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

A Phase I/II, Randomized, Open-label Platform Study Utilizing a Master Protocol to Study Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Anti-Cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) - DREAMM 5

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04126200

Acronym

DREAMM5

Enrollment

208

Registered

2019-10-15

Start date

2019-10-07

Completion date

2027-03-11

Last updated

2025-11-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Multiple Myeloma

Keywords

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

Brief summary

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.

Interventions

DRUGBelantamab mafodotin

Belantamab mafodotin will be administered.

DRUGGSK3174998

GSK3174998 will be administered.

DRUGFeladilimab

feladilimab will be administered.

DRUGNirogacestat

Nirogacestat will be administered.

DRUGDostarlimab

Dostarlimab will be administered.

DRUGIsatuximab

Isatuximab will be administered.

DRUGLenalidomide

Lenalidomide will be administered.

DRUGDexamethasone

Dexamethasone will be administered.

DRUGPomalidomide

Pomalidomide will be administered.

Study design

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

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.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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. Inclusion Criteria Specific to Sub-study 6,7, and 8: * 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. Inclusion Criteria Specific to Sub-study 8: \- 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. Additional

Design outcomes

Primary

Measure	Time frame	Description
DE Phase: Number of participants achieving dose limiting toxicities (DLT)	Up to 12 months	An event is considered to be a DLT if the event occurs within the first 28 days of treatment and meets protocol defined DLT criteria.
DE Phase: Number of participants with adverse events (AEs) and serious adverse events (SAEs)	Up to 12 months	AEs and SAEs will be collected.
DE Phase: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters	Up to 12 months	Blood and urine samples will be collected to evaluate hematology, clinical chemistry and urinalysis lab parameters.
CE Phase: Number of participants achieving Overall Response Rate (ORR)	Up to 36 months	ORR is defined as the percentage of participants with a Partial response (PR) or better, according to the International Myeloma Working Group (IMWG) Response Criteria.

Secondary

Measure	Time frame	Description
DE Phase: Number of participants achieving Very Good Partial Response (VGPR)	Up to 12 months	Number of participants with VGPR according to IMWG criteria will be analyzed.
CE Phase: Number of participants achieving VGPR	Up to 36 months	Number of participants with VGPR according to IMWG criteria will be analyzed.
DE Phase: Number of participants achieving Complete Response (CR)	Up to 12 months	Participants with CR according to IMWG criteria will be analyzed.
CE Phase: Number of participants achieving CR	Up to 36 months	Participants with CR according to IMWG criteria will be analyzed.
DE Phase: Number of participants achieving stringent Complete Response (sCR)	Up to 12 months	Participants with sCR according to IMWG criteria will be analyzed.
CE Phase: Number of participants achieving sCR	Up to 36 months	Participants with sCR according to IMWG criteria will be analyzed.
DE Phase: Belantamab mafodotin concentrations when administered in combination with anti-cancer treatments	Up to 12 months	Blood samples will be collected for concentrations of belantamab mafodotin.
CE Phase: Belantamab mafodotin concentrations when administered in combination with anti-cancer treatments	Up to 36 months	Blood samples will be collected for concentrations of belantamab mafodotin.
DE Phase: GSK3174998 concentration when administered in combination with belantamab mafodotin	Up to 12 months	Blood samples will be collected for concentrations of GSK3174998.
CE Phase: GSK3174998 concentration when administered in combination with belantamab mafodotin	Up to 36 months	Blood samples will be collected for concentrations of GSK3174998.
DE Phase: Feladilimab concentration when administered in combination with belantamab mafodotin	Up to 12 months	Blood samples will be collected for concentrations of feladilimab.
DE Phase: Number of participants with AESI for GSK3174998	Up to 12 months	AESIs will be collected.
CE Phase: Feladilimab concentration when administered in combination with belantamab mafodotin	Up to 36 months	Blood samples will be collected for concentrations of feladilimab.
DE Phase: Nirogacestat concentration when administered in combination with belantamab mafodotin	Up to 12 months	Blood samples will be collected for concentrations of nirogacestat.
CE Phase: Nirogacestat concentration when administered in combination with belantamab mafodotin	Up to 36 months	Blood samples will be collected for concentrations of nirogacestat.
DE Phase: Dostarlimab concentration when administered in combination with belantamab mafodotin	Up to 12 months	Blood samples will be collected for concentrations of dostarlimab.
CE Phase: Dostarlimab concentration when administered in combination with belantamab mafodotin	Up to 36 months	Blood samples will be collected for concentrations of dostarlimab.
DE Phase: Isatuximab concentration when administered in combination with belantamab mafodotin	Up to 12 months	Blood samples will be collected for concentrations of isatuximab.
CE Phase: Isatuximab concentration when administered in combination with belantamab mafodotin	Up to 36 months	Blood samples will be collected for concentrations of isatuximab.
DE Phase: Concentration of anti-drug antibodies (ADAs) against belantamab mafodotin when administered in combination with anti-cancer treatments	Up to 12 months	Blood samples for concentrations for ADAs will be collected.
CE Phase: Number of participants with AESI for GSK3174998	Up to 36 months	AESIs will be collected.
DE Phase: Number of participants with AESI for Feladilimab	Up to 12 months	AESIs will be collected.
CE Phase: Number of participants with AESI for Feladilimab	Up to 36 months	AESIs will be collected.
CE Phase: Concentration of ADAs against belantamab mafodotin when administered in combination with anti-cancer treatments	Up to 36 months	Blood samples for concentrations for ADAs will be collected.
DE Phase: Concentration of ADAs against GSK3174998 when administered in combination with belantamab mafodotin	Up to 12 months	Blood samples for concentrations for ADAs will be collected.
CE Phase: Concentration of ADAs against GSK3174998 when administered in combination with belantamab mafodotin	Up to 36 months	Blood samples for concentrations for ADAs will be collected.
DE Phase: Concentration of ADAs against feladilimab when administered in combination with belantamab mafodotin	Up to 12 months	Blood samples for concentrations for ADAs will be collected.
CE Phase: Concentration of ADAs against feladilimab when administered in combination with belantamab mafodotin	Up to 36 months	Blood samples for concentrations for ADAs will be collected.
DE Phase: Concentration of ADAs against dostarlimab when administered in combination with belantamab mafodotin	Up to 12 months	Blood samples for concentrations for ADAs will be collected.
CE Phase: Concentration of ADAs against dostarlimab when administered in combination with belantamab mafodotin	Up to 36 months	Blood samples for concentrations for ADAs will be collected.
DE Phase: Concentration of ADAs against isatuximab when administered in combination with belantamab mafodotin	Up to 12 months	Blood samples for concentrations for ADAs will be collected.
CE Phase: Concentration of ADAs against isatuximab when administered in combination with belantamab mafodotin	Up to 36 months	Blood samples for concentrations for ADAs will be collected.
DE Phase: Number of participants with adverse events of special interest (AESI) for belantamab mafodotin	Up to 12 months	AESIs will be collected.
CE Phase: Number of participants with AESI for belantamab mafodotin	Up to 36 months	AESIs will be collected.
DE Phase: Number of participants with AESI for Nirogacestat	Up to 12 months	AESIs will be collected.
CE Phase: Number of participants with AESI for Nirogacestat	Up to 36 months	AESIs will be collected.
DE Phase: Number of participants with AESI for Dostarlimab	Up to 12 months	AESIs will be collected.
CE Phase: Number of participants with AESI for Dostarlimab	Up to 36 months	AESIs will be collected.
DE Phase: Number of participants with AESI for Isatuximab	Up to 12 months	AESIs will be collected.
CE Phase: Number of participants with AESI for Isatuximab	Up to 36 months	AESIs will be collected.
DE Phase: Number of participants with abnormal ocular findings on ophthalmic examination	Up to 12 months	Ophthalmic examination will assess abnormal findings.
CE Phase: Number of participants with abnormal ocular findings on ophthalmic examination	Up to 36 months	Ophthalmic examination will assess abnormal findings.
CE Phase: Number of participants achieving Progression-free survival (PFS)	Up to 36 months	PFS is defined as the time from randomization until the earliest date of confirmed progressive disease (PD) per IMWG, or death due to any cause.
CE Phase: Duration of response (DoR)	Up to 36 months	DoR is defined as the time from first documented evidence or PR or better until progressive disease per IMWG or death due to progressive disease among participants who achieve confirmed partial response or better.
CE Phase: Time to response (TTR)	Up to 36 months	TTR is defined as the time between the date of randomization and the first documented evidence of response (PR or better), among participants who achieve a response (confirmed PR or better).
CE Phase: Number of participants achieving Overall survival (OS)	Up to 36 months	OS is defined as the time from randomization until death due to any cause.
DE Phase: Number of participants achieving ORR	Up to 12 months	ORR is defined as the percentage of participants with PR or better, according to the IMWG Response Criteria.
CE Phase: Number of participants with AEs leading to discontinuation	Up to 36 months	Number of participants with AEs leading to discontinuation will be evaluated.
CE Phase: Number of participants with dose reduction or delay	Up to 36 months	Number of participants with dose reduction or delay will be evaluated.
CE Phase: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters	Up to 36 months	Blood and urine samples will be collected to evaluate hematology, clinical chemistry and urinalysis lab parameters.
CE Phase: Number of participants with AEs and SAEs	Up to 36 months	AEs and SAEs will be collected.
CE Phase: Number of participants achieving Clinical Benefit Rate (CBR)	Up to 36 months	CBR is defined as the percentage of participants with a minimal response (MR) or better, according to IMWG response criteria.
DE Phase: Number of participants achieving Partial Response (PR)	Up to 12 months	Number of participants with PR according to IMWG criteria will be analyzed.
CE Phase: Number of participants achieving PR	Up to 36 months	Number of participants with PR according to IMWG criteria will be analyzed.

Countries

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

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 22, 2026