To Evaluate Safety, Tolerability, and Clinical Activity of the Antibody-drug Conjugate, GSK2857916 Administered in Combination With Lenalidomide Plus Dexamethasone (Arm A), or in Combination With Bortezomib Plus Dexamethasone (Arm B) in Participants With Relapsed/Refractory Multiple Myeloma (RRMM)

NCT ID: NCT03544281

Last Updated: 2025-03-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 153 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-20
• Study Completion Date: 2024-02-28

Brief Summary

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Belantamab mafodotin

Intervention Type: DRUG

Selected doses of belantamab mafodotin will be administered as an infusion.

Lenalidomide

Intervention Type: DRUG

Lenalidomide will be administered as 25 or 10 mg,orally, with belantamab mafodotin and dexamethasone.

Dexamethasone

Intervention Type: DRUG

Dexamethasone will be administered as 20 or 40 mg, orally with belantamab mafodotin.

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.

Group Type: EXPERIMENTAL

Belantamab mafodotin

Intervention Type: DRUG

Selected doses of belantamab mafodotin will be administered as an infusion.

Dexamethasone

Intervention Type: DRUG

Dexamethasone will be administered as 20 or 40 mg, orally with belantamab mafodotin.

Bortezomib

Intervention Type: DRUG

Bortezomib will be administered as 1.3 mg/m\^2, as SC or IV, with belantamab mafodotin and dexamethasone.

Interventions

Belantamab mafodotin

Selected doses of belantamab mafodotin will be administered as an infusion.

Intervention Type: DRUG

Lenalidomide

Lenalidomide will be administered as 25 or 10 mg,orally, with belantamab mafodotin and dexamethasone.

Intervention Type: DRUG

Dexamethasone

Dexamethasone will be administered as 20 or 40 mg, orally with belantamab mafodotin.

Intervention Type: DRUG

Bortezomib

Bortezomib will be administered as 1.3 mg/m\^2, as SC or IV, with belantamab mafodotin and dexamethasone.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Iqvia Pty Ltd

INDUSTRY

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Birmingham, Alabama, United States

GSK Investigational Site

Goodyear, Arizona, United States

GSK Investigational Site

Atlanta, Georgia, United States

GSK Investigational Site

Indianapolis, Indiana, United States

GSK Investigational Site

Lansing, Michigan, United States

GSK Investigational Site

St Louis, Missouri, United States

GSK Investigational Site

Grand Island, Nebraska, United States

GSK Investigational Site

Hackensack, New Jersey, United States

GSK Investigational Site

New York, New York, United States

GSK Investigational Site

The Bronx, New York, United States

GSK Investigational Site

Greer, South Carolina, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

Wollongong, New South Wales, Australia

GSK Investigational Site

Woodville, South Australia, Australia

GSK Investigational Site

Fitzroy, Victoria, Australia

GSK Investigational Site

Melbourne, Victoria, Australia

GSK Investigational Site

Melbourne, Victoria, Australia

GSK Investigational Site

Murdoch, Western Australia, Australia

GSK Investigational Site

Nedlands, Western Australia, Australia

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Salamanca, , Spain

GSK Investigational Site

Truro, Cornwall, United Kingdom

GSK Investigational Site

London, , United Kingdom

Countries

United States; Australia; Canada; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-004689-93

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

207497

Identifier Type: -

Identifier Source: org_study_id