Phase 3 study of belantamab mafodotin, lenalidomide, and dexamethasone (BRd) versus daratumumab, lenalidomide, and dexamethasone (DRd) in participants with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

30 Apr 2025 → ongoing

Decision date (initial)

2025-04-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

GlaxoSmithKline Research & Development Limited

External identifiers

EU CT number

2024-516030-35-00

ClinicalTrials.gov

NCT06679101

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Evaluate the efficacy and safety of BRd compared with DRd in participants with TI-NDMM

Secondary objectives 6

1. To further evaluate the clinical efficacy of BRd compared with DRd in participants with TI-NDMM
2. To evaluate the clinical efficacy of BRd compared with DRd in participants with TI-NDMM
3. To evaluate the safety and tolerability of BRd vs. DRd in participants with TI-NDMM
4. To evaluate the safety and tolerability of the study intervention based on self-reported symptomatic adverse effects in participants with TI-NDMM
5. To evaluate and compare changes in symptoms and impact on function and HRQoL in participants with TI-NDMM
6. To characterize the exposure to belantamab mafodotin when administered in combination with lenalidomide/dexamethasone in participants with TI-NDMM

Conditions and MedDRA coding

Multiple myeloma

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Is at least 18 or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the informed consent.
2. 2. Capable of giving signed informed consent as described in Section 10.1.3, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
3. 3. Newly diagnosed MM with a requirement for treatment as documented per IMWG criteria. a) Monoclonal plasma cells in the BM ≥10% or presence of a biopsy proven plasmacytoma and documented MM satisfying at least 1 of the CRAB criteria. CRAB criteria: Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than ULN or >2.75 mmol/L (>11 mg/dL); Renal insufficiency: creatinine CL <40 mL/min or serum creatinine >177 μmol/L (>2 mg/dL); Anemia: hemoglobin >2 g/dL below the lower limit of normal or hemoglobin <10 g/dL; Bone lesions: 1 or more osteolytic lesions on skeletal radiography, CT), or PETCT. OR b) Biomarkers of malignancy criteria: Clonal BM plasma cell percentage ≥60%; Involved: uninvolved serum FLC ratio ≥100; >1 focal lesion on MRI studies.
4. 4. Must have at least 1 aspect of measurable disease, as assessed by the central laboratory, defined as 1 of the following: a) Urine M-protein excretion ≥200 mg/24 hours (≥0.2 g/24 hours). And/or b) Serum M-protein concentration ≥0.5 g/dL (≥5.0 g/L) And/or c) Serum FLC assay: involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65).
5. 5. Newly diagnosed and not considered candidate for high dose chemotherapy with ASCT due to any of the following: a) Exclusion from treatment with ASCT due to country- or site-specific age restriction. b) Presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT.
6. 6. ECOG performance status of 0 to 2.
7. 7. Adequate organ system function as defined by the laboratory assessments listed in the protocol inclusion criteria.
8. 8. Male participants: • Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. • Male participants are eligible to participate if they agree to the following during the Treatment Period and for at least 6 months after the last dose of study intervention to allow for clearance of any altered sperm: -Refrain from donating fresh unwashed semen PLUS either: • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent. OR • Must agree to use contraception/barrier as detailed below • Agree to use a male condom, even if they have undergone a successful vasectomy, and female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year when having sexual intercourse with a WOCBP who is not currently pregnant. Male participants should also use a condom when having sexual intercourse with pregnant females.
9. 9. Female participants • Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. • A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: -Is not a WOCBP OR -Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency during the Treatment Period and for 4 months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. -A WOCBP must have 2 negative highly sensitive serum pregnancy tests before starting treatment, the first may be performed within 14 days from C1D1, the second within 24 hours before the first dose of study intervention. -Should pregnancy occur in a female on-treatment or the female partner of a male on-treatment, treatment must be stopped, and it is advised to seek advice from a physician specialized or experienced in teratology.

Exclusion criteria 17

1. 1. Diagnosis of systemic amyloid light chain amyloidosis, Waldenstrom’s disease, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes) or Primary Plasma Cell Leukemia (defined as circulating plasma cells >5%).
2. 2. Prior systemic therapy for MM, or smoldering MM.
3. 3. Signs of meningeal or central nervous system involvement with MM.
4. 4. Major surgery within 2 weeks prior to the first dose of study drugs or has not recovered fully from surgery. Kyphoplasty is not considered major surgery.
5. 5. 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.
6. 6. Current active liver or biliary disease (except for Gilbert's syndrome or asymptomatic gallstones, or otherwise stable chronic liver disease as per the investigator's assessment).
7. 7. Participants with previous or concurrent malignancies other than MM are excluded.
8. 8. Evidence of cardiovascular risk including any of the following: a) Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities including second-degree (Mobitz Type II) or third-degree atrioventricular block. b) Recent history (within 3 months of screening) of MI, acute coronary syndromes (including unstable angina), coronary angioplasty or stenting, or bypass grafting. c) Class III or IV heart failure as defined by the NYHA functional classification system.
9. 9. Known HIV infection, unless the participant can meet all of the following criteria: a) Established ART for at least 4 weeks and HIV viral load <400 copies/mL within Screening Period. b) CD4+ T-cell (CD4+) counts ≥350 cells/μL. c) No history of AIDS-defining opportunistic infections within the last 12 months.
10. 10. Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention unless the participant can meet the following criteria: a) RNA test negative. b) Successful antiviral treatment (usually 8 weeks duration) is required, followed by a negative HCV RNA test after a washout period of at least 4 weeks.
11. 11. Participants with hepatitis B will be excluded unless the following criteria can be met: (i.). HBcAb+, HBsAg- (Screening: HBV DNA undetectable, During Study Intervention: Monitoring per protocol, Antiviral treatment instituted if HBV DNA becomes detectable), (ii.). HBsAg+ at screen or within 3 months prior to first dose (Screening: HBV DNA undetectable, highly effective antiviral treatment started at least 4 weeks prior to first dose of study intervention, baseline imaging per protocol, participants with cirrhosis are excluded; During Study Intervention: Antiviral treatment maintained throughout study intervention, monitoring and management per protocol)
12. 12. Current corneal epithelial disease except for mild punctate keratopathy.
13. 13. Intolerance or contraindications to antiviral prophylaxis.
14. 14. Unable to tolerate antithrombotic prophylaxis.
15. 15. Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, or any of the components of the study intervention.
16. 16. Plasmapheresis within 7 days prior to the first dose of study intervention.
17. 17. Participants must not have received a live or live-attenuated vaccine within 30 days prior to first dose of belantamab mafodotin.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. PFS, defined as the time from the date of randomization to the date of first documented disease progression per IMWG criteria by IRC or death from any cause in the absence of progression, whichever occurs first
2. MRD negative status, defined as achieving MRD negativity at 10-5 sensitivity threshold assessed by NGS at least once during the time of confirmed CR or better response per IMWG criteria by IRC

Secondary endpoints 14

1. PFS2, defined as the time from the date of randomization to the date of documented disease progression following the first subsequent antimyeloma therapy or death from any cause, whichever is earlier
2. OS, defined as the time from the date of randomization until the date of death due to any cause
3. CR+, defined as confirmed CR or sCR per IMWG criteria by IRC
4. VGPR+, defined as confirmed VGPR, CR, sCR per IMWG criteria by IRC
5. sMRD, defined as achieving MRD negative status at 10-5 sensitivity threshold assessed by NGS at least twice, a minimum of 1 year apart and with no MRD positive result in between, during the time of confirmed CR or better response per IMWG criteria by IRC
6. DoR, defined as the time from first documented evidence of PR or better until PD or death due to PD (among participants who achieve confirmed PR+ by IRC)
7. TTST, defined as time from randomization until the date of start of second subsequent line of antimyeloma therapy (irrespective of PD) or death due to any cause, whichever is earlier
8. Incidence and severity of AEs and SAEs
9. Incidence of AEs leading to dose modifications or study intervention discontinuation
10. Incidence and severity of ocular findings on ophthalmic exam (changes in VA and corneal findings)
11. Maximum post-baseline PRO-CTCAE score for each item attribute
12. Change from baseline in HRQoL as measured by EORTC QLQ-C30.
13. Change from baseline in HRQoL as measured by EORTC QLQ-MY20 (Disease Symptoms domain)
14. Plasma concentrations of belantamab mafodotin

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Auxiliary 10

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

G S K House, 980 Great West Road 980 Great West Road

City

Brentford

Postcode

TW8 9GS

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 12

Locations

11 EU/EEA countries · 62 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 281 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications