A Study to Investigate the Safety and Efficacy of Belantamab for the Treatment of Multiple Myeloma When Used as Monotherapy and in Combination Treatments

NCT05714839 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2186702022-501941-63
• Study Type: interventional
• Target: 153
• Locations: 10 countries
• Sites: 27

Brief Summary

The study consists of three parts:

• Part 1 The primary purpose of this part aims to evaluate the safety, tolerability, and clinical activity of escalating doses of single agent Unconjugated belantamab antibody in participants with refractory multiple myeloma (RRMM) who have received at least 3 prior therapies (4L+).
• Part 2 The primary purpose of this part is to evaluate the safety, tolerability, and clinical activity of different dose ratios of belantamab mafodotin in combination with Unconjugated belantamab antibody (delivered as separate drugs) in participants with RRMM who have received at least 3 prior therapies (4L+).
• Part 3: The Primary purpose of this part will evaluate the clinical activity of a selected dose of the unconjugated belantamab antibody, either alone or in combination with belantamab mafodotin alongside the standard of care (SoC) pomalidomide-dexamethasone backbone. The study will focus on patients with multiple myeloma who have undergone at least one prior line of therapy, including treatment with lenalidomide.

Conditions

Multiple Myeloma

Keywords

Unconjugated belantamab antibody Belantamab Mafodotin; Relapsed or Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (6)

• Part 1, 2 and 3: Number of Participants with any Adverse Event

  Up to 52 months

• Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)

  Cycle 1 (Each cycle is of 28 days)

• Part 1, 2and 3: Number of Participants with Worst Case Grade Change from Baseline in Laboratory and Vital Sign Parameters

  Up to 52 months

• Part 1, 2 and 3: Number of Participants with severity of ocular events by the Keratopathy Visual Acuity (KVA) scale

  Up to 52 months

• Part 2: Overall Response Rate (ORR)

  Up to 52 months

• Part 3: Very Good Partial Response and better rate (VGPR+)

  VGPR+ is defined as the percentage of participants with a confirmed VGPR or better (i.e., VGPR, complete response, stringent complete response)

  Up to 52 months

Secondary Outcomes (31)

• Part 1: Observed Plasma Concentration of belantamab

  Up to 52 months

• Part 1: Area Under the Curve (AUC) of belantamab

  Up to 52 months

• Part 1: Maximum Concentration (Cmax) of belantamab

  Up to 52 months

• Part 1: Number of Participants with Anti-Drug Antibodies (ADA) against belantamab

  Up to 52 months

• Part 1: Titers of ADA against belantamab

  Up to 52 months

Study Arms (4)

Part 1: Dose escalation and expansion of the unconjugated belantamab antibody monotherapy

EXPERIMENTAL

Unconjugated belantamab antibody will be administered in participants with RRMM until progressive disease (PD)

Drug: Unconjugated belantamab antibody

Part 2:Unconjugated belantamab antibody and belantamab mafodotin-given separately dose range finding

EXPERIMENTAL

Participants with RRMM will receive unconjugated belantamab antibody and belantamab mafodotin

Drug: Unconjugated belantamab antibody and belantamab mafodotin

Part 3: Unconjugated belantamab +/- belantamab mafodotin +pomalidomide/dexamethasone in 2L+ RRMM

EXPERIMENTAL

Participants with second line (2L+) RRMM will receive Unconjugated belantamab antibody in combination with pomalidomide-dexamethasone backbone, with or without belantamab mafodotin.

Drug: Unconjugated belantamab antibody in combination with pomalidomide-dexamethasone backbone, with or without belantamab mafodotin

Part 1b:Optional belantamab mafodotin

EXPERIMENTAL

Participants enrolled in Part 1 and Part 2 will be dosed until PD after which they will have the option to receive treatment with single agent belantamab mafodotin.

Drug: Belantamab mafodotin

Interventions

Belantamab mafodotin DRUG

Belantamab mafodotin will be administered.

Also known as: GSK2857916

Part 1b:Optional belantamab mafodotin

Unconjugated belantamab antibody DRUG

Unconjugated belantamab antibody will be administered.

Also known as: GSK2857914

Part 1: Dose escalation and expansion of the unconjugated belantamab antibody monotherapy

Unconjugated belantamab antibody and belantamab mafodotin DRUG

Unconjugated belantamab antibody and belantamab mafodotin used in combination (delivered as separate drugs) will be administered.

Also known as: GSK2857914 and GSK2857916

Part 2:Unconjugated belantamab antibody and belantamab mafodotin-given separately dose range finding

Unconjugated belantamab antibody in combination with pomalidomide-dexamethasone backbone, with or without belantamab mafodotin DRUG

Unconjugated belantamab antibody and belantamab mafodotin in combination with pomalidomide-dexamethasone and Unconjugated belantamab antibody in combination with pomalidomide-dexamethasone will be administered.

Part 3: Unconjugated belantamab +/- belantamab mafodotin +pomalidomide/dexamethasone in 2L+ RRMM

Eligibility Criteria

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

You may qualify if:

• Participants at the time of signing the Informed Consent Form (ICF) are at least 18 years old or are of the legal age of consent in the jurisdiction in which the study is taking place.
• Participants who have histologically or cytologically confirmed diagnosis of Multiple Myeloma (MM), as defined by the international myeloma working group (IMWG) and have progressed on or following the last line of treatment Part 1 and Part 2: Participants who have received at least 3 prior lines of anti-myeloma treatments, , including lenalidomide, a proteasome inhibitor, and an anti-CD38 mAb either in combination or separately.
• Part 3: Have received at least 1 prior line of treatment anti-myeloma treatments, including lenalidomide. Prior anti-CD38-containing regimen is not mandated, however no more than 70% of participants recruited may be anti-CD38 naïve
• Participants with a history of Autologous stem cell transplant (ASCT) are eligible for study participation provided the following eligibility criteria are met:
• Transplant was greater than (\>)100 days prior to screening.
• No active bacterial, viral, or fungal infection(s) present
• Eastern cooperative oncology group-performance status (ECOG-PS) of 0 to 2.
• Measurable disease defined as at least ONE of the following:
• Serum M-protein concentration greater than (\>=) 0.5 gram (g)/ deciliter (dL) (\>=5 gram/liter \[g/L\])
• Urine M-protein excretion \>=200 milligram(mg)/24 hours (\>=0.2 g/24 hours)
• Serum free light chain (FLC) assay: involved FLC level \>=10 mg/dL (\>=100 milligrams per liter \[mg/L\]) and an abnormal serum FLC ratio (less than \[\<\]0.26 or \>1.65)
• Have adequate organ system function as defined by the laboratory assessments
• All prior treatment-related toxicities (defined by National Cancer Institute-Common Toxicity Criteria for Adverse Events \[NCI-CTCAE\], v5.0, 2017) must be Grade \<=1 at the time of screening except for alopecia (any grade), neuropathy (Grade \<=2), or endocrinopathy managed with replacement therapy (any grade).
• Participants or legally authorized representative (LAR) capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
• Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

You may not qualify if:

• Diagnosis of primary Amyloid Light chain (AL) Amyloidosis, active Polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes (POEMS) syndrome, primary plasma cell leukemia.
• Part 3: Active or history of venous or arterial thromboembolism within the past 3 months. Contraindications to or unwilling to undergo protocol-required anti-thrombotic prophylaxis
• 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.
• Participant is exhibiting signs of meningeal or central nervous system involvement with MM.
• Current corneal epithelial disease except nonconfluent Superficial punctate keratitis (SPK).
• 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.
• Presence of malignancies other than disease under study are excluded, except for any other malignancy from which the participant has been disease-free for more than 2 years and, in the opinion of the Principal investigator (PI) and GlaxoSmithKline (GSK) Medical Director, will not affect the evaluation of the effects of this clinical trial treatment on the currently targeted malignancy (MM).Participants on active surveillance or hormone treatment for non-metastatic prostate cancer are not excluded. Participants on hormone therapy for non-metastatic breast cancer are not excluded
• 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.
• Part 1 dose escalation and Part 2 only: QT interval corrected using Fridericia's formula (QTcF) interval \>480 millisecond(msec) (QT interval corrected for heart rate according to Fridericia's formula), and/or hypokalemia, and/or family history of long QT syndrome.
• Part 1 dose expansion and Part 3: Not applicable.
• History of 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
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to Unconjugated belantamab antibody / belantamab mafodotin or any of the components of the study treatment. History of severe hypersensitivity to other Monoclonal antibodies (mAbs).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (27)

GSK Investigational Site

Grand Rapids, Michigan, 49546, United States

RECRUITING

GSK Investigational Site

Chapel Hill, North Carolina, 27514, United States

RECRUITING

GSK Investigational Site

Chattanooga, Tennessee, 37404, United States

RECRUITING

GSK Investigational Site

Nashville, Tennessee, 37203, United States

RECRUITING

GSK Investigational Site

Ciudadela, B1702, Argentina

COMPLETED

GSK Investigational Site

San Juan Bautista, B1888AAE, Argentina

RECRUITING

GSK Investigational Site

Viedma, R8500ACE, Argentina

RECRUITING

GSK Investigational Site

Fitzroy, Victoria, 3065, Australia

RECRUITING

GSK Investigational Site

Nedlands, Western Australia, 6009, Australia

COMPLETED

GSK Investigational Site

Joinville, 89201-260, Brazil

RECRUITING

GSK Investigational Site

Salvador, 41253-190, Brazil

RECRUITING

GSK Investigational Site

São Paulo, 04537-080, Brazil

RECRUITING

GSK Investigational Site

Aomori, 030-8553, Japan

RECRUITING

GSK Investigational Site

Chiba, 277-8577, Japan

RECRUITING

GSK Investigational Site

Osaka, 545-8586, Japan

COMPLETED

GSK Investigational Site

Tokyo, 105-8471, Japan

RECRUITING

GSK Investigational Site

Gdansk, 80-214, Poland

WITHDRAWN

GSK Investigational Site

Lublin, 20-081, Poland

RECRUITING

GSK Investigational Site

Seoul, 137-701, South Korea

RECRUITING

GSK Investigational Site

Seoul, 138-736, South Korea

RECRUITING

GSK Investigational Site

Changhua, 500, Taiwan

RECRUITING

GSK Investigational Site

Taipei, 100, Taiwan

RECRUITING

GSK Investigational Site

Istanbul, 34010, Turkey (Türkiye)

RECRUITING

GSK Investigational Site

Kayseri, 38039, Turkey (Türkiye)

RECRUITING

GSK Investigational Site

Leicester, LE1 5WW, United Kingdom

RECRUITING

GSK Investigational Site

Oxford, OX3 7LE, United Kingdom

COMPLETED

GSK Investigational Site

Plymouth, PL6 8DH, United Kingdom

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

belantamab mafodotin

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

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 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2023
• First Posted: February 6, 2023
• Study Start: June 14, 2023
• Primary Completion (Estimated): December 3, 2029
• Study Completion (Estimated): December 3, 2029
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Locations

JP (4); PL (2); KR (2); AR (3); US (4); BR (3); AU (2); TW (2); TU (2); GB (3)