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临床试验/NCT04177823
NCT04177823已完成1 期

A Phase I Open-label, Dose Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Clinical Activity of the Antibody Drug Conjugate GSK2857916 in Chinese Participants With Relapsed/Refractory Multiple Myeloma Who Have Failed At Least Two Lines of Previous Treatment, Containing an Alkylator, a Proteasome Inhibitor and an Immunomodulatory Agent

GlaxoSmithKline1 个研究点 分布在 1 个国家目标入组 6 人开始时间: 2019年12月9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
1 期
状态
已完成
入组人数
6
试验地点
1
主要终点
Number of Participants With Adverse Events (AEs)
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 a neoplastic plasma cell disorder that is characterized by osteolytic bone lesions, anemia, hypercalcemia and renal failure. belantamab mafodotin was well tolerated in previous studies with at least one dose of belantamab mafodotin in heavily pre-treated participants with relapsed/refractory multiple myeloma (RRMM). This aim of the study is to explore safety, pharmacokinetics (PK), tolerability, immunogenicity and clinical activity of belantamab mafodotin monotherapy in Chinese participants with RRMM who have received at least 2 prior line of anti-myeloma therapy including an alkylator, a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD). This study will include two dose cohorts 2.5 milligram per kilogram (mg/kg) and 3.4 mg/kg. A maximum of 12 participants will be enrolled, 6 each for 2.5 mg/kg cohort and 3.4 mg/kg cohort based on 3+3 design. Participants will be treated until disease progression, intolerable toxicity, end of study or informed consent withdrawal.

研究设计

研究类型
Interventional
分配方式
Non Randomized
干预模型
Single Group
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

  • •Provide signed written informed consent, which includes compliance with requirements and restrictions listed in the consent form.
  • •Male or female, 18 years or older (at the time consent is obtained).
  • •Eastern Cooper Oncology Group (ECOG) performance status of 0-
  • •Histological or cytologically confirmed diagnosis of MM as defined according to IMWG criteria and a) Has undergone stem cell transplant or transplant is considered not feasible by local assessment, b) Has failed at least 2 prior lines of anti-myeloma treatments, containing all of the following classes of drugs: alkylating agent, IMID and PI, c) In addition, eligible participant needs to be refractory to an IMiD (i.e.,lenalidomide or pomalidomide), and to a proteasome inhibitor (i.e., bortezomib, ixazomib or carfizomib) as defined by International Myeloma Working Group (IMWG) criteria, d) Participants who failed with cluster of differentiation38 (CD38) antibody (i.e., daratumumab) in previous clinical trials can also be considered to include if they meet the remainder of inclusion criteria in this protocol.
  • •Has measurable disease with at least one of the following: a) Serum M-protein greater than or equal to 0.5 grams per deciliter (g/dL) (5 g/L) , b) Urine M-protein greater than or equal to 200 mg/24hour, c) Serum Free light chain (FLC) assay: Involved FLC level greater than or equal to10 mg/dL (greater than or equal to 100 mg/L) and an abnormal serum free light chain ratio (less than 0.26 or greater than 1.65)
  • •Participants with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met: a) Transplant was greater than 100 days prior to study enrolment, b) No active infection(s), c) Participant meets the remainder of the eligibility criteria outlined in this protocol.
  • •Adequate organ system functions.
  • •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 at least one of the following conditions applies: Is 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 less than 1 percent 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, 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: Agree to use a male condom and female partner to use an additional highly effective contraceptive method with a failure rate of less than 1 percent per year as when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.
  • •All prior treatment-related toxicities (defined by National Cancer Institute-Common Toxicity 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 and Grade 2 peripheral neuropathy.

排除标准

  • •Systemic anti-myeloma therapy within less than 14 days, or plasmapheresis within 7 days prior to the first dose of study drug.
  • •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 (SCT).
  • •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, provided they fulfil 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 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 GSK Medical Monitor, will not affect the evaluation of the effects of this clinical trial treatment on the currently targeted malignancy (MM).
  • •Evidence of cardiovascular risk including any of the following: a) corrected QT internal Fridericia (QTcF) interval greater than equal to 480 milliseconds (msecs), b) Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Mobitz Type II) or 3rd degree atrioventricular (AV) block, c) History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within three months of Screening, d) Class III or IV heart failure as defined by the New York Heart Association functional classification system, e) Uncontrolled severe hypertension, e.g. 170/
  • •Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to belantamab mafodotin, or any of the components of the study intervention.
  • •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 intervention).
  • •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 intervention.

研究组 & 干预措施

Chinese participants with relapsed/refractory multiple myeloma

Experimental

Participants will be administered belantamab mafodotin 2.5 mg/kg or 3.4 mg/kg as an intravenous infusion on Day 1 of each 21-day cycle over 30 minutes. Participants will be treated until disease progression, intolerable toxicity, end of study or informed consent withdrawal.

干预措施: Belantamab mafodotin (Drug)

结局指标

主要结局

Number of Participants With Adverse Events (AEs)

时间窗: Up to 24 months and 21 days

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.

Number of Participants With Serious Adverse Events (SAEs)

时间窗: Up to 24 months and 21 days

An 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; is a congenital anomaly/birth defect; important medical events that may jeopardize the participant or may require medical or surgical intervention; is associated with liver injury and impaired liver function.

Number of Participants With Dose Limited Toxicities (DLTs)

时间窗: Day 1 to day 21 of cycle 1

An event was considered DLT if it occurred within 21 days of treatment and met any of the following criteria within same period: * Any Grade (Gr.) 3 or greater non-hematologic toxicity as described in NCI-CTCAE Version 5.0, other than corneal events that persists for \>48 hours despite supportive treatment or leads to hospitalization. * Hematologic toxicity such as Gr. 3 or greater febrile neutropenia lasting \>48 hours despite adequate treatment (Gr. 3 defined as absolute neutrophil count (ANC) \<1000/millimeter cube (mm\^3) at a single temperature \>38.3 degree celsius or a sustained temperature \>=38 degree celsius for more than 1 hour) and, Gr. 4 thrombocytopenia defined as platelet count \<25000/mm\^3 with clinically significant bleeding, or if platelet transfusion is required. * Gr. 4 per the corneal grading scale. * Liver toxicity meeting pre-specified by GSK liver stopping criteria.

次要结局

  • AUC[0-t] of Belantamab Mafodotin Total Antibody(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • AUC[0-t] of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF)(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on Day 1, anytime on Day 2, 4, 8, 15 and 22 of Cycle 1 (each cycle is of 21 days))
  • AUC[0-infinity] of Belantamab Mafodotin Total Antibody(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • Observed Plasma Concentration at the End of Infusion (CEOI) of Belantamab Mafodotin Antibody-drug Conjugate (ADC)(Pre-dose (within 30 minutes prior to start of infusion) on day 1 of cycle 2, 4, 6, 9 and 12 (each cycle is of 21 days))
  • CEOI of Belantamab Mafodotin Total Antibody(Pre-dose (within 30 minutes prior to start of infusion) on day 1 of cycle 2, 4, 6, 9 and 12 (each cycle is of 21 days))
  • CL of Belantamab Mafodotin Total Antibody(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • AUC[0-infinity] of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF)(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on Day 1, anytime on Day 2, 4, 8, 15 and 22 of Cycle 1 (each cycle is of 21 days))
  • CEOI of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF)(Pre-dose (within 30 minutes prior to start of infusion) on day 1 of cycle 2, 4, 6, 9 and 12 (each cycle is of 21 days))
  • Cmax of Belantamab Mafodotin Total Antibody(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on Day 1, anytime on Day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • Time to Reach Maximum Observed Concentration (Tmax) of Belantamab Mafodotin Antibody-drug Conjugate (ADC)(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • Tmax of Belantamab Mafodotin Total Antibody(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC[0-t]) of Belantamab Mafodotin Antibody-drug Conjugate (ADC)(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • AUC[0-tau] of Belantamab Mafodotin Total Antibody(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • Tlast of Belantamab Mafodotin Total Antibody(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • Systemic Clearance (CL) of Belantamab Mafodotin Antibody-drug Conjugate (ADC)(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • Systemic Clearance Normalized by Body Weight (CL/Weight) of Belantamab Mafodotin Antibody-drug Conjugate (ADC)(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • Vss of Belantamab Mafodotin Total Antibody(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • Area Under the Concentration-time Curve During the Dosing Interval (AUC[0-tau]) of Belantamab Mafodotin Antibody-drug Conjugate (ADC)(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on Day 1, anytime on Day 2, 4, 8, 15 and 22 of Cycle 1 (each cycle is of 21 days))
  • Area Under the Concentration-time Curve From Time 0 to 168h (AUC[0-168]) of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF)(Up to 168 hours)
  • Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0-infinity]) of Belantamab Mafodotin Antibody-drug Conjugate (ADC)(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • Maximum Observed Concentration (Cmax) of Belantamab Mafodotin Antibody-drug Conjugate (ADC)(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • Tlast of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF)(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • CL/Weight of Belantamab Mafodotin Total Antibody(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on Day 1, anytime on Day 2, 4, 8, 15 and 22 of Cycle 1 (each cycle is of 21 days))
  • Vss/Weight of Belantamab Mafodotin Total Antibody(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • Apparent Terminal Half-life (t1/2) of Belantamab Mafodotin Antibody-drug Conjugate (ADC)(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • Cmax of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF)(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on Day 1, anytime on Day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • Tmax of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF)(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast) of Belantamab Mafodotin Antibody-drug Conjugate (ADC)(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • Volume of Distribution at Steady State (Vss) of Belantamab Mafodotin Antibody-drug Conjugate (ADC)(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • Volume of Distribution at Steady State Normalized by Body Weight (Vss/Weight) of Belantamab Mafodotin Antibody-drug Conjugate (ADC)(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • t1/2 of Belantamab Mafodotin Total Antibody(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • t1/2 of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF)(Pre-dose (within 30 minutes prior to start of infusion), end of infusion (EOI), 2, 4, 8 and 24 hours post start of infusion (HPS) on day 1, anytime on day 2, 4, 8, 15 and 22 of cycle 1 (each cycle is of 21 days))
  • Trough Concentration Prior to the Next Dose for Each Cycle (Ctrough) of Belantamab Mafodotin Antibody-drug Conjugate (ADC)(Pre-dose (within 30 minutes prior to start of infusion) on day 1 of cycle 1, 3, 5, 8 and 11 (each cycle is of 21 days))
  • Ctrough of Belantamab Mafodotin Total Antibody(Pre-dose (within 30 minutes prior to start of infusion) on day 1 of cycle 1, 3, 5, 8 and 11 (each cycle is of 21 days))
  • Number of Participants With Abnormal Vital Signs(Up to 21 months)
  • Percentage of Participants With Objective Response Rate (ORR)(Up to 21 months)
  • Titers of ADAs Against Belantamab Mafodotin(Up to 24 months and 21 days)
  • Number of Participants With Worst- Case Grade Changes Post-baseline in Hematology Parameter: Hemoglobin, Lymphocytes, Neutrophils, Platelets, Leukocytes(Baseline (day 1) and up to 21 months)
  • Number of Participants With Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin(Up to 24 months and 21 days)
  • Number of Participants With Worst- Case Grade Changes Post-baseline in Clinical Chemistry Parameters(Baseline (day 1) and up to 21 months)
  • Change From Baseline in Ocular Surface Disease Index (OSDI) Total Score(Baseline (day 1) Up to 24 months and 21 days)

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (1)

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