctate Keratopathy Findings(Baseline (Day 1) and up to approximately 4.5 years)
- Number of Participants With Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin(Up to approximately 4.5 years (End of Treatment [EoT]))
- Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) Overall Composite Scores(Baseline (Day 1) and up to approximately 4.5 years)
- Number of Participants With AEs of Special Interest (AESI)(Up to approximately 4.5 years)
- Number of Participants With Worst-case Change From Baseline in Best Corrected Visual Acuity Test (BCVA) Scores(Baseline (Day 1) and up to approximately 4.5 years)
- Number of Participants With Post-baseline Decline in BCVA to Light Perception or no Light Perception(Baseline (Day 1) and up to approximately 4.5 years)
- 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 up to approximately 4.5 years (End of treatment [EoT]))
- Change From Baseline in Ocular Surface Disease Index (OSDI) Total Scores(Baseline (Day 1) and up to approximately 4.5 years)
- Number of Participants With Symptomatic AEs Measured by Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)(Up to approximately 4.5 years)
- Number of Participants With Worst-case Post-baseline Change in BCVA Scores by Snellen Results(Baseline (Day 1) and up to approximately 4.5 years)
- Number of Participants With Shift in Corneal Epithelium Findings From no (Baseline) to Yes (Worst Post-Baseline)(Baseline (Day 1) and up to approximately 4.5 years)
- Change From Baseline in EORTC QLQ 20-item Multiple Myeloma Module (MY20) Score(Baseline (Day 1) and up to approximately 4.5 years (End of treatment [EoT]))