ANZCTR - Registration

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05714839

Registration number

NCT05714839

Ethics application status

Date submitted

27/01/2023

Date registered

6/02/2023

Date last updated

20/11/2024

Titles & IDs

Public title

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

Scientific 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

Secondary ID [1]

2022-501941-63-00

Secondary ID [2]

218670

Universal Trial Number (UTN)

Trial acronym

DREAMM-20

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Multiple Myeloma

Condition category

Condition code

Cancer

Other cancer types

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - Belantamab
Treatment: Drugs - Belantamab mafodotin
Treatment: Drugs - Belantamab and belantamab mafodotin

Experimental: Part 1: Dose escalation of belantamab monotherapy - Belantamab will be administered in participants with RRMM until progressive disease (PD)

Experimental: Part 2: Belantamab and belantamab mafodotin (delivered as separate drugs) dose range finding - Participants with RRMM will receive belantamab in combination with a fixed dose of belantamab mafodotin (delivered as separate drugs)

Experimental: Part 1b: Optional belantamab mafodotin - 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.

Treatment: Drugs: Belantamab
Belantamab will be administered.

Treatment: Drugs: Belantamab mafodotin
Belantamab mafodotin will be administered.

Treatment: Drugs: Belantamab and belantamab mafodotin
Belantamab and belantamab mafodotin used in combination (delivered as separate drugs) will be administered.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

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

Timepoint [1]

Up to 52 months

Primary outcome [2]

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

Timepoint [2]

Cycle 1 (Each cycle is of 28 days)

Primary outcome [3]

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

Timepoint [3]

Up to 52 months

Primary outcome [4]

Part 1 and 2: Number of Participants with ocular events by the modified Keratopathy Visual Acuity (mKVA) scale

Timepoint [4]

Up to 52 months

Primary outcome [5]

Part 2: Overall Response Rate (ORR)

Timepoint [5]

Up to 52 months

Secondary outcome [1]

Part 1: Observed Plasma Concentration of belantamab

Timepoint [1]

Up to 52 months

Secondary outcome [2]

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

Timepoint [2]

Up to 52 months

Secondary outcome [3]

Part 1: Maximum Concentration (Cmax) of belantamab

Timepoint [3]

Up to 52 months

Secondary outcome [4]

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

Timepoint [4]

Up to 52 months

Secondary outcome [5]

Part 1: Titers of ADA against belantamab

Timepoint [5]

Up to 52 months

Secondary outcome [6]

Part 1: Overall Response Rate (ORR)

Timepoint [6]

Up to 52 months

Secondary outcome [7]

Part 2: Duration of Response (DoR)

Timepoint [7]

Up to 52 months

Secondary outcome [8]

Part 2: Observed Plasma Concentration of Total belantamab

Timepoint [8]

Up to 52 months

Secondary outcome [9]

Part 2: Area Under the Curve (AUC) of Total belantamab

Timepoint [9]

Up to 52 months

Secondary outcome [10]

Part 1: Maximum Concentration (Cmax) of Total belantamab

Timepoint [10]

Up to 52 months

Secondary outcome [11]

Part 2: Observed Plasma Concentration of belantamab mafodotin antibody-drug conjugate (ADC)

Timepoint [11]

Up to 52 months

Secondary outcome [12]

Part 2: Area Under the Curve (AUC) of belantamab mafodotin (ADC)

Timepoint [12]

Up to 52 months

Secondary outcome [13]

Part 1: Maximum Concentration (Cmax) of belantamab mafodotin (ADC)

Timepoint [13]

Up to 52 months

Secondary outcome [14]

Part 2: Observed Plasma Concentration of Cys-Monomethyl Auristatin-F (Cys-mcMMAF)

Timepoint [14]

Up to 52 months

Secondary outcome [15]

Part 2: Area Under the Curve (AUC) of Cys-mcMMAF

Timepoint [15]

Up to 52 months

Secondary outcome [16]

Part 1: Maximum Concentration (Cmax) of Cys-mcMMAF

Timepoint [16]

Up to 52 months

Secondary outcome [17]

Part 2: Number of Participants with ADAs against belantamab and belantamab mafodotin

Timepoint [17]

Up to 52 months

Secondary outcome [18]

Part 2: Titers of ADAs against belantamab and belantamab mafodotin

Timepoint [18]

Up to 52 months

Eligibility

Key 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 international myeloma working group (IMWG).

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) and have confirmed progression on or following the last line of treatment.
* Participants with a history of Autologous stem cell transplant (ASCT) are eligible for study participation provided the following eligibility criteria are met:

1. transplant was greater than (>)100 days prior to screening.
2. no active infection(s)
* Eastern cooperative oncology group-performance status (ECOG-PS) of 0 to 2.
* Measurable disease defined as at least ONE of the following:

1. Serum M-protein concentration greater than (>=) 0.5 gram (g)/ deciliter (dL) (>=5 gram/liter [g/L])
2. Urine M-protein excretion >=200 mg/24 hours (>=0.2 g/24 hours)
3. 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.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key 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.
* 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).
* Evidence of cardiovascular risk
* Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to belantamab / belantamab mafodotin or any of the components of the study treatment. History of severe hypersensitivity to other Monoclonal antibodies (mAbs).
* Active infection requiring antibiotic, antiviral, or antifungal treatment.
* Known Human immunodeficiency virus (HIV) infection, unless the participant can meet specific criteria.
* Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction.
* Participants with Hepatitis B virus (HBV) or Hepatitis C virus (HCV) will be excluded unless specific criteria can be met
* 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 are eligible
* Refractory to belantamab mafodotin (confirmed PD as per IMWG criteria while on belantamab mafodotin therapy or within 60 days of completing that treatment). Prior belantamab mafodotin is allowed if it was discontinued due to toxicity which subsequently resolved.
* Prior radiotherapy within 2 weeks of start of study therapy.
* Plasmapheresis within 7 days prior to the first dose of study drug.
* Prior allogeneic transplant is prohibited.
* Participants who have received prior Chimeric Antigen Receptor T-cell therapy (CAR-T) therapy with lymphodepletion with chemotherapy within 3 months of screening.
* Any major surgery (other than bone-stabilizing surgery) within 2 weeks of first dose or has not recovered fully from surgery.
* Prior treatment with a mAb within 30 days of receiving the first dose of study drugs, or treatment with an investigational agent or approved systemic anti-myeloma therapy (including systemic steroids) within 14 days or 5 half-lives of receiving the first dose of study drugs, whichever is longer.
* Has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including Granulocyte colony stimulating factor (G-CSF), Granulocyte-macrophage colony-stimulating factor (GMCSF), recombinant erythropoietin) or any thrombopoietin receptor agonists within 2 weeks before the first dose of study drug.
* Participants must not receive live/live attenuated vaccines within 30 days prior to first dose of study treatment or whilst receiving belantamab for at least 70 days following last study 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.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Other

Other design features

Phase

Phase 1

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

31/05/2023

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

19/09/2028

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC,WA

Recruitment hospital [1]

GSK Investigational Site - Fitzroy

Recruitment hospital [2]

GSK Investigational Site - Nedlands

Recruitment postcode(s) [1]

3065 - Fitzroy

Recruitment postcode(s) [2]

6009 - Nedlands

Recruitment outside Australia

Country [1]

Argentina

State/province [1]

Ciudadela

Country [2]

Argentina

State/province [2]

Viedma

Country [3]

Brazil

State/province [3]

Joinville

Country [4]

Brazil

State/province [4]

Salvador

Country [5]

Brazil

State/province [5]

SAo Paulo

Country [6]

Japan

State/province [6]

Aomori

Country [7]

Japan

State/province [7]

Osaka

Country [8]

Korea, Republic of

State/province [8]

Seoul

Country [9]

Poland

State/province [9]

Gdansk

Country [10]

Poland

State/province [10]

Lublin

Country [11]

Taiwan

State/province [11]

Changhua

Country [12]

Taiwan

State/province [12]

Taipei

Country [13]

Turkey

State/province [13]

Istanbul

Country [14]

Turkey

State/province [14]

Kayseri

Country [15]

United Kingdom

State/province [15]

Leicester

Country [16]

United Kingdom

State/province [16]

Oxford

Country [17]

United Kingdom

State/province [17]

Plymouth

Funding & Sponsors

Primary sponsor type

Commercial sector/industry

Name

GlaxoSmithKline

Address

Country

Ethics approval

Ethics application status

Summary

Brief summary

The study consists of two parts: Part 1 The primary purpose of this part aims to evaluate the safety, tolerability, and clinical activity of escalating doses of single agent belantamab 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 belantamab (delivered as separate drugs) in participants with RRMM who have received at least 3 prior therapies (4L+).

Trial website

https://clinicaltrials.gov/study/NCT05714839

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

GSK Clinical Trials

Address

GlaxoSmithKline

Country

Phone

Fax

Contact person for public queries

Name

US GSK Clinical Trials Call Center

Address

Country

Phone

877-379-3718

Fax

[email protected]

Contact person for scientific queries

Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05714839

Trial Review

Registering a new trial?

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05714839