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

Multiple Myeloma Clinical Trial

— DREAMM12  

Official title:

A Phase I Study to Evaluate the Pharmacokinetics and Safety of Belantamab Mafodotin Monotherapy in Participants With Relapsed and/or Refractory Multiple Myeloma (RRMM) Who Have Normal and Varying Degrees of Impaired Renal Function (DREAMM 12)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04398745
• Other study ID #: 209626
• Status: Recruiting
• Phase: Phase 1
• Start date: October 9, 2020
• Est. completion date: March 7, 2025

Study information

• Verified date: October 2022
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: March 7, 2025
• Est. primary completion date: March 7, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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%.
• Main additional inclusion criteria in Group 1 (matched control participants): Matched to at least one severely renal impaired participant by Baseline body weight (+/-20%) and Baseline albumin levels (+/-10%).
• Female participants: Contraceptive use by 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 <1% per year), preferably with low user dependency, during the intervention period and for at least 4 months 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 within 72 hours of dosing on Cycle 1 Day 1 and agree to use highly effective contraception during the study and for 4 months after the last dose of study medication. 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 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).

Exclusion Criteria:

• 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.
• Known human immunodeficiency virus infection, unless the participant can meet all of the following criteria: Established anti-retroviral therapy (ART) for at least 4 weeks and HIV viral load <400 copies/mL prior to first dose; CD4+ T-cell (CD4+) counts =350 cells/ L and no history of AIDS-defining opportunistic infections within the last 12 months
• Participants with Hepatitis B will be excluded unless the following criteria can be met: If the participant is hepatitis B core antibody (HbcAb) positive or hepatitis B surface antigen (HbsAg) negative, then hepatitis B virus (HBV) deoxyribonucleic acid (DNA) should be undectectable at the time of screening; If HbsAg+ at screening or <=3 months prior to first dose of study treatment, then HBV DNA should be undetectable, highly effective antiviral treatment should be started =4 weeks prior to first dose of study treatment. Participants with cirrhosis are excluded.
• Positive hepatitis C antibody test result or positive hepatitis C ribonucleic acid test result at Screening or within 3 months prior to first dose of study treatment unless the participant can meet the following criteria: RNA test negative and Successful anti-viral treatment (usually 8 weeks duration) is required, followed by a negative HCV RNA test after a washout period of at least 4 weeks prior to first dose.
• Participants with renal impairment due to hepatic disease (hepatorenal syndrome).
• Current corneal epithelial disease except for mild punctuate keratopathy.
• Participant is a woman who is pregnant or breastfeeding.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Renal Insufficiency

Intervention

Drug:
• Belantamab mafodotin
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.

Locations

Country	Name	City	State
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Korea, Republic of	GSK Investigational Site	Busan
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Singapore	GSK Investigational Site	Singapore
Singapore	GSK Investigational Site	Singapore
United States	GSK Investigational Site	Ann Arbor	Michigan
United States	GSK Investigational Site	Baltimore	Maryland
United States	GSK Investigational Site	Beverly Hills	California
United States	GSK Investigational Site	Chapel Hill	North Carolina
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Hackensack	New Jersey
United States	GSK Investigational Site	Jacksonville	Florida
United States	GSK Investigational Site	Manhasset	New York
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Plantation	Florida
United States	GSK Investigational Site	Portland	Oregon
United States	GSK Investigational Site	Rockledge	Pennsylvania
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	Sioux Falls	South Dakota
United States	GSK Investigational Site	Stony Brook	New York
United States	GSK Investigational Site	The Woodlands	Texas
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Greece,  Korea, Republic of,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Part 1: Time to Cmax (Tmax) of GSK2857916	Blood samples will be collected at indicated time points for pharmacokinetic analysis.	Up to Day 85
Primary	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)
Primary	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)
Primary	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
Primary	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
Primary	Part 1: Cmax of total monoclonal antibody (mAb)	Blood samples will be collected at indicated time points for pharmacokinetic analysis.	Up to Day 85
Primary	Part 1: Tmax of total mAb	Blood samples will be collected at indicated time points for pharmacokinetic analysis.	Up to Day 85
Primary	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)
Primary	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)
Primary	Part 1: AUC(0-tau) of total mAb	Blood samples will be collected at indicated time points for pharmacokinetic analysis.	Up to Day 85
Primary	Part 1: Tlast of total mAb	Blood samples will be collected at indicated time points for pharmacokinetic analysis.	Up to Day 85
Primary	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
Primary	Part 1: Tmax of cys-mcMMAF	Blood samples will be collected at indicated time points for pharmacokinetic analysis.	Up to Day 85
Primary	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)
Primary	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
Primary	Part 1: Tlast of cys-mcMMAF	Blood samples will be collected at indicated time points for pharmacokinetic analysis.	Up to Day 85
Primary	Part 2: Cmax of GSK2857916	Blood samples will be collected at indicated time points for pharmacokinetic analysis.	Up to Day 85
Primary	Part 2: Tmax of GSK2857916	Blood samples will be collected at indicated time points for pharmacokinetic analysis.	Up to Day 85
Primary	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)
Primary	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)
Primary	Part 2: AUC(0-tau) of GSK2857916	Blood samples will be collected at indicated time points for pharmacokinetic analysis.	Up to Day 85
Primary	Part 2: Tlast of GSK2857916	Blood samples will be collected at indicated time points for pharmacokinetic analysis.	Up to Day 85
Primary	Part 2: Cmax of total mAb	Blood samples will be collected at indicated time points for pharmacokinetic analysis.	Up to Day 85
Primary	Part 2: Tmax of total mAb	Blood samples will be collected at indicated time points for pharmacokinetic analysis.	Up to Day 85
Primary	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)
Primary	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)
Primary	Part 2: AUC(0-tau) of total mAb	Blood samples will be collected at indicated time points for pharmacokinetic analysis.	Up to Day 85
Primary	Part 2: Tlast of total mAb	Blood samples will be collected at indicated time points for pharmacokinetic analysis.	Up to Day 85
Primary	Part 2: Cmax of cys-mcMMAF	Blood samples will be collected at indicated time points for pharmacokinetic analysis.	Up to Day 85
Primary	Part 2: Tmax of cys-mcMMAF	Blood samples will be collected at indicated time points for pharmacokinetic analysis.	Up to Day 85
Primary	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)
Primary	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
Primary	Part 2: Tlast of cys-mcMMAF	Blood samples will be collected at indicated time points for pharmacokinetic analysis.	Up to Day 85
Secondary	Part 1 and Part 2: Change from Baseline in Vital Signs- Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) (millimeter of mercury [mmHg])	Vital signs will be measured after resting for at least 5 minutes.	Baseline and up to 48 months
Secondary	Part 1 and Part 2: Change from Baseline in Vital Sign- Heart rate (beats per minute)	Vital signs will be measured after resting for at least 5 minutes.	Baseline and up to 48 months
Secondary	Part 1 and Part 2: Number of participants with adverse events (AEs) and serious adverse events (SAEs)	AEs and SAEs will be collected at specified time points.	Up to 48 months
Secondary	Part 1 and Part 2: Number of participants with toxicity grading for clinical laboratory parameters		Up to 48 months
Secondary	Part 1 and Part 2: Change from baseline in physical examination parameter	Physical examination parameter will include assessment of weight only.	Baseline and up to 48 months