NCT05714839
招募中
1 期
A Phase 1/2 Open-label, Multicentre, Dose Escalation and Expansion Study to Investigate the Safety, Tolerability, and Clinical Activity of Belantamab as Monotherapy and in Combination With Other Treatments in Participants With Multiple Myeloma
概览
- 阶段
- 1 期
- 干预措施
- Unconjugated belantamab antibody
- 疾病 / 适应症
- Multiple Myeloma
- 发起方
- GlaxoSmithKline
- 入组人数
- 153
- 试验地点
- 27
- 主要终点
- Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)
- 状态
- 招募中
- 最后更新
- 3个月前
概览
简要总结
The study consists of three parts:
- Part 1 The primary purpose of this part aims to evaluate the safety, tolerability, and clinical activity of escalating doses of single agent Unconjugated belantamab antibody in participants with refractory multiple myeloma (RRMM) who have received at least 3 prior therapies (4L+).
- Part 2 The primary purpose of this part is to evaluate the safety, tolerability, and clinical activity of different dose ratios of belantamab mafodotin in combination with Unconjugated belantamab antibody (delivered as separate drugs) in participants with RRMM who have received at least 3 prior therapies (4L+).
- Part 3: The Primary purpose of this part will evaluate the clinical activity of a selected dose of the unconjugated belantamab antibody, either alone or in combination with belantamab mafodotin alongside the standard of care (SoC) pomalidomide-dexamethasone backbone. The study will focus on patients with multiple myeloma who have undergone at least one prior line of therapy, including treatment with lenalidomide.
研究者
入排标准
入选标准
- •Participants at the time of signing the Informed Consent Form (ICF) are at least 18 years old or are of the legal age of consent in the jurisdiction in which the study is taking place.
- •Participants who have histologically or cytologically confirmed diagnosis of Multiple Myeloma (MM), as defined by the international myeloma working group (IMWG) and have progressed on or following the last line of treatment Part 1 and Part 2: Participants who have received at least 3 prior lines of anti-myeloma treatments, , including lenalidomide, a proteasome inhibitor, and an anti-CD38 mAb either in combination or separately.
- •Part 3: Have received at least 1 prior line of treatment anti-myeloma treatments, including lenalidomide. Prior anti-CD38-containing regimen is not mandated, however no more than 70% of participants recruited may be anti-CD38 naïve
- •Participants with a history of Autologous stem cell transplant (ASCT) are eligible for study participation provided the following eligibility criteria are met:
- •Transplant was greater than (\>)100 days prior to screening.
- •No active bacterial, viral, or fungal infection(s) present
- •Eastern cooperative oncology group-performance status (ECOG-PS) of 0 to
- •Measurable disease defined as at least ONE of the following:
- •Serum M-protein concentration greater than (\>=) 0.5 gram (g)/ deciliter (dL) (\>=5 gram/liter \[g/L\])
- •Urine M-protein excretion \>=200 milligram(mg)/24 hours (\>=0.2 g/24 hours)
排除标准
- •Diagnosis of primary Amyloid Light chain (AL) Amyloidosis, active Polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes (POEMS) syndrome, primary plasma cell leukemia.
- •Part 3: Active or history of venous or arterial thromboembolism within the past 3 months. Contraindications to or unwilling to undergo protocol-required anti-thrombotic prophylaxis
- •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.
- •Participant is exhibiting signs of meningeal or central nervous system involvement with MM.
- •Current corneal epithelial disease except nonconfluent Superficial punctate keratitis (SPK).
- •Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice.
- •Presence of 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 investigator (PI) and GlaxoSmithKline (GSK) Medical Director, will not affect the evaluation of the effects of this clinical trial treatment on the currently targeted malignancy (MM).Participants on active surveillance or hormone treatment for non-metastatic prostate cancer are not excluded. Participants on hormone therapy for non-metastatic breast cancer are not excluded
- •Evidence of cardiovascular risk including any of the following:
- •Evidence of current clinically significant untreated arrhythmias, including, but not limited to, clinically significant Electrocardiogram (ECG) abnormalities such as 2nd degree (Mobitz Type II) or 3rd degree Atrioventricular (AV) block.
- •Part 1 dose escalation and Part 2 only: QT interval corrected using Fridericia's formula (QTcF) interval \>480 millisecond(msec) (QT interval corrected for heart rate according to Fridericia's formula), and/or hypokalemia, and/or family history of long QT syndrome.
研究组 & 干预措施
Part 1: Dose escalation and expansion of the unconjugated belantamab antibody monotherapy
Unconjugated belantamab antibody will be administered in participants with RRMM until progressive disease (PD)
干预措施: Unconjugated belantamab antibody
Part 2:Unconjugated belantamab antibody and belantamab mafodotin-given separately dose range finding
Participants with RRMM will receive unconjugated belantamab antibody and belantamab mafodotin
干预措施: Unconjugated belantamab antibody and belantamab mafodotin
Part 3: Unconjugated belantamab +/- belantamab mafodotin +pomalidomide/dexamethasone in 2L+ RRMM
Participants with second line (2L+) RRMM will receive Unconjugated belantamab antibody in combination with pomalidomide-dexamethasone backbone, with or without belantamab mafodotin.
干预措施: Unconjugated belantamab antibody in combination with pomalidomide-dexamethasone backbone, with or without belantamab mafodotin
Part 1b:Optional belantamab mafodotin
Participants enrolled in Part 1 and Part 2 will be dosed until PD after which they will have the option to receive treatment with single agent belantamab mafodotin.
干预措施: Belantamab mafodotin
结局指标
主要结局
Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)
时间窗: Cycle 1 (Each cycle is of 28 days)
Part 2: Overall Response Rate (ORR)
时间窗: Up to 52 months
Part 1, 2 and 3: Number of Participants with any Adverse Event
时间窗: Up to 52 months
Part 1, 2and 3: Number of Participants with Worst Case Grade Change from Baseline in Laboratory and Vital Sign Parameters
时间窗: Up to 52 months
Part 1, 2 and 3: Number of Participants with severity of ocular events by the Keratopathy Visual Acuity (KVA) scale
时间窗: Up to 52 months
Part 3: Very Good Partial Response and better rate (VGPR+)
时间窗: Up to 52 months
VGPR+ is defined as the percentage of participants with a confirmed VGPR or better (i.e., VGPR, complete response, stringent complete response)
次要结局
- Part 1: Observed Plasma Concentration of belantamab(Up to 52 months)
- Part 1: Area Under the Curve (AUC) of belantamab(Up to 52 months)
- Part 1: Maximum Concentration (Cmax) of belantamab(Up to 52 months)
- Part 1: Number of Participants with Anti-Drug Antibodies (ADA) against belantamab(Up to 52 months)
- Part 1: Titers of ADA against belantamab(Up to 52 months)
- Part 1: Overall Response Rate (ORR)(Up to 52 months)
- Part 2: Duration of Response (DoR)(Up to 52 months)
- Part 2: Observed Plasma Concentration of Total belantamab(Up to 52 months)
- Part 2: Area Under the Curve (AUC) of Total belantamab(Up to 52 months)
- Part 1: Maximum Concentration (Cmax) of Total belantamab(Up to 52 months)
- Part 2: Area Under the Curve (AUC) of belantamab mafodotin (ADC)(Up to 52 months)
- Part 2: Observed Plasma Concentration of Cys-Monomethyl Auristatin-F (Cys-mcMMAF)(Up to 52 months)
- Part 2: Area Under the Curve (AUC) of Cys-mcMMAF(Up to 52 months)
- Part 2: Observed Plasma Concentration of belantamab mafodotin (ADC)(Up to 52 months)
- Part 2: Maximum Concentration (Cmax) of belantamab mafodotin (ADC)(Up to 52 months)
- Part 2: Maximum Concentration (Cmax) of Cys-mcMMAF(Up to 52 months)
- Part 2: Number of Participants with ADAs against Unconjugated belantamab antibody and belantamab mafodotin(Up to 52 months)
- Part 2: Titers of ADAs against Unconjugated belantamab antibody and belantamab mafodotin(Up to 52 months)
- Part 3: Minimal residual disease (MRD) negativity rate in participants achieving at least VGPR(Up to 52 months)
- Part 3: Overall Response Rate (ORR)(Up to 52 months)
- Part 3: Duration Of Response (DoR)(Up to 52 months)
- Part 3: Observed Plasma Concentration of Total belantamab(Up to 52 months)
- Part 3: Area Under the Curve (AUC) of Total belantamab(Up to 52 months)
- Part 3: Observed Plasma Concentration of belantamab mafodotin (ADC)(Up to 52 months)
- Part 3: Area Under the Curve (AUC) of belantamab mafodotin (ADC)(Up to 52 months)
- Part 3: Maximum Concentration (Cmax) of belantamab mafodotin (ADC)(Up to 52 months)
- Part 3: Observed Plasma Concentration of Cys-Monomethyl Auristatin-F (Cys-mcMMAF)(Up to 52 months)
- Part 3: Area Under the Curve (AUC) of Cys-mcMMAF(Up to 52 months)
- Part 3: Maximum Concentration (Cmax) of Cys-mcMMAF(Up to 52 months)
- Part 3: Number of Participants with ADAs against Unconjugated belantamab antibody and belantamab mafodotin(Up to 52 months)
- Part 3: Titers of ADAs against Unconjugated belantamab antibody and belantamab mafodotin(Up to 52 months)
研究点 (27)
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