Platform Study of Belantamab Mafodotin as Monotherapy and in Combination With Anti-cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM)

NCT ID: NCT04126200

Last Updated: 2025-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

208 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-07

Study Completion Date

2027-03-11

Brief Summary

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B-cell maturation antigen (BCMA) is a target present on tumor cells in participants with multiple myeloma. Belantamab mafodotin (GSK2857916); is an antibody-drug conjugate (ADC) containing humanized anti-BCMA monoclonal antibody (mAb). This is a phase I/II, randomized, open-label, platform study designed to evaluate the effects of belantamab mafodotin in combination with other anti-cancer drugs in participants with relapsed/refractory multiple myeloma. The Platform design incorporates a single master protocol, where multiple treatment combinations, as sub-studies, will be evaluated simultaneously.

Detailed Description

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Conditions

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Multiple Myeloma

Keywords

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Belantamab mafodotin GSK2857916 GSK3174998 Feladilimab Nirogacestat Dostarlimab Isatuximab Lenalidomide Dexamethasone Pomalidomide Platform study Relapsed/Refractory Multiple Myeloma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

There will be a dose exploration (DE) phase which will evaluate the safety and tolerability profile of belantamab mafodotin when administered in combination with other anti-cancer treatments. A recommended Phase 2 dose (RP2D) for each combination treatment will be identified based on the safety and preliminary efficacy in DE. This will be followed by a cohort expansion (CE) phase which will evaluate the clinical activity of the combination treatment in comparison to belantamab mafodotin monotherapy in additional participants.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Belantamab mafodotin+GSK3174998 dose exploration (Sub-study 1)

Group Type EXPERIMENTAL

Belantamab mafodotin

Intervention Type DRUG

Belantamab mafodotin will be administered.

GSK3174998

Intervention Type DRUG

GSK3174998 will be administered.

Belantamab mafodotin+feladilimab dose exploration (Sub-study 2)

Group Type EXPERIMENTAL

Belantamab mafodotin

Intervention Type DRUG

Belantamab mafodotin will be administered.

Feladilimab

Intervention Type DRUG

feladilimab will be administered.

Belantamab mafodotin+nirogacestat dose exploration(Sub-study 3)

Group Type EXPERIMENTAL

Belantamab mafodotin

Intervention Type DRUG

Belantamab mafodotin will be administered.

Nirogacestat

Intervention Type DRUG

Nirogacestat will be administered.

Belantamab mafodotin+dostarlimab dose exploration(Sub-study 4)

Group Type EXPERIMENTAL

Belantamab mafodotin

Intervention Type DRUG

Belantamab mafodotin will be administered.

Dostarlimab

Intervention Type DRUG

Dostarlimab will be administered.

Belantamab mafodotin+isatuximab dose exploration (Sub-study 5)

Group Type EXPERIMENTAL

Belantamab mafodotin

Intervention Type DRUG

Belantamab mafodotin will be administered.

Isatuximab

Intervention Type DRUG

Isatuximab will be administered.

Belantamab mafodotin+ nirogacestat+ lenalidomide+ dexamethasone dose exploration (Sub-study 6)

Group Type EXPERIMENTAL

Belantamab mafodotin

Intervention Type DRUG

Belantamab mafodotin will be administered.

Nirogacestat

Intervention Type DRUG

Nirogacestat will be administered.

Lenalidomide

Intervention Type DRUG

Lenalidomide will be administered.

Dexamethasone

Intervention Type DRUG

Dexamethasone will be administered.

Belantamab mafodotin+ nirogacestat+ pomalidomide + dexamethasone dose exploration (Sub-study 7)

Group Type EXPERIMENTAL

Pomalidomide

Intervention Type DRUG

Pomalidomide will be administered.

Belantamab mafodotin

Intervention Type DRUG

Belantamab mafodotin will be administered.

Nirogacestat

Intervention Type DRUG

Nirogacestat will be administered.

Dexamethasone

Intervention Type DRUG

Dexamethasone will be administered.

Belantamab mafodotin+ nirogacestat+ lenalidomide+ dexamethasone dose exploration (Sub-study 8)

This cohort will enroll Northeast Asian participants.

Group Type EXPERIMENTAL

Belantamab mafodotin

Intervention Type DRUG

Belantamab mafodotin will be administered.

Nirogacestat

Intervention Type DRUG

Nirogacestat will be administered.

Lenalidomide

Intervention Type DRUG

Lenalidomide will be administered.

Dexamethasone

Intervention Type DRUG

Dexamethasone will be administered.

Belantamab mafodotin monotherapy cohort expansion

Group Type ACTIVE_COMPARATOR

Belantamab mafodotin

Intervention Type DRUG

Belantamab mafodotin will be administered.

Belantamab mafodotin+GSK3174998 cohort expansion (Sub-study 1)

Group Type EXPERIMENTAL

Belantamab mafodotin

Intervention Type DRUG

Belantamab mafodotin will be administered.

GSK3174998

Intervention Type DRUG

GSK3174998 will be administered.

Belantamab mafodotin+ feladilimab cohort expansion (Sub-study 2)

Group Type EXPERIMENTAL

Belantamab mafodotin

Intervention Type DRUG

Belantamab mafodotin will be administered.

Feladilimab

Intervention Type DRUG

feladilimab will be administered.

Belantamab mafodotin+ nirogacestat cohort expansion (Sub-study 3)

Group Type EXPERIMENTAL

Belantamab mafodotin

Intervention Type DRUG

Belantamab mafodotin will be administered.

Nirogacestat

Intervention Type DRUG

Nirogacestat will be administered.

Belantamab mafodotin+ dostarlimab cohort expansion (Sub-study 4)

Group Type EXPERIMENTAL

Belantamab mafodotin

Intervention Type DRUG

Belantamab mafodotin will be administered.

Dostarlimab

Intervention Type DRUG

Dostarlimab will be administered.

Belantamab mafodotin+ isatuximab cohort expansion (Sub-study 5)

Group Type EXPERIMENTAL

Belantamab mafodotin

Intervention Type DRUG

Belantamab mafodotin will be administered.

Isatuximab

Intervention Type DRUG

Isatuximab will be administered.

Belantamab mafodotin+ nirogacestat+ lenalidomide+ dexamethasone cohort expansion (Sub-study 6)

Group Type EXPERIMENTAL

Belantamab mafodotin

Intervention Type DRUG

Belantamab mafodotin will be administered.

Nirogacestat

Intervention Type DRUG

Nirogacestat will be administered.

Lenalidomide

Intervention Type DRUG

Lenalidomide will be administered.

Dexamethasone

Intervention Type DRUG

Dexamethasone will be administered.

Belantamab mafodotin+ nirogacestat+ pomalidomide + dexamethasone cohort expansion (Sub-study 7)

Group Type EXPERIMENTAL

Pomalidomide

Intervention Type DRUG

Pomalidomide will be administered.

Belantamab mafodotin

Intervention Type DRUG

Belantamab mafodotin will be administered.

Nirogacestat

Intervention Type DRUG

Nirogacestat will be administered.

Dexamethasone

Intervention Type DRUG

Dexamethasone will be administered.

Belantamab mafodotin+ nirogacestat+ lenalidomide+ dexamethasone cohort expansion (Sub-study 8)

This cohort will enroll Northeast Asian participants.

Group Type EXPERIMENTAL

Belantamab mafodotin

Intervention Type DRUG

Belantamab mafodotin will be administered.

Nirogacestat

Intervention Type DRUG

Nirogacestat will be administered.

Lenalidomide

Intervention Type DRUG

Lenalidomide will be administered.

Dexamethasone

Intervention Type DRUG

Dexamethasone will be administered.

Interventions

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Pomalidomide

Pomalidomide will be administered.

Intervention Type DRUG

Belantamab mafodotin

Belantamab mafodotin will be administered.

Intervention Type DRUG

GSK3174998

GSK3174998 will be administered.

Intervention Type DRUG

Feladilimab

feladilimab will be administered.

Intervention Type DRUG

Nirogacestat

Nirogacestat will be administered.

Intervention Type DRUG

Dostarlimab

Dostarlimab will be administered.

Intervention Type DRUG

Isatuximab

Isatuximab will be administered.

Intervention Type DRUG

Lenalidomide

Lenalidomide will be administered.

Intervention Type DRUG

Dexamethasone

Dexamethasone will be administered.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Participant must be 18 years of age inclusive or older, at the time of signing the informed consent.
* Participants must have histologically or cytologically confirmed diagnosis of Multiple Myeloma (MM), as defined by the IMWG.
* Participants having at least 3 prior lines of prior anti-myeloma treatments including an immunomodulating agent (IMID) a proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody.
* Participants with a history of autologous stem cell transplant are eligible for study participation when, transplant was \>100 days prior to study enrolment and with no active infection(s).
* Participants with Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, unless ECOG less than equal to (\<=)2 is due solely to skeletal complications and/or skeletal pain due to MM.
* Participants with measurable disease defined as at least one of the following: Serum M-protein greater than equal to (\>=)0.5 gram per deciliter (\>=5 gram per liter) or Urine M-protein \>=200 milligrams (mg) per 24 hours or Serum free light chain (FLC) assay: Involved FLC level \>=10 mg per deciliter (\>=100 mg per Liter) and an abnormal serum FLC ratio (\<0.26 or \>1.65).
* Participants who have tested positive for Hepatitis B core antibody (HBcAb) can be enrolled if the following criteria are met: Serology result HBcAb+, Hepatitis B surface antigen (HBsAg)-; HBV deoxyribonucleic acid (DNA) undetectable during screening.
* Participants who are currently receiving physiological doses oral steroids (\<10 mg/day), inhaled steroids or ophthalmalogical steroids.


* Participants with contraception requirements specific to Sub-study 6, 7, and 8 respectively.
* Participants with platelets value for Adequate Organ System Function is ≥75 × 10\^9/L.


\- In Japan, participants should reside in Japan and be Japanese as defined by having all biological Japanese grandparents. Similarly, in China, subjects should reside in China and be Chinese as defined by having all biological Chinese grandparents.

Exclusion Criteria

* Participants with current corneal epithelial disease except mild punctate keratopathy.
* Participants with evidence of cardiovascular risk.
* Participants with known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to belantamab mafodotin or any of the components of the study treatment. History of severe hypersensitivity to other mAb.
* Participants with active infection requiring antibiotic, antiviral, or antifungal treatment.
* Participants with other monoclonal antibodies within 30 days or systemic anti-myeloma therapy within \<14 days.
* Participants with prior radiotherapy within 2 weeks of start of study therapy.
* Participants with prior allogeneic transplant are prohibited.
* Participants who have received prior Chimeric Antigen T cell therapy (CAR-T) therapy with lymphodepletion with chemotherapy within 3 months of screening.
* Participants with any major surgery (other than bone-stabilizing surgery) within the last 30 days.
* Participants with prior treatment with an investigational agent within 14 days or 5 half-lives of receiving the first dose of study drugs, whichever is shorter.
* Participants with \>=grade 3 toxicity considered related to prior check-point inhibitors and that led to treatment discontinuation.
* Participants who have received transfusion of blood products within 2 weeks before the first dose of study drug.
* Participants must not receive live attenuated vaccines within 30 days prior to first dose of study treatment or whilst receiving belantamab mafodotin +- partner agent in any sub-study arm of the platform trial and for at least 70 days following last study treatment.
* Participants with presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant's safety). Participants with isolated proteinuria resulting from MM.
* Participants with known human immunodeficiency virus (HIV) infection, unless the participant can meet all criteria: a) established anti-retroviral therapy for at least 4 weeks and HIV viral load\<400 copies/milliliter (mL) b) cluster of differentiation 4 plus (CD4+) T-cell (CD4+) counts \>= 350 cells/microliter (µL) c) No history of Acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within the last 12 months in which case the participant would be eligible for CE Phase only.

For participants receiving nirogacestat, HIV drugs that are strong Cytochrome P450 3A4 (CYP3A4) inhibitors are prohibited. HIV drugs that are moderate CYP3A4 inhibitors, while permitted, should be co-administered with caution and must be accompanied by nirogacestat dose modifications.


* Participants with autoimmune disease (current or history) or syndrome that required systemic treatment within the past 2 years.
* Exclusion for a recent (within the past 6 months) history of symptomatic pericarditis.


* Participants with uncontrolled small and/or large intestinal disease.
* Participants with uncontrolled skin disease.
* Participants with any condition causing hypophosphatemia, hypokalemia or hypomagnesemia which is refractory to electrolyte replacement.
* Participants with previous administration of a gamma secretase inhibitor.
* Participants with concomitant administration of a strong CYP3A4 inhibitor or inducer.


* Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
* Participants who have received prior therapy with an anti-programmed death-1 (anti-PD-1), anti-PD-1-ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD-L2) agent.
* Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. Use of inhaled steroids, local injection of steroids, and steroid eye drops are allowed.


* Participants with Severe hypersensitivity to Isatuximab-irfc or to any of its excipients.
* Participants with prior treatment with other anti-CD38 monoclonal antibody within 6 months of the first dose of study drug treatment.
* Participants with known intolerance or hypersensitivity to infused proteins products, sucrose, histidine, and polysorbate 80.


* Participants with active or history of venous thromboembolism within the past 3 months.
* Participants with evidence of active mucosal or internal bleeding.
* Participants with contraindications to or are unwilling to undergo protocol-required anti-thrombotic prophylaxis or unable to tolerate antithrombolitic prophalaxis.


\- Participants who discontinued prior treatment with lenalidomide due to intolerable adverse events.


\- Participants who discontinued prior treatment with pomalidomide due to intolerable adverse events.


* Pregnant or lactating female or female who are interrupting lactation.
* Previously diagnosed with interstitial lung disease or current complication of interstitial lung disease.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

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GSK Investigational Site

Atlanta, Georgia, United States

Site Status

GSK Investigational Site

Indianapolis, Indiana, United States

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GSK Investigational Site

Boston, Massachusetts, United States

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GSK Investigational Site

Grand Rapids, Michigan, United States

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GSK Investigational Site

Madison, Wisconsin, United States

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GSK Investigational Site

Fitzroy, Victoria, Australia

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GSK Investigational Site

Melbourne, Victoria, Australia

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GSK Investigational Site

Porto Alegre, , Brazil

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GSK Investigational Site

Salvador, , Brazil

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GSK Investigational Site

São Paulo, , Brazil

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Vancouver, British Columbia, Canada

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Halifax, Nova Scotia, Canada

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GSK Investigational Site

Toronto, Ontario, Canada

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GSK Investigational Site

Lille, , France

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GSK Investigational Site

Villejuif, , France

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GSK Investigational Site

Frankfurt, , Germany

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Hamburg, , Germany

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Kiel, , Germany

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Leipzig, , Germany

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Athens, , Greece

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Mexico City, , Mexico

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Leeuwarden, , Netherlands

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Utrecht, , Netherlands

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Oslo, , Norway

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Gdansk, , Poland

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Katowice, , Poland

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Lodz, , Poland

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Lublin, , Poland

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GSK Investigational Site

Moscow, , Russia

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Incheon, , South Korea

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GSK Investigational Site

Seoul, , South Korea

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GSK Investigational Site

Seoul, , South Korea

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GSK Investigational Site

Seoul, , South Korea

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GSK Investigational Site

Ulsan, , South Korea

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GSK Investigational Site

Badalona, , Spain

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GSK Investigational Site

Madrid, , Spain

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GSK Investigational Site

Madrid, , Spain

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GSK Investigational Site

Madrid, , Spain

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GSK Investigational Site

PamplonaNavarra, , Spain

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Pozuelo de AlarcOn Madr, , Spain

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GSK Investigational Site

Falun, , Sweden

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GSK Investigational Site

Stockholm, , Sweden

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Countries

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Israel Japan United States Australia Brazil Canada France Germany Greece Mexico Netherlands Norway Poland Russia South Korea Spain Sweden

References

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Hosoya H, Sidana S. Antibody-Based Treatment Approaches in Multiple Myeloma. Curr Hematol Malig Rep. 2021 Apr;16(2):183-191. doi: 10.1007/s11899-021-00624-6. Epub 2021 Mar 17.

Reference Type DERIVED
PMID: 33730360 (View on PubMed)

Nooka AK, Weisel K, van de Donk NW, Routledge D, Otero PR, Song K, Quach H, Callander N, Minnema MC, Trudel S, Jackson NA, Ahlers CM, Im E, Cheng S, Smith L, Hareth N, Ferron-Brady G, Brouch M, Montes de Oca R, Paul S, Holkova B, Gupta I, Kremer BE, Richardson P. Belantamab mafodotin in combination with novel agents in relapsed/refractory multiple myeloma: DREAMM-5 study design. Future Oncol. 2021 Jun;17(16):1987-2003. doi: 10.2217/fon-2020-1269. Epub 2021 Mar 8.

Reference Type DERIVED
PMID: 33682447 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Other Identifiers

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208887

Identifier Type: -

Identifier Source: org_study_id