A Study of Belantamab Mafodotin Monotherapy in Multiple Myeloma Participants With Normal and Varying Degree of Impaired Renal Function

NCT04398745 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 209626
• Study Type: interventional
• Target: 36
• Locations: 4 countries
• Sites: 19

Brief Summary

Belantamab mafodotin is an antibody-drug conjugate (ADC) containing humanized anti- B-cell maturation antigen (BCMA) monoclonal antibody (mAb). Renal impairment is a major complication of multiple myeloma (MM) and the majority of MM participants is either at risk or already has renal dysfunction at initial diagnosis. The purpose of this study is to assess the pharmacokinetics (PK), safety, and tolerability of belantamab mafodotin monotherapy in participants with RRMM, who have had at least 3 lines of prior treatment (or at least 2 lines of prior treatment if ineligible for autologous stem cell transplantation ) and have either normal or impaired renal functions. The study will consist of two parts: part 1 will include participants with normal/mildly impaired renal function and severe renal impairment and part 2 will include participants with end-stage renal disease (ESRD), where participants are either not undergoing or require hemodialysis. Participants will be administered belantamab mafodotin at a dose of 2.5 milligram per kilogram (mg/kg) intravenously once in three weeks (Q3W) dosing in Part 1. Based on the Part 1 Safety/Pharmacokinetic (PK) data, Part 2 participants will be administered the dose of either 2.5 mg/kg or 1.9 mg/kg (or other adjusted dose). Participants will be treated with belantamab mafodotin monotherapy until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first. This study will include a screening phase, treatment phase, follow-up phase and a post analysis continued treatment (PACT) phase . The total duration of the study is approximately up to 48 months.

Conditions

Multiple Myeloma

Keywords

DREAMM12; End-stage renal disease; Normal renal function; Renal impairment; Relapsed and/or refractory multiple myeloma; Belantamab mafodotin

Outcome Measures

Primary Outcomes (34)

• Part 1: Maximum observed plasma concentration (Cmax) of GSK2857916

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

• Part 1: Time to Cmax (Tmax) of GSK2857916

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

• Part 1: Concentration of GSK2857916 at the end of infusion (C-EOI)

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Cycle 1 up to Cycle 3: end infusion (EOI) (each cycle is 21 days)

• Part 1: Predose plasma concentration (Ctrough) of GSK2857916

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Predose on Cycle 1 and up to Cycle 3 (each cycle is 21 days)

• Part 1: AUC over the dosing interval (AUC[0-tau]) of GSK2857916

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

• Part 1: Last time point where the concentration is above the limit of quantification (Tlast) of GSK2857916

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

• Part 1: Cmax of total monoclonal antibody (mAb)

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

• Part 1: Tmax of total mAb

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

• Part 1: Ctrough of total mAb

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Predose on Cycle 1 and up to Cycle 3 (each cycle is 21 days)

• Part 1: C-EOI of total mAb

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Cycle 1 up to Cycle 3: end infusion (EOI) (each cycle is 21 days)

• Part 1: AUC(0-tau) of total mAb

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

• Part 1: Tlast of total mAb

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

• Part 1: Cmax of Cys Monomethyl Auristatin F (cys-mcMMAF)

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

• Part 1: Tmax of cys-mcMMAF

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

• Part 1: C-EOI of cys-mcMMAF

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Cycle 1 up to Cycle 3: end infusion (EOI) (each cycle is 21 days)

• Part 1: AUC(0-168 hours) of cys-mcMMAF

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Predose and up to 168 hours

• Part 1: Tlast of cys-mcMMAF

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

• Part 2: Cmax of GSK2857916

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

• Part 2: Tmax of GSK2857916

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

• Part 2: C-EOI of GSK2857916

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Cycle 1 up to Cycle 3: end infusion (EOI) (each cycle is 21 days)

• Part 2: Ctrough of GSK2857916

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Predose on Cycle 1 and up to Cycle 3 (each cycle is 21 days)

• Part 2: AUC(0-tau) of GSK2857916

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

• Part 2: Tlast of GSK2857916

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

• Part 2: Cmax of total mAb

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

• Part 2: Tmax of total mAb

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

• Part 2: C-EOI of mAb

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Cycle 1 up to Cycle 3: end infusion (EOI) (each cycle is 21 days)

• Part 2: Ctrough of total mAb

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Predose on Cycle 1 up to Cycle 3 (each cycle is 21 days)

• Part 2: AUC(0-tau) of total mAb

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

• Part 2: Tlast of total mAb

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

• Part 2: Cmax of cys-mcMMAF

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

• Part 2: Tmax of cys-mcMMAF

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

• Part 2: C-EOI of cys-mcMMAF

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Cycle 1 up to Cycle 3: end infusion (EOI) (each cycle is 21 days)

• Part 2: AUC(0-168 hours) of cys-mcMMAF

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Predose and up to 168 hours

• Part 2: Tlast of cys-mcMMAF

  Blood samples will be collected at indicated time points for pharmacokinetic analysis.

  Up to Day 85

Secondary Outcomes (5)

• Part 1 and Part 2: Change from Baseline in Vital Signs- Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) (millimeter of mercury [mmHg])

  Baseline and up to 48 months

• Part 1 and Part 2: Change from Baseline in Vital Sign- Heart rate (beats per minute)

  Baseline and up to 48 months

• Part 1 and Part 2: Number of participants with adverse events (AEs) and serious adverse events (SAEs)

  Up to 48 months

• Part 1 and Part 2: Number of participants with toxicity grading for clinical laboratory parameters

  Up to 48 months

• Part 1 and Part 2: Change from baseline in physical examination parameter

  Baseline and up to 48 months

Study Arms (4)

Part 1: Participants with normal/mild impaired renal function

EXPERIMENTAL

Participants with normal or mildly impaired renal function (Normal: individual glomerular filtration rate \[iGFR\]: \>=90 milliliter per minute; Mild impairment: iGFR: 60-89 mL/min will be administered with belantamab mafodotin 2.5 mg/kg as an intravenous infusion over 30 minutes Q3W on Day 1 of every 21- day cycle until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first.

Drug: Belantamab mafodotin

Part 1: Participants with severe renal impairment

EXPERIMENTAL

Participants with severely impaired renal function (iGFR: 15-29 mL/min) will be administered with belantamab mafodotin 2.5 mg/kg as an intravenous infusion over 30 minutes Q3W on Day 1 of every 21- day cycle until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first.

Drug: Belantamab mafodotin

Part 2: Participants with ESRD (not on dialysis)

EXPERIMENTAL

Participants with ESRD (iGFR: \<15 mL/min) not on dialysis will be administered with belantamab mafodotin either 2.5 mg/kg or 1.9 mg/kg (or other adjusted dose) as an intravenous infusion over 30 minutes Q3W on Day 1 of every 21- day cycle until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first. In Part 2, the dose will be decided after evaluation of pharmacokinetic and safety data of Part 1.

Drug: Belantamab mafodotin

Part 2: Participants with ESRD (on hemodialysis)

EXPERIMENTAL

Participants with ESRD (iGFR: \<15 mL/min) on hemodialysis will be administered with belantamab mafodotin either 2.5 mg/kg or 1.9 mg/kg (or other adjusted dose) as an intravenous infusion over 30 minutes Q3W on Day 1 of every 21-day cycle until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first. In Part 2, the dose will be decided after evaluation of pharmacokinetic and safety data of Part 1.

Drug: Belantamab mafodotin

Interventions

Belantamab mafodotin DRUG

Belantamab mafodotin will be provided as lyophilized powder which will be available as 100 milligrams per vial (mg/vial) in single-use vial for reconstitution. Lyophilized belantamab mafodotin will reconstituted using water for injection, dilute with normal 0.9 % saline before use.

Also known as: GSK2857916

Part 1: Participants with normal/mild impaired renal function; Part 1: Participants with severe renal impairment; Part 2: Participants with ESRD (not on dialysis); Part 2: Participants with ESRD (on hemodialysis)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the Informed Consent Form.
• Male and/or female participants must be 18 years of age or older, at the time of signing the informed consent. In Republic of Korea, participants must be 19 years of age or older at the time of signing informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Participants with histologically or cytologically confirmed diagnosis of MM, as defined in International Myeloma Working Group criteria: 1. Has undergone autologous stem cell transplant (SCT) or is considered transplant-ineligible; 2. Has failed at least 2 prior lines of anti-myeloma treatments, including an immunomodulatory drug (example \[e.g.\], lenalidomide or pomalidomide) and a proteasome inhibitor (e.g., bortezomib, ixazomib or carfilzomib). In Republic of Korea, participants should also have relapsed or refractory disease after treatment with an anti-CD38 antibody, if accessible to patients, or other suitable local standard of care.
• Participants have measurable disease with at least one of the following: Serum M-protein \>=0.5 grams per deciliter (g/dL) (\>=5 grams per liter \[g/L\]); Urine M-protein \>=200 milligrams (mg) per 24 hours (mg/24 h); and Serum free light chain (FLC) assay: Involved FLC level \>=10 milligrams per deciliter (mg/dL) (\>=100 milligrams per liter \[mg/L\]) 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: 1. Transplant was \>100 days prior to study enrollment, 2. No active infection(s), and 3. Participant meets the remainder of the eligibility criteria outlined in this protocol.
• Participants with adequate organ system functions as defined follows: Absolute neutrophil count \>=1.0 x 10\^9 per liter (/L); Hemoglobin \>=7.0 g/dL or 4.9 millimoles per liter (mmol/L); Platelets \>= 50 x 10\^9/L; Total bilirubin \<=1.5 x Upper limit of normal (ULN) (Isolated bilirubin \>=1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent \[%\]); Alanine aminotransferase \<=2.5 x ULN; iGFR, Group 1: normal/ mildly impaired \>=60milliliter per minute (mL/min); Group 2: severe 15-29 mL/min; Group 3: ESRD (not on dialysis) \<15 mL/min; Group 4: ESRD (on dialysis) \<15 mL/min; and left ventricular ejection fraction by echocardiograms \>=40%.
• Male participants: Contraceptive use by men 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 from the time of first dose of study until 6 months after the last dose of study treatment to allow for clearance of any altered sperm: 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 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 as when having sexual intercourse with a WOCBP (including pregnant females).

You may not qualify if:

• Participants with active plasma cell leukemia at the time of screening. Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, myeloma protein and skin changes), Waldenstroem Macroglobulinemia
• Participants had a prior allogeneic stem cell transplant. . Participants who have undergone a syngeneic bone marrow transplant will be allowed only if there is no history of, or no currently active graft-versus-host-diseases (GvHD).
• Participant has received an investigational drug within 14 days or 5 half-lives whichever is shorter, preceding the first dose of study drug. This includes prior treatment with a monoclonal antibody. The only exception is emergency use of a short course of systemic corticosteroids (equivalent to, or less than: dexamethasone 40 milligrams per day \[mg/day\] for a maximum of 4 days) before treatment.
• Prior belantamab mafodotin therapy.
• Participant has received a strong Organic-anion transporting polypeptide inhibitor within 14 days or 5 half-lives, whichever is shorter, preceding the first dose of study drug.
• Systemic active infection requiring treatment.
• Any unresolved toxicity \>=Grade 2 from previous treatment except for alopecia, or peripheral neuropathy up to Grade 2.
• Plasmapheresis within 7 days prior to the first dose of study drug. Screening laboratory values must be performed after last plasmapheresis.
• Any major surgery within the last 4 weeks prior to Day 1 of Screening.
• Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities except renal impairment) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures.
• Evidence of active mucosal or internal bleeding.
• 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. (Stable chronic liver disease \[(including Gilbert's syndrome or asymptomatic gallstones\]) or hepatobiliary involvement of malignancy is acceptable if participant otherwise meets entry criteria)
• Participants with previous or concurrent malignancies other than MM are excluded, unless the prior 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. (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 untreated arrhythmias, including clinically significant electrocardiogram abnormalities such as second degree (Mobitz Type II) or third degree atrioventricular block; History of myocardial infarction (within prior 18 months), 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 and 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (19)

GSK Investigational Site

Tucson, Arizona, 85724, United States

Location

GSK Investigational Site

Beverly Hills, California, 90211, United States

Location

GSK Investigational Site

Sacramento, California, 95817, United States

Location

GSK Investigational Site

Jacksonville, Florida, 32224-3899, United States

Location

GSK Investigational Site

Plantation, Florida, 33322, United States

Location

GSK Investigational Site

Chicago, Illinois, 60611, United States

Location

GSK Investigational Site

Westwood, Kansas, 66205, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21201-1595, United States

Location

GSK Investigational Site

Chapel Hill, North Carolina, 27514, United States

Location

GSK Investigational Site

Portland, Oregon, 97239, United States

Location

GSK Investigational Site

The Woodlands, Texas, 77380, United States

Location

GSK Investigational Site

Athens, 10676, Greece

Location

GSK Investigational Site

Athens, 11528, Greece

Location

GSK Investigational Site

Singapore, 119228, Singapore

Location

GSK Investigational Site

Singapore, 169856, Singapore

Location

GSK Investigational Site

Busan, 49241, South Korea

Location

GSK Investigational Site

Incheon, 21565, South Korea

Location

GSK Investigational Site

Seoul, 06351, South Korea

Location

GSK Investigational Site

Seoul, 06591, South Korea

Location

MeSH Terms

Conditions

Multiple Myeloma; Kidney Failure, Chronic; Renal Insufficiency

Interventions

belantamab mafodotin

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Renal Insufficiency, Chronic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: May 19, 2020
• First Posted: May 21, 2020
• Study Start: October 9, 2020
• Primary Completion: April 21, 2025
• Study Completion: December 31, 2025
• Last Updated: May 23, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

SG (2); GR (2); KR (4); US (11)