A Study to Evaluate the Subcutaneous Belantamab (BCMAb) Formulation Versus Intravenous Belantamab in Participants With Multiple Myeloma While Treated With Standard of Care

Official title

A Randomized, Open-label, Phase 1b, Crossover Study to Evaluate the Pharmacokinetics and Safety of a Subcutaneous Belantamab (BCMAb) Formulation With rHuPH20 Versus Intravenous Belantamab in Participants With Multiple Myeloma While Treated With Standard of Care

Overview

This study aims to compare how belantamab behaves in the body when given as an injection under the skin (SC) versus into a vein (IV) in participants with multiple myeloma who are receiving standard of care treatment, to enable eventual development of SC formulation. It will assess how much belantamab is absorbed and how long it stays in the blood as well as assess whether it is safe and tolerated well by participants.

Interventions

• Drug Belantamab SC
  Belantamab will be administered via SC route.
• Drug Belantamab IV
  Belantamab will be administered via IV route.
• Drug Recombinant Human Hyaluronidase PH20 (rHuPH20)
  rHuPH20 will be administered via SC route.
• Drug Standard of care
  Participants will receive standard of care: Lenalidomide and/or anti-CD38 mAb as maintenance therapy.

Primary outcome measures

• Bioavailability of belantamab [Time frame: Up to approximately 42 weeks]
• Maximum observed plasma concentration (Cmax) of belantamab [Time frame: Up to approximately 42 weeks]
• Area under concentration-time curve (AUC) of belantamab [Time frame: Up to approximately 42 weeks]
• Plasma concentration of belantamab [Time frame: Up to approximately 42 weeks]
• Number of Participants with Adverse Events (AE) [Time frame: Up to approximately 42 weeks]
• Number of participants with changes in laboratory parameters [Time frame: Up to approximately 42 weeks]
• Number of participants with changes in vital signs [Time frame: Up to approximately 42 weeks]

Secondary outcome measures (2)

• Number of participants with Anti-drug antibodies (ADA) against belantamab [Time frame: Up to approximately 71 weeks]
• Titers of ADA against belantamab [Time frame: Up to approximately 71 weeks]

Eligibility criteria

Inclusion criteria

Participants are eligible to be included in the study only if all of the following criteria apply:

• Participants at the time of signing the Informed Consent Form (ICF) must be aged 18 years old or greater or are of the legal age of consent in the jurisdiction in which the study is taking place.
• Histologically or cytologically confirmed diagnosis of multiple myeloma (MM), as defined by the International Myeloma Working Group (IMWG).
• Currently receiving maintenance therapy with either anti- cluster of differentiation 38 (anti-CD38) directed therapy, or lenalidomide, or both, following autologous stem cell transplantation (ASCT) in either first or second line.
• No change in current myeloma treatment for at least 2 months prior to during screening, or during the trial.
• Partial response (PR) or better per IMWG per Investigator's assessment for at least 2 months prior to screening.
• All current treatment-related toxicities (defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version (v) 6.0, 2025) must be Grade less than or equal to (<=) 2 at the time of screening except for alopecia (any grade), or endocrinopathy managed with replacement therapy (any grade).
• ASCT must be greater than (>) 100 days prior to screening, and participants are transfusion independent and not receiving granulocyte colony-stimulating factor (G-CSF) or thrombopoietin analogies.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Have organ system functions as defined by the laboratory assessments.

Exclusion criteria

Participants are excluded from the study if any of the following criteria apply:

• Diagnosis of primary Amyloid Light chain (AL) Amyloidosis, active polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes (POEMS) syndrome, primary plasma cell leukemia, or non-secretory myeloma.
• 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 with study procedures.
• Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice.
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to belantamab, or hyaluronidase, or any of the components of the study treatment. History of severe hypersensitivity to other monoclonal antibodies (mAbs).
• Active infection requiring antibiotic, antiviral, or antifungal treatment.
• Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant's safety).
• Prior B cell maturation antigen (BCMA) directed therapy.
• Plasmapheresis within 7 days prior to the first dose of study drug.
• Any major surgery (other than bone-stabilizing surgery) within 2 weeks of first dose or has not recovered fully from surgery.
• Participants must not receive live/live attenuated vaccines within 30 days prior to first dose of study treatment or whilst receiving belantamab for at least 70 days following last study treatment.
• Is currently enrolled or has participated in any other clinical study involving an investigational study intervention or any other type within 60 days of an investigational medicinal product before randomization.
• Known human immunodeficiency virus (HIV) infection, unless the participant can meet all the following criteria:

• Established antiretroviral therapy (ART) for at least 4 weeks and HIV viral load <400 copies/milliliter (mL)
• CD4+ T-cell (CD4+) counts greater than or equal to (>=) 350 cells/microliter (uL)
• No history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within the last 12 months
• Participants with hepatitis B virus (HBV) infection will be excluded
• 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 unless the participant can meet the following criteria:

• RNA test negative
• Successful antiviral treatment (usually 8 weeks duration) is required, followed by a negative hepatitis C virus (HCV) RNA test after a washout period of at least 4 weeks.
• Is pregnant or breastfeeding.
• Evidence of cardiovascular risk including any of the following:

• Evidence of current clinically significant untreated arrhythmias, including, but not limited to, clinically significant electrocardiogram (ECG) abnormalities such as 2nd degree (Mobitz Type II) or 3rd degree atrioventricular (AV) block.
• History of myocardial infarction (MI), acute coronary syndromes (including unstable angina), coronary angioplasty, stenting or bypass grafting, all within three months of screening.
• Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
• Uncontrolled hypertension.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07742527 · 309296

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗