Study to Investigate Alternative Dosing Regimens of Belantamab Mafodotin in Participants With Relapsed or Refractory Multiple Myeloma (DREAMM 14)

GlaxoSmithKline (GSK)

Status and phase: Active, not recruiting; Phase 2

Conditions: Multiple Myeloma

Treatments: Drug: Belantamab mafodotin

Study type: Interventional

Funder types: Industry

Identifiers

NCT05064358

2021-004151-16 (EudraCT Number)

209628

Details and patient eligibility

About

This study aims to evaluate alternative dosing regimens of single-agent belantamab mafodotin in participants with relapsed or refractory multiple myeloma (RRMM) to determine if an improved overall benefit/risk profile can be achieved by modifying the belantamab mafodotin dose, schedule, or both.

Enrollment: 177 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participant must be 18 years of age inclusive at the time of signing the informed consent form (ICF).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Histologically or cytologically confirmed diagnosis of MM and a. Has undergone stem cell transplant or is considered transplant ineligible, and b. Has failed at least 3 prior lines of anti-myeloma therapies, including an anti-cluster of differentiation (CD)38 antibody (e.g., daratumumab) alone or in combination and is refractory to an immunomodulatory agent (e.g., lenalidomide, pomalidomide) and a proteasome inhibitor (e.g., bortezomib, ixazomib, carfilzomib).
• France specific: participants have failed at least 4 prior lines of anti-myeloma therapies
• Participant has measurable disease per modified IMWG criteria.
• Life expectancy of at least 6 months, in the opinion of the investigator.
• Male and female participants agree to abide by protocol-defined contraceptive requirements.
• Participant is capable of giving signed informed consent.
• Participant meets country-specific inclusion criteria described in the protocol.

Exclusion criteria

• Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes), or active plasma cell leukemia at the time of screening.
• Current corneal epithelial disease, except nonconfluent superficial punctate keratitis (SPK).
• Evidence of active mucosal or internal bleeding.
• Presence of an active renal condition.
• Any serious and/or unstable pre-existing medical condition, psychiatric disorder, or other conditions that could interfere with the participant's safety, obtaining informed consent, or compliance with the study procedures.
• Malignancies other than the disease under study, except for any other malignancy from which the participant has been disease free for >2 years and, will not affect the evaluation of the effects of the study treatment on the currently targeted malignancy (MM). Participants with curatively treated non-melanoma skin cancer may be enrolled without a 2-year restriction.
• Evidence of cardiovascular risk as per the protocol criteria.
• Pregnant or lactating female.
• Active infection requiring antibiotic, antiviral, or antifungal treatment.
• Known human immunodeficiency virus (HIV) infection, unless the criteria in protocol can be met.
• Hepatitis B and C will be excluded unless the criteria in protocol can be met.
• Cirrhosis or current unstable liver or biliary disease.
• Alanine aminotransferase (ALT) >2.5× upper limit of normal (ULN).
• Total Bilirubin >1.5×ULN.
• Systemic anti-MM therapy within <=14 days or 5 half-lives, whichever is shorter.
• Systemic therapy with high dose steroids within <=14 days before the first dose of study treatment.
• Prior allogenic stem cell transplant.
• Prior treatment with a monoclonal antibody <=30 days before the first dose of study treatment. Use of monoclonal antibodies for serious conditions unrelated to multiple myeloma, such as COVID, may be permitted.
• Prior treatment with an anti-B cell maturation antigen (BCMA) targeted therapy or hypersensitivity reactions to any components of the study treatment.
• Treatment with an antibody-drug conjugate.
• Participant has received any major surgery <=4 weeks before the first dose of study treatment. An exception may be allowed for bone stabilizing surgery.
• Inadequate bone marrow reserve or organ functions as demonstrated by any of the following: a. Absolute neutrophil count <1.0×10^9/L, b. Hemoglobin <8 gram/deciliter (g/dL), c. Platelet count <50×10^9/L, d. Spot urine (albumin/creatinine ratio) >500 milligram/gram (mg/g), e. Estimated glomerular filtration rate (eGFR) <30 milliliter per minute per 1.73 meter square (mL/min/1.73m^2).
• UK specific: a. Absolute neutrophil count <1.5×10^9/L, c. Platelet count <75×10^9/L

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

177 participants in 5 patient groups

Cohort 1: Participants receiving belantamab mafodotin at dose level (DL) 1

Experimental group

Treatment:

Drug: Belantamab mafodotin

Cohort 2: Participants receiving belantamab mafodotin at DL 2

Experimental group

Treatment:

Drug: Belantamab mafodotin

Cohort 3: Participants receiving belantamab mafodotin at DL 3

Experimental group

Treatment:

Drug: Belantamab mafodotin

Cohort 4: Participants receiving belantamab mafodotin at DL 4

Experimental group

Treatment:

Drug: Belantamab mafodotin

Cohort 5: Participants receiving belantamab mafodotin at DL4 with alternative dose modification

Experimental group

Treatment:

Drug: Belantamab mafodotin