A Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin in Combination With Cyclophosphamide, Bortezomib, and Dexamethasone in Adult Participants With Newly Diagnosed Amyloid Light Chain (AL) Amyloidosis

NCT07224672 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2239632025-522803-60
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

The study aims to evaluate the efficacy and safety of belantamab mafodotin in combination with cyclophosphamide, bortezomib, and dexamethasone in adult participants with newly diagnosed (ND) AL amyloidosis .

Conditions

Amyloidosis

Keywords

Amyloid light chain amyloidosis; Bortezomib; Cyclophosphamide; Dexamethasone

Outcome Measures

Primary Outcomes (1)

• Overall complete hematologic response (CHR) rate

  The overall CHR rate is defined as the proportion of participants who achieve a CHR during or after study treatment initiation, as assessed by the investigator, according to the consensus guidelines for AL amyloidosis.

  Up to approximately 24 months

Secondary Outcomes (11)

• Number of participants with non-serious adverse events and serious adverse events

  Up to approximately 24 months

• Number of participants with clinically significant changes in hematology, and chemistry parameters

  Up to approximately 24 months

• Number of participants with ocular findings on ophthalmic examination

  Up to approximately 24 months

• Organ response rate (OrRR)

  Up to approximately 5 years

• Duration of CHR

  Up to approximately 5 years

Study Arms (3)

Dose optimization phase: Belantamab mafodotin dose level 1 + CyBorD

EXPERIMENTAL

Adult participants with newly diagnosed amyloid light chain (AL) amyloidosis will receive Belantamab mafodotin dose level 1 in combination with CyBorD in dose optimization phase.

Drug: Belantamab mafodotin; Drug: Cyclophosphamide; Drug: Bortezomib; Drug: Dexamethasone

Dose optimization phase: Belantamab mafodotin dose level 2+ CyBorD

EXPERIMENTAL

Adult participants with newly diagnosed AL amyloidosis will receive Belantamab mafodotin dose level 2 in combination with CyBorD in dose optimization phase.

Drug: Belantamab mafodotin; Drug: Cyclophosphamide; Drug: Bortezomib; Drug: Dexamethasone

Dose expansion phase: Belantamab mafodotin + CyBorD

EXPERIMENTAL

Adult participants with newly diagnosed AL amyloidosis will receive belantamab mafodotin at selected dose level from dose optimization phase in combination with CyBorD in dose expansion phase.

Drug: Belantamab mafodotin; Drug: Cyclophosphamide; Drug: Bortezomib; Drug: Dexamethasone

Interventions

Bortezomib DRUG

Bortezomib will be administered

Dose expansion phase: Belantamab mafodotin + CyBorD; Dose optimization phase: Belantamab mafodotin dose level 1 + CyBorD; Dose optimization phase: Belantamab mafodotin dose level 2+ CyBorD

Dexamethasone DRUG

Dexamethasone will be administered

Dose expansion phase: Belantamab mafodotin + CyBorD; Dose optimization phase: Belantamab mafodotin dose level 1 + CyBorD; Dose optimization phase: Belantamab mafodotin dose level 2+ CyBorD

Belantamab mafodotin DRUG

Belantamab mafodotin will be administered

Dose expansion phase: Belantamab mafodotin + CyBorD; Dose optimization phase: Belantamab mafodotin dose level 1 + CyBorD; Dose optimization phase: Belantamab mafodotin dose level 2+ CyBorD

Cyclophosphamide DRUG

Cyclophosphamide will be administered

Dose expansion phase: Belantamab mafodotin + CyBorD; Dose optimization phase: Belantamab mafodotin dose level 1 + CyBorD; Dose optimization phase: Belantamab mafodotin dose level 2+ CyBorD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is at least 18 years of age or the legal age of consent
• Has histologically confirmed newly diagnosed primary AL amyloidosis according to the following criteria:
• Presence of an amyloid-related systemic syndrome as per consensus guidelines.
• Positive amyloid staining by Congo red stain with green birefringence on polarized light microscopy in any tissue AND at least 1 of the following tests to confirm amyloid type as AL Characteristic appearance by electron microscopy or confirmatory immunohistochemistry or AL amyloidosis typing by mass spectrometric proteomic analysis of the amyloid deposits or amyloid-typing by immunofluorescence oEvidence of a monoclonal plasma cell proliferative disorder
• Measurable clonal disease as defined by at least 1 of the following:
• Serum monoclonal protein \>=0.5 grams per deciliter (g/dL) by protein electrophoresis (routine serum protein electrophoresis and immunofixation performed at central laboratory),
• Involved serum FLC \>=5.0 milligram per deciliter (mg/dL) with an abnormal kappa:lambda ratio or the difference between involved and uninvolved light chain, FLC concentrations (dFLC) \>=5 mg/dL.
• Not considered candidate for high-dose chemotherapy with autologous stem cell transplantation (ASCT) as part of first line of therapy
• Is willing to use adequate contraception.
• Is capable of giving signed informed consent
• Has an Eastern Cooperative Oncology Group performance status of 0, 1 or 2
• Has adequate hematologic, hepatic and renal function

You may not qualify if:

• Has a previous or current diagnosis of plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes (POEMS) syndrome or symptomatic multiple myeloma (MM), as per International Myeloma Working Group criteria for MM including the presence of lytic bone disease , plasmacytomas, or clonal BM plasma cells \>=60%.
• Has Immunoglobulin M (IgM)-related AL amyloidosis.
• Has any form of non-AL amyloidosis, including wild type or mutated (Transthyretin amyloidosis \[ATTR\]) amyloidosis.
• Has evidence of significant cardiovascular (CV) conditions as specified below:
• New York Heart Association (NYHA) classification IIIb or IV heart failure.
• Heart failure that in the opinion of the investigator is caused by ischemic heart disease (e.g., prior myocardial infarction with documented history of cardiac enzyme elevation and electrocardiogram \[ECG\] changes) or uncorrected valvular disease and not primarily due to AL amyloidosis cardiomyopathy.
• In-participant admission to a hospital for unstable angina or myocardial infarction within the last 3 months prior to screening or percutaneous cardiac intervention with recent stent within last 3 months prior to screening or coronary artery bypass grafting within the last 3 months prior to screening
• Participants with current evidence of clinically significant untreated arrhythmia(s), including clinically significant ECG abnormalities including second-degree (Mobitz Type II) or third-degree atrioventricular block.
• Participants with a history of sustained ventricular tachycardia or aborted ventricular fibrillation or with a history of atrioventricular nodal or sinoatrial nodal dysfunction for which a pacemaker/implantable cardioverter-defibrillator is indicated but not placed (participants who do have a pacemaker/implantable cardioverter-defibrillator are allowed on the study).
• Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) \>450 millisecond (msec) or \>480 msec for participants with bundle branch block. Participants who have a pacemaker may be included regardless of calculated QTc interval.
• Supine systolic blood pressure \<90 millimeters of mercury (mmHg), or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of \>20 mmHg despite medical management (e.g., midodrine, fludrocortisones) in the absence of volume depletion.
• Uncontrolled hypertension.
• Has Mayo stage 3B disease
• Has a current corneal epithelial disease except for mild punctate keratopathy.
• Has previous or concurrent malignancies other than AL amyloidosis, except for any other malignancy that has been considered medically stable for at least 2 yearsThe participant must not be receiving active therapy, other than hormonal therapy for this disease.

Sponsors & Collaborators

• GlaxoSmithKline: lead

MeSH Terms

Conditions

Amyloidosis; Immunoglobulin Light-chain Amyloidosis

Interventions

belantamab mafodotin; Cyclophosphamide; Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Central Study Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718; GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: October 31, 2025
• First Posted: November 5, 2025
• Study Start: March 20, 2026
• Primary Completion (Estimated): December 13, 2032
• Study Completion (Estimated): December 13, 2032
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share