DREAMM-20: A Study to Investigate the Safety and Efficacy of Belantamab for the Treatment of Multiple Myeloma When Used as Monotherapy and in Combination Treatments

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05714839

Collaborator

(none)

124

Enrollment

Arms

51.9

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The study consists of three parts

Part 1: The primary purpose of this part is to determine the safety, and recommended part 2 dose of belantamab (bela) in participants with relapsed or refractory multiple myeloma (RRMM).
Part 2: The primary purpose of this part is to determine safety, tolerability and percentage of adverse events (AEs) that happen to eyes in participants with RRMM treated with bela in combination with other treatments.
Part 3: The primary objective of this part is to assess the safety, tolerability and rate of ocular AEs in participants with transplant-ineligible newly diagnosed multiple myeloma (TI-NDMM) treated with either belantamab mafodotin (belamaf) or bela in combination with other treatments.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Bela Drug: Belamaf Drug: Lenalidomide Drug: Dexamethasone Drug: Standard of Care	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

124 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1/2 Open-label, Multicentre, Dose Escalation and Expansion Study to Investigate the Safety, Tolerability, and Clinical Activity of Belantamab as Monotherapy and in Combination With Other Treatments in Participants With Multiple Myeloma

Anticipated Study Start Date :

Feb 28, 2023

Anticipated Primary Completion Date :

Jun 28, 2027

Anticipated Study Completion Date :

Jun 28, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1 - Dose Escalation Phase in Participants with RRMM Bela will be administered in participants with RRMM until progressive disease (PD). Participants may switch to Belamaf in case of PD.	Drug: Bela Bela will be administered. Other Names: Belantamab GSK2857914 Drug: Belamaf Belamaf will be administered. Other Names: Belantamab mafodotin GSK2857916 BLENREP
Experimental: Part 2 - Combination Treatments in Participants with RRMM Participants with RRMM will receive Bela-xRd and Belamaf-xRd. The combination treatment xRd includes lenalidomide (R) and dexamethasone (d). x will be either a standard of care (SoC) or an emerging treatment for Multiple Myeloma.	Drug: Bela Bela will be administered. Other Names: Belantamab GSK2857914 Drug: Belamaf Belamaf will be administered. Other Names: Belantamab mafodotin GSK2857916 BLENREP Drug: Lenalidomide Lenalidomide will be administered. Drug: Dexamethasone Dexamethasone will be administered. Drug: Standard of Care Either standard of care (SoC) or an emerging treatment for Multiple Myeloma will be administered
Experimental: Part 3 - Combination Treatments in Participants with TI-NDMM Participants with TI-NDMM will receive Bela-xRd and Belamaf-xRd. The combination treatment xRd includes lenalidomide (R) and dexamethasone (d). x will be either a standard of care (SoC) or an emerging treatment for Multiple Myeloma.	Drug: Bela Bela will be administered. Other Names: Belantamab GSK2857914 Drug: Belamaf Belamaf will be administered. Other Names: Belantamab mafodotin GSK2857916 BLENREP Drug: Lenalidomide Lenalidomide will be administered. Drug: Dexamethasone Dexamethasone will be administered. Drug: Standard of Care Either standard of care (SoC) or an emerging treatment for Multiple Myeloma will be administered

Arm

Intervention/Treatment

Experimental: Part 1 - Dose Escalation Phase in Participants with RRMM

Bela will be administered in participants with RRMM until progressive disease (PD). Participants may switch to Belamaf in case of PD.

Drug: Bela

Bela will be administered.

Other Names:

Belantamab

GSK2857914

Drug: Belamaf

Belamaf will be administered.

Other Names:

Belantamab mafodotin

GSK2857916 BLENREP

Experimental: Part 2 - Combination Treatments in Participants with RRMM

Participants with RRMM will receive Bela-xRd and Belamaf-xRd. The combination treatment xRd includes lenalidomide (R) and dexamethasone (d). x will be either a standard of care (SoC) or an emerging treatment for Multiple Myeloma.

Drug: Bela

Bela will be administered.

Other Names:

Belantamab

GSK2857914

Drug: Belamaf

Belamaf will be administered.

Other Names:

Belantamab mafodotin

GSK2857916 BLENREP

Drug: Lenalidomide

Lenalidomide will be administered.

Drug: Dexamethasone

Dexamethasone will be administered.

Drug: Standard of Care

Either standard of care (SoC) or an emerging treatment for Multiple Myeloma will be administered

Experimental: Part 3 - Combination Treatments in Participants with TI-NDMM

Participants with TI-NDMM will receive Bela-xRd and Belamaf-xRd. The combination treatment xRd includes lenalidomide (R) and dexamethasone (d). x will be either a standard of care (SoC) or an emerging treatment for Multiple Myeloma.

Drug: Bela

Bela will be administered.

Other Names:

Belantamab

GSK2857914

Drug: Belamaf

Belamaf will be administered.

Other Names:

Belantamab mafodotin

GSK2857916 BLENREP

Drug: Lenalidomide

Lenalidomide will be administered.

Drug: Dexamethasone

Dexamethasone will be administered.

Drug: Standard of Care

Either standard of care (SoC) or an emerging treatment for Multiple Myeloma will be administered

Outcome Measures

Primary Outcome Measures

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, 2 and 3: Number of Participants with Worst Case Grade Change from Baseline in Laboratory and Vital Sign Parameters [Up to 52 months]
Part 2 and 3: Number of Participants with Corneal Adverse Events (CAEs) [Up to 52 months]

Secondary Outcome Measures

Part 1, 2 and 3: Observed Plasma Concentration of Bela [Up to 52 months]
Part 1, 2 and 3: Area Under the Curve (AUC) of Bela [Up to 52 months]
Part 1, 2 and 3: Maximum Concentration (Cmax) of Bela [Up to 52 months]
Part 1, 2 and 3: Number of Participants with Anti-Drug Antibodies (ADA) against Bela [Up to 52 months]
Part 1, 2 and 3: Titers of ADA against Bela [Up to 52 months]
Part 2 and 3: Number of Participants with ADAs against Belamaf [Up to 52 months]
Part 2 and 3: Titers of ADAs against Belamaf [Up to 52 months]
Part 1, 2 and 3: Objective Response Rate (ORR) [Up to 52 months]
ORR is defined as the percentage of participants with a confirmed Partial Response (PR) or better [i.e., PR, Very Good Partial Response (VGPR), Complete Response (CR), Stringent Complete Response (sCR)] as per International Myeloma Working Group (IMWG) criteria.
Part 2 and 3: Stringent Complete Response (sCR) Rate [Up to 52 months]
sCR is defined as the percentage of participants with CR plus normal free light chain ratio and absence of clonal cells in the bone marrow (BM) as per IMWG criteria.
Part 2 and 3: Complete Response (CR) Rate [Up to 52 months]
CR rate is defined as the percentage of participants with a confirmed CR or better (i.e., CR, sCR) as per IMWG criteria.
Part 2 and 3: Very Good Partial Response (VGPR) Rate [Up to 52 months]
VGPR rate is defined as the percentage of participants with a confirmed VGPR or better (i.e., VGPR, CR, sCR) as per IMWG criteria.
Part 2 and 3: Observed Plasma Concentration of Belamaf [Up to 52 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 IMWG, and measurable disease.
PART 1: Participants who have received at least 3 prior lines of anti-myeloma treatments, and have already received an immunomodulating agent, a proteasome inhibitor, and an anti-CD38 mAb (unless contraindicated or unavailable). Lines of therapy are defined by consensus panel of the International Myeloma Workshop.
PART 2: Participants who meet all of the following:
Have undergone Autologous stem cell transplant (ASCT) or are considered transplant ineligible
Have been previously treated with at least ONE prior line of MM therapy
Have documented disease progression during or after their most recent therapy
PART 3: Participants who meet both of the following:
NDMM with a requirement for treatment as documented per IMWG criteria
Not considered a candidate for high dose chemotherapy with ASCT due to:

Age ≥ 65 years OR
Age 18-65 years with presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT or who refuse high-dose chemotherapy with ASCT as an initial treatment.

Participants capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and protocol.

Exclusion Criteria:

Diagnosis of primary Amyloid Light chain (AL) Amyloidosis, active Polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes (POEMS) syndrome, primary plasma cell leukemia.
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.
Active infection requiring antibiotic, antiviral, or antifungal treatment.
Known, current drug or alcohol abuse.
Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this trial, unless prospective Independent Review Board (IRB) approval (by chair or designee) is allowing exception to this criterion for a specific participant.