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NCT07227311PHASE2Recruiting

A Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin in Combination With Standard of Care in Participants With Relapsed-Refractory Multiple Myeloma (RRMM)

GlaxoSmithKline

Start Date

4/15/2026

Completion Date

8/30/2030

Summary

This study is for adults with multiple myeloma (a type of blood cancer) that has come back after being treated earlier or isn't responding to the current treatment. The main goal is to find out if the study drug, belantamab mafodotin, given less often (on an extended schedule) with other cancer medicines, can still treat the cancer effectively while causing fewer side effects, especially those affecting the eyes. The study will also look at how well the treatment works overall and how safe it is when administered to the participants.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: • Participants are eligible to be included in the study only if all of the following criteria apply: Applicable to All Arms - BPd, BVd, BKd: * Male or female, 18 years or older (at the time consent is obtained). * Have a confirmed diagnosis of Multiple Myeloma (MM) as defined by the International Myeloma Working Group (IMWG) criteria. * Eastern Cooperative Oncology Group (ECOG) performance status of zero to 2. * Have been previously treated with at least 1, but no more than 2, prior lines of MM therapy and must have documented disease progression during or after their most recent therapy. * Must have at least 1 aspect of measurable disease, defined as one the following: 1. Urine M-protein excretion ≥200 mg/24 h, or 2. Serum M-protein concentration ≥0.5 g/dL (≥5.0 g/L), or 3. Free Light Chain (FLC) assay: involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum free light chain ratio (\<0.26 or \>1.65) only if patient has no measurable urine or serum M spike. * Patients with a history of Autologous Stem Cell Transplant (ASCT) are eligible for study participation provided the following eligibility criteria are met: 1. ASCT was \>100 days prior to the first dose of study medication, 2. No active bacterial, viral, or fungal infection(s) present. * All prior treatment-related toxicities (defined by National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] v5.0) must be ≤Grade 1 at the time of enrollment, except for alopecia. * Adequate organ system functions as defined by the laboratory assessments. * Contraceptive requirements for men and women per local regulations; strict pregnancy prevention for women of childbearing potential (WOCBP), including negative pregnancy tests and use of highly effective contraception. * Male participants must refrain from sperm donation and must use a condom plus an additional highly effective method of contraception if sexually active with a woman of childbearing potential. Specific Inclusion Criteria for BPd arm: • Prior treatment must include a lenalidomide-containing regimen, with lenalidomide administered for at least 2 consecutive cycles. Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: Applicable for all (BPd, BVd, BKd): * Active plasma cell leukemia at Screening. * Symptomatic amyloidosis, including active Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma proliferative disorder, and Skin changes (POEMS). * Previous or concurrent invasive malignancy other than MM, except: 1. The disease must be considered medically stable for at least 2 years; or 2. The patient must not be receiving active therapy, other than hormonal therapy for this disease. * Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to belantamab mafodotin or drugs chemically related to belantamab mafodotin, or any of the components of the study treatment. * Plasmapheresis within 7 days prior to the first dose of study intervention. * Patients after prior allogeneic stem cell transplant * Any major surgery within 4 weeks prior to start of treatment, except for bone stabilizing surgery. * Evidence of active mucosal or internal bleeding. * Intolerance or contraindications to anti-viral prophylaxis. * Current corneal epithelial disease except for mild punctate keratopathy. * Systemic anti-myeloma therapy (including chemotherapy and systemic steroids); prior treatment with an anti-MM monoclonal antibody drug within 30 days of receiving the first dose of study intervention. * Presence of active renal condition (infection, requirement for dialysis, or any other condition that could affect participant's safety). Patients with isolated proteinuria resulting from MM are eligible, provided they fulfill certain criteria * Received prior B-cell maturation antigen (BCMA)-targeted therapy. * Contact lenses are prohibited while receiving belantamab mafodotin treatment. Use may be restarted after a qualified eye care specialist confirms there are no other contraindications. Bandage contact lenses are permitted during study treatment as directed by the treating eye care specialist. * HIV infection unless well-controlled, no recent AIDS-defining infections, and adequate CD4+ count. * Significant liver dysfunction (ALT \>2.5x ULN, bilirubin \>1.5x ULN, cirrhosis, unstable liver/biliary disease). * Positive hepatitis B or C markers unless criteria for resolved infection are met. * Evidence of cardiovascular risk including any of the following: untreated arrhythmias, recent MI/ACS/angioplasty/bypass, NYHA III/IV heart failure, uncontrolled hypertension, QTc prolongation. Specific Exclusion Criteria for BPd Arm: * Received prior treatment with or intolerant to pomalidomide. * Active or history of venous and arterial thromboembolism within the past 3 months. Specific Exclusion Criteria for BVd Arm: * Intolerant to bortezomib or refractory to bortezomib (defined as progressive disease during treatment with a bortezomib-containing regimen of 1.3 mg/m² twice weekly or within 60 days of completing that treatment). * Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain. Specific Exclusion Criteria for BKd Arm: * Intolerant to carfilzomib or refractory to carfilzomib (defined as progressive disease during treatment with a carfilzomib-containing regimen or within 60 days of completing that treatment). * Known history of allergy to captisol (i.e., cyclodextrin derivatives) used to solubilize carfilzomib. * Left ventricular ejection fraction \<40% as assessed by transthoracic echocardiogram. * Pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to enrolment. * Intolerance to hydration due to pre-existing pulmonary or cardiac impairment. * Known pulmonary hypertension.

Interventions

DRUG

Belantamab mafodotin

DRUG

Dexamethasone

DRUG

Pomalidomide

DRUG

Bortezomib

DRUG

Carfilzomib

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Conditions

Multiple Myeloma

Locations

GSK Investigational Site

Los Alamitos, California 90720

United States

GSK Investigational Site

Torrance, California 90505

United States

GSK Investigational Site

Whittier, California 90602

United States

GSK Investigational Site

Fort Myers, Florida 33912

United States

GSK Investigational Site

Macon, Georgia 31210

United States

GSK Investigational Site

Baton Rouge, Louisiana 70809

United States

GSK Investigational Site

Bethesda, Maryland 20817

United States

GSK Investigational Site

Bridgeton, Missouri 63044

United States

GSK Investigational Site

Springfield, Missouri 65807

United States

GSK Investigational Site

Farmington, New Mexico 87401

United States

GSK Investigational Site

Nashville, Tennessee 37203

United States

GSK Investigational Site

Dunkirk, Nord 59240

France

GSK Investigational Site

Nantes, 44093

France

GSK Investigational Site

Paris, 75012

France

GSK Investigational Site

Paris, 75475

France

GSK Investigational Site

Paris, 75651

France

GSK Investigational Site

Saint-Etienne,

France

GSK Investigational Site

Frankfurt, 60389

Germany

GSK Investigational Site

Hamburg, 22763

Germany

GSK Investigational Site

Karlsruhe, 76133

Germany

GSK Investigational Site

Koblenz, 56068

Germany

GSK Investigational Site

München, 80634

Germany

GSK Investigational Site

Athens, 106 76

Greece

GSK Investigational Site

Athens, 11528

Greece

GSK Investigational Site

Thessaloniki, 57010

Greece

GSK Investigational Site

Aichi, 467-8602

Japan

GSK Investigational Site

Chiba, 277-8567

Japan

GSK Investigational Site

Ehime, 790-8524

Japan

GSK Investigational Site

Fukushima, 960-1295

Japan

GSK Investigational Site

Gunma, 371-8511

Japan

GSK Investigational Site

Hokkaido, 060-8543

Japan

GSK Investigational Site

Ishikawa, 920-8641

Japan

GSK Investigational Site

Numakunai, 028-3695

Japan

GSK Investigational Site

Okayama, 701-1192

Japan

GSK Investigational Site

Osaka, 590-0197

Japan

GSK Investigational Site

Sendai, 983-8520

Japan

GSK Investigational Site

Tokyo, 105-8471

Japan

GSK Investigational Site

Yamanashi, 409-3898

Japan

GSK Investigational Site

Amersfoort, 3813 TZ

Netherlands

GSK Investigational Site

Hoofddorp, 2130 AT

Netherlands

GSK Investigational Site

The Hague, 2545 AA

Netherlands

GSK Investigational Site

Ulsan, 44033

South Korea

GSK Investigational Site

Jerez de la Frontera, Andalusia 11407

Spain

GSK Investigational Site

Badalona, 08916

Spain

GSK Investigational Site

Córdoba, 14004

Spain

GSK Investigational Site

Gijón, 33394

Spain

GSK Investigational Site

Madrid, 28006

Spain

GSK Investigational Site

Madrid, 28041

Spain

GSK Investigational Site

Málaga, 29010

Spain

GSK Investigational Site

Salamanca, 37007

Spain

GSK Investigational Site

Vitoria-Gasteiz, 01009

Spain