Belantamab Mafodotin Plus Pomalidomide and Dexamethasone (Pd) Versus Bortezomib Plus Pd in Relapsed/Refractory Multiple Myeloma

Multiple Myeloma Clinical Trial

— DREAMM 8  

Official title:

A Phase III, Multicenter, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin in Combination With Pomalidomide and Dexamethasone (B-Pd) Versus Pomalidomide Plus Bortezomib and Dexamethasone (PVd) in Participants With Relapsed/Refractory Multiple Myeloma (DREAMM 8)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04484623
• Other study ID #: 207499
• Secondary ID: 2018-004354-21
• Status: Recruiting
• Phase: Phase 3
• Start date: October 1, 2020
• Est. completion date: May 1, 2029

Study information

• Verified date: May 2024
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy and safety of belantamab mafodotin in combination with pomalidomide and dexamethasone (Arm A) compared with that of combination of pomalidomide, bortezomib and dexamethasone (Arm B) in participants with relapsed/refractory multiple myeloma (RRMM).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 357
• Est. completion date: May 1, 2029
• Est. primary completion date: January 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Capable of giving signed informed consent.
• Male or female, 18 years or older.
• Have a confirmed diagnosis of multiple myeloma (MM) as defined by the International Myeloma Working Group (IMWG) criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Have been previously treated with at least 1 prior line of MM therapy including a lenalidomide-containing regimen and must have documented disease progression during or after their most recent therapy. (Participants treated with lenalidomide =10 mg daily for at least 2 consecutive cycles are eligible).
• Must have at least 1 aspect of measurable disease defined as one of the following;

1. Urine M-protein excretion greater than or equal to (=)200 milligrams (mg) per 24-hour, or

2. Serum M-protein concentration =0.5 grams/deciliters (g/dL) (=5.0 g/liter [L]), or

3. Serum free light chain (FLC) assay: involved FLC level =10 mg/dL (=100 mg/L) and an abnormal serum free light chain ratio (less than [<]0.26 or greater than [>]1.65) only if participant has no measurable urine or serum M spike.

• Have undergone autologous stem cell transplant (ASCT) or are considered transplant ineligible. Participants with a history of ASCT are eligible for study participation provided the following eligibility criteria are met: a. ASCT was >100 days prior to the first dose of study medication. b. No active bacterial, viral, or fungal infection(s) present
• All prior treatment-related toxicities (defined by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 5.0) must be less than or equal to (=)Grade 1 at the time of enrolment, except for alopecia.
• Adequate organ system functions as mentioned in the protocol.
• Male and female participants agree to abide by protocol-defined contraceptive requirements.

Exclusion Criteria:

• Active plasma cell leukemia, symptomatic amyloidosis or active polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, and skin changes (POEMS) syndrome at the time of screening.
• Prior allogeneic SCT.
• Systemic anti-myeloma therapy (including chemotherapy and systemic steroids) within 14 days or five half-lives (whichever is shorter) preceding the first dose of study drug; prior treatment with a monoclonal antibody drug within 30 days of receiving the first dose of study drugs.
• Plasmapheresis within 7 days prior to the first dose of study drug.
• Received prior treatment with or intolerant to pomalidomide.
• Received prior Beta cell maturation antigen (BCMA) targeted therapy.
• Intolerant to bortezomib or refractory to bortezomib (for example; participant experienced progressive disease during treatment, or within 60 days of completing treatment, with a bortezomib-containing regimen of 1.3 mg/meter square [m^2] twice weekly).
• Evidence of cardiovascular risk including any of the following;

1. Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram abnormalities including second degree (Mobitz type II) or third degree atrioventricular (AV) block.

2. Recent history within (3 months of screening) of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting .

3. Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system

4. Uncontrolled hypertension.

• Any major surgery within the last 4 weeks.
• Previous or concurrent invasive malignancy other than multiple myeloma, except:

1. The disease must be considered medically stable for at least 2 years; or

2. The participant must not be receiving active therapy, other than hormonal therapy for this disease.

• Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to belantamab mafodotin or drugs chemically related to belantamab mafodotin, or any of the components of the study treatment.
• Evidence of active mucosal or internal bleeding.
• Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice.
• Active infection requiring treatment.
• Known or active human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C will be excluded unless the protocol-defined criteria are met.
• Presence of active renal conditions (such as infection, severe renal impairment requiring dialysis or any other condition that could affect participant's safety).
• Ongoing Grade 2 peripheral neuropathy with pain within 14 days prior to randomization or =Grade 3 peripheral neuropathy.
• Active or history of venous and arterial thromboembolism within the past 3 months.
• Contraindications to or unwilling to undergo protocol-required anti-thrombotic prophylaxis.
• Current corneal disease except for mild punctate keratopathy.
• Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including laboratory abnormalities) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures.
• Pregnant or lactating female.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Belantamab mafodotin
Humanized anti-B-cell maturation antigen (BCMA) antibody/drug conjugate will be administered.
• Pomalidomide
Immunomodulatory drug (IMiD) will be administered.
• Dexamethasone
Synthetic glucocorticoid with anti-tumor activity will be administered.
• Bortezomib
Proteasome Inhibitor will be administered.

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Adelaide	South Australia
Australia	GSK Investigational Site	Benowa	Queensland
Australia	GSK Investigational Site	Canberra	Australian Capital Territory
Australia	GSK Investigational Site	Darlinghurst	New South Wales
Australia	GSK Investigational Site	Fitzroy	Victoria
Australia	GSK Investigational Site	Gosford	New South Wales
Australia	GSK Investigational Site	Heidelberg	Victoria
Australia	GSK Investigational Site	Malvern	Victoria
Australia	GSK Investigational Site	Nedlands	Western Australia
Australia	GSK Investigational Site	Port Macquarie	New South Wales
Australia	GSK Investigational Site	South Brisbane	Queensland
Brazil	GSK Investigational Site	Curitiba
Brazil	GSK Investigational Site	Joinville	Santa Catarina
Brazil	GSK Investigational Site	São Paulo
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Changchun	Jilin
China	GSK Investigational Site	Changsha	Hunan
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Hangzhou	Zhejiang
China	GSK Investigational Site	Nanchang	Jiangxi
China	GSK Investigational Site	Shenyang	Liaoning
China	GSK Investigational Site	Shenzhen	Guangdong
China	GSK Investigational Site	Tianjin
China	GSK Investigational Site	Wuhan	Hubei
China	GSK Investigational Site	Xuzhou	Jiangsu
Czechia	GSK Investigational Site	Brno
Czechia	GSK Investigational Site	Hradec Kralove
Czechia	GSK Investigational Site	Praha 2
France	GSK Investigational Site	Marseille Cedex 9
France	GSK Investigational Site	Toulouse cedex 9
France	GSK Investigational Site	Vandeouvre-les-Nancy
Germany	GSK Investigational Site	Jena	Thueringen
Germany	GSK Investigational Site	Mainz	Rheinland-Pfalz
Germany	GSK Investigational Site	Tuebingen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Wuerzburg	Bayern
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Ioannina
Greece	GSK Investigational Site	Thessaloniki
Israel	GSK Investigational Site	Ashdod
Israel	GSK Investigational Site	Haifa
Israel	GSK Investigational Site	Jerusalem
Israel	GSK Investigational Site	Kfar Saba
Israel	GSK Investigational Site	Nahariya
Israel	GSK Investigational Site	Petach-Tikva
Israel	GSK Investigational Site	Tel Aviv
Italy	GSK Investigational Site	Bologna	Emilia-Romagna
Italy	GSK Investigational Site	Milano
Italy	GSK Investigational Site	Pavia	Lombardia
Italy	GSK Investigational Site	Roma	Lazio
Japan	GSK Investigational Site	Aichi
Japan	GSK Investigational Site	Chiba
Japan	GSK Investigational Site	Ehime
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukushima
Japan	GSK Investigational Site	Gunma
Japan	GSK Investigational Site	Gunma
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Iwate
Japan	GSK Investigational Site	Kumamoto
Japan	GSK Investigational Site	Kyoto
Japan	GSK Investigational Site	Okayama
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Saitama
Japan	GSK Investigational Site	Tokushima
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tottori
Japan	GSK Investigational Site	Yamagata
Korea, Republic of	GSK Investigational Site	Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Hwasun-gun, Jeollanam-do
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Ulsan
New Zealand	GSK Investigational Site	Auckland
New Zealand	GSK Investigational Site	Auckland
New Zealand	GSK Investigational Site	Dunedin
New Zealand	GSK Investigational Site	Grafton, Auckland
New Zealand	GSK Investigational Site	Hamilton
New Zealand	GSK Investigational Site	Tauranga
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Wroclaw
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Novosibirsk
Russian Federation	GSK Investigational Site	Saint Petersburg
Russian Federation	GSK Investigational Site	Samara
Russian Federation	GSK Investigational Site	Sochi
Russian Federation	GSK Investigational Site	St'Petersburg
Russian Federation	GSK Investigational Site	St. Petersburg
Spain	GSK Investigational Site	Badalona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Gijon
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid	Navarra
Spain	GSK Investigational Site	Móstoles	Madrid
Spain	GSK Investigational Site	Murcia
Spain	GSK Investigational Site	Palma de Mallorca
Spain	GSK Investigational Site	Pamplona
Spain	GSK Investigational Site	Pozuelo De Alarcón/Madrid
Spain	GSK Investigational Site	Salamanca
Spain	GSK Investigational Site	Sevilla
Spain	GSK Investigational Site	Valencia
Turkey	GSK Investigational Site	Ankara
Turkey	GSK Investigational Site	Ankara
Turkey	GSK Investigational Site	Ankara
Turkey	GSK Investigational Site	Izmir
Turkey	GSK Investigational Site	Izmir
Turkey	GSK Investigational Site	Kocaeli
Turkey	GSK Investigational Site	Mersin
Turkey	GSK Investigational Site	Samsun
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Plymouth
United Kingdom	GSK Investigational Site	Southampton	Hampshire
United Kingdom	GSK Investigational Site	Stoke-on-Trent	Staffordshire
United Kingdom	GSK Investigational Site	Sutton	Surrey
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Fort Myers	Florida
United States	GSK Investigational Site	Kansas City	Missouri
United States	GSK Investigational Site	Nashville	Tennessee
United States	GSK Investigational Site	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  China,  Czechia,  France,  Germany,  Greece,  Israel,  Italy,  Japan,  Korea, Republic of,  New Zealand,  Poland,  Russian Federation,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)	PFS will be defined as the time from the randomization until the earliest date of progressive disease (PD) based on Independent Review Committee (IRC) assessment per International Myeloma Working Group (IMWG) criteria, or death due to any cause	Up to 84 months
Secondary	Duration of response (DoR)	DoR will be defined as the time from first documented evidence of partial response or better until progressive disease (PD) or death due to any cause. Response will be based on IRC-assessment per IMWG criteria.	Up to 84 months
Secondary	Minimal residual disease (MRD) negativity rate	MRD negativity rate will be defined as the percentage of participants who achieve MRD negative status (as assessed by next-generation sequencing (NGS) at 10^5 threshold) at least once during the time of confirmed CR or better response, based on IRC assessment per IMWG.	Up to 84 months
Secondary	Overall survival (OS)	OS will be defined as the interval of time from randomization to the date of death due to any cause.	Up to 84 months
Secondary	Overall response rate (ORR)	ORR will be defined as the percentage of participants with a confirmed partial response or better (i.e., PR, VGPR, CR, and sCR) based on IRC-assessment per IMWG criteria.	Up to 84 months
Secondary	Complete response rate (CRR)	CRR will be defined as the percentage of participants with a confirmed complete response or better (i.e., CR and stringent complete respone (sCR) based on IRC-assessment per IMWG criteria.	Up to 84 months
Secondary	Very good partial response (VGPR) or better rate	VGPR will be the defined as the percentage of participants with a confirmed VGPR or better (i.e., VGPR, CR, and sCR) based on IRC-assessment per IMWG criteria.	Up to 84 months
Secondary	Time to best response (TTBR)	TTBR will be defined as the interval of time between the date of randomization and the earliest date of achieving best response among participants with a confirmed PR or better based on IRC-assessment per IMWG.	Up to 84 months
Secondary	Time to response (TTR)	TTR 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 (i.e., confirmed PR or better) based on IRC-assessment per IMWG.	Up to 84 months
Secondary	Time to progression (TTP)	TTP defined as the time from randomization until the earliest date of PD based on IRC-assessment per IMWG criteria, or death due to PD.	Up to 84 months
Secondary	Progression-free survival on subsequent line of therapy (PFS2)	PFS2 defined as time from randomization to disease progression (investigator-assessed response) after initiation of new anti-myeloma therapy or death from any cause, whichever is earlier. If disease progression after new anti-myeloma therapy cannot be measured, a PFS event is defined as the date of discontinuation of new anti-myeloma therapy, or death from any cause, whichever is earlier.	Up to 84 months
Secondary	Number of participants with adverse events (AEs) and serious adverse events (SAEs)		Up to 84 months
Secondary	Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters		Up to 84 months
Secondary	Number of participants with abnormal ocular findings on ophthalmic examination		Up to 84 months
Secondary	Plasma concentrations of belantamab mafodotin at indicated time points		Up to 84 months
Secondary	Plasma concentrations of monomethyl auristatin-F with a cysteine linker (cys-mcMMAF) at indicated time points		Up to 84 months
Secondary	Maximum observed concentration (Cmax) for pomalidomide		Up to 24 hours
Secondary	Time of Cmax (Tmax) for pomalidomide		Up to 24 hours
Secondary	Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC[0-t]) for pomalidomide		Up to 24 hours
Secondary	Number of participants with positive anti-drug antibodies (ADAs) against belantamab mafodotin		Up to 84 months
Secondary	Titers of ADAs against belantamab mafodotin		Up to 84 months
Secondary	Number of participants with maximum post-baseline changes in patient-reported outcome version of the common terminology criteria for adverse events (PRO-CTCAE) scores for each item attribute	PRO-CTCAE questionnaire assesses side effect symptoms in cancer clinical trial. Impacts of the side effects will be assessed using PRO-CTCAE score.	Baseline and up to 84 months
Secondary	Change from Baseline in health related quality of life (HRQoL) as measured by European Organization for Research and Treatment of Cancer Quality of life Questionnaire 30-item core module (EORTC QLQ-C30)	EORTC Quality of Life questionnaire QLQ-C30 on a scale of 0-100. Lower scores correlate with worse quality of life and higher scores correlate with better quality of life.	Baseline and up to 84 months
Secondary	Change from Baseline in HRQoL as measured by EORTC item library 52 (IL52)	EORTC QLQ- 20-item Multiple Myeloma Module (MY20) questionnaire will be referred to as the EORTC IL52. Only disease symptoms domain will be assessed. A high score represents a high level of symptoms or problems.	Baseline and up to 84 months
Secondary	Change from Baseline in HRQoL as measured by EORTC QLQ-20-item Multiple Myeloma Module (MY20)	EORTC QLQ-MY20 is a questionnaire which will evaluate disease symptoms. In EORTC QLQ-MY20, domain scores will be averaged and will be transformed linearly to a score ranging from 0 to 100. Higher score represents high level of symptomatology or problems.	Baseline and up to 84 months