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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT07084896




Registration number
NCT07084896
Ethics application status
Date submitted
22/07/2025
Date registered
25/07/2025
Date last updated
25/07/2025

Titles & IDs
Public title
Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With Nirogacestat in Participants With RRMM
Scientific title
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)-DREAMM5 - Sub-study 3 - Belantamab Mafodotin and Nirogacestat in Combination
Secondary ID [1] 0 0
2023-509550-55
Secondary ID [2] 0 0
208887 Sub Study 3
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Belantamab mafodotin
Treatment: Drugs - Nirogacestat

Experimental: Belantamab mafodotin + Nirogacestat -


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

Treatment: Drugs: Nirogacestat
Nirogacestat will be administered.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose Exploration (DE) Phase: Number of participants with dose limiting toxicities (DLTs)
Timepoint [1] 0 0
Up to 21 days
Primary outcome [2] 0 0
DE Phase: Number of participants with adverse events (AEs)
Timepoint [2] 0 0
Up to approximately 253 weeks
Primary outcome [3] 0 0
DE Phase: Number of participants with clinically significant changes in hematology, clinical chemistry, and urinalysis lab parameters
Timepoint [3] 0 0
Up to approximately 253 weeks
Primary outcome [4] 0 0
Cohort Expansion (CE) Phase: Overall Response Rate (ORR)
Timepoint [4] 0 0
Up to approximately 253 weeks
Secondary outcome [1] 0 0
DE Phase: Overall Response Rate
Timepoint [1] 0 0
Up to approximately 253 weeks
Secondary outcome [2] 0 0
CE Phase: Clinical Benefit Rate (CBR)
Timepoint [2] 0 0
Up to approximately 253 weeks
Secondary outcome [3] 0 0
DE Phase: Number of participants achieving Partial Response (PR)
Timepoint [3] 0 0
Up to approximately 253 weeks
Secondary outcome [4] 0 0
CE Phase: Number of participants achieving PR
Timepoint [4] 0 0
Up to approximately 253 weeks
Secondary outcome [5] 0 0
DE Phase: Number of participants achieving Very Good Partial Response (VGPR)
Timepoint [5] 0 0
Up to approximately 253 weeks
Secondary outcome [6] 0 0
CE Phase: Number of participants achieving VGPR
Timepoint [6] 0 0
Up to approximately 253 weeks
Secondary outcome [7] 0 0
DE Phase: Number of participants achieving Complete Response (CR)
Timepoint [7] 0 0
Up to approximately 253 weeks
Secondary outcome [8] 0 0
CE Phase: Number of participants achieving CR
Timepoint [8] 0 0
Up to approximately 253 weeks
Secondary outcome [9] 0 0
DE Phase: Number of participants achieving Stringent Complete Response (sCR)
Timepoint [9] 0 0
Up to approximately 253 weeks
Secondary outcome [10] 0 0
CE Phase: Number of participants achieving sCR
Timepoint [10] 0 0
Up to approximately 253 weeks
Secondary outcome [11] 0 0
DE Phase: Belantamab mafodotin concentrations when administered in combination with anti-cancer treatments
Timepoint [11] 0 0
Up to approximately 253 weeks
Secondary outcome [12] 0 0
CE Phase: Belantamab mafodotin concentrations when administered in combination with anti-cancer treatments
Timepoint [12] 0 0
Up to approximately 253 weeks
Secondary outcome [13] 0 0
DE Phase: Nirogacestat concentration when administered in combination with belantamab mafodotin
Timepoint [13] 0 0
Up to approximately 253 weeks
Secondary outcome [14] 0 0
CE Phase: Nirogacestat concentration when administered in combination with belantamab mafodotin
Timepoint [14] 0 0
Up to approximately 253 weeks
Secondary outcome [15] 0 0
DE Phase: Number of participants with anti-drug antibodies (ADAs) against belantamab mafodotin
Timepoint [15] 0 0
Up to approximately 253 weeks
Secondary outcome [16] 0 0
DE Phase: Titre of (ADAs) against belantamab mafodotin
Timepoint [16] 0 0
Up to approximately 253 weeks
Secondary outcome [17] 0 0
CE Phase: Number of participants with ADAs against belantamab mafodotin
Timepoint [17] 0 0
Up to approximately 253 weeks
Secondary outcome [18] 0 0
CE Phase: Titre of ADAs against belantamab mafodotin
Timepoint [18] 0 0
Up to approximately 253 weeks
Secondary outcome [19] 0 0
DE Phase: Number of participants with adverse events of special interest (AESI) for belantamab mafodotin
Timepoint [19] 0 0
Up to approximately 253 weeks
Secondary outcome [20] 0 0
CE Phase: Number of participants with AESI for belantamab mafodotin
Timepoint [20] 0 0
Up to approximately 253 weeks
Secondary outcome [21] 0 0
DE Phase: Number of participants with AESI for Nirogacestat
Timepoint [21] 0 0
Up to approximately 253 weeks
Secondary outcome [22] 0 0
CE Phase: Number of participants with AESI for Nirogacestat
Timepoint [22] 0 0
Up to approximately 253 weeks
Secondary outcome [23] 0 0
DE Phase: Number of participants with abnormal ocular findings on ophthalmic examination
Timepoint [23] 0 0
Up to approximately 253 weeks
Secondary outcome [24] 0 0
CE Phase: Number of participants with abnormal ocular findings on ophthalmic examination
Timepoint [24] 0 0
Up to approximately 253 weeks
Secondary outcome [25] 0 0
CE Phase: Progression-free survival (PFS)
Timepoint [25] 0 0
Up to approximately 253 weeks
Secondary outcome [26] 0 0
CE Phase: Duration of response (DoR)
Timepoint [26] 0 0
Up to approximately 253 weeks
Secondary outcome [27] 0 0
CE Phase: Time to response (TTR)
Timepoint [27] 0 0
Up to approximately 253 weeks
Secondary outcome [28] 0 0
CE Phase: Overall survival (OS)
Timepoint [28] 0 0
Up to approximately 253 weeks
Secondary outcome [29] 0 0
CE Phase: Number of participants with AEs and SAEs
Timepoint [29] 0 0
Up to approximately 253 weeks
Secondary outcome [30] 0 0
CE Phase: Number of participants with AEs leading to discontinuation
Timepoint [30] 0 0
Up to approximately 253 weeks
Secondary outcome [31] 0 0
CE Phase: Number of participants with dose reduction or delay
Timepoint [31] 0 0
Up to approximately 253 weeks
Secondary outcome [32] 0 0
CE Phase: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters
Timepoint [32] 0 0
Up to approximately 253 weeks

Eligibility
Key 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 ophthalmological steroids.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.
* Participants with uncontrolled small and/or large intestinal disease.
* Participants with uncontrolled skin disease.
* Participants with any condition causing hypophosphatemia, hypokalemia or hypomagnesemia which is refractory to electrolyte replacement.
* Participants with previous administration of a gamma secretase inhibitor.
* Participants with concomitant administration of a strong CYP3A4 inhibitor or inducer.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/06/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
11/03/2027
Actual
Sample size
Target
Accrual to date
Final
106
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Fitzroy
Recruitment postcode(s) [1] 0 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Georgia
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
Wisconsin
Country [5] 0 0
Canada
State/province [5] 0 0
British Columbia
Country [6] 0 0
Canada
State/province [6] 0 0
Nova Scotia
Country [7] 0 0
France
State/province [7] 0 0
Lille
Country [8] 0 0
France
State/province [8] 0 0
Villejuif
Country [9] 0 0
Germany
State/province [9] 0 0
Frankfurt
Country [10] 0 0
Germany
State/province [10] 0 0
Kiel
Country [11] 0 0
Germany
State/province [11] 0 0
Leipzig
Country [12] 0 0
Greece
State/province [12] 0 0
Athens
Country [13] 0 0
Netherlands
State/province [13] 0 0
Utrecht
Country [14] 0 0
Norway
State/province [14] 0 0
Oslo
Country [15] 0 0
Poland
State/province [15] 0 0
Katowice
Country [16] 0 0
Poland
State/province [16] 0 0
Lodz
Country [17] 0 0
Poland
State/province [17] 0 0
Lublin
Country [18] 0 0
Russia
State/province [18] 0 0
Moscow
Country [19] 0 0
South Korea
State/province [19] 0 0
Incheon
Country [20] 0 0
South Korea
State/province [20] 0 0
Seoul
Country [21] 0 0
South Korea
State/province [21] 0 0
Ulsan
Country [22] 0 0
Spain
State/province [22] 0 0
Badalona
Country [23] 0 0
Spain
State/province [23] 0 0
Madrid
Country [24] 0 0
Spain
State/province [24] 0 0
Pozuelo de AlarcOn Madr
Country [25] 0 0
Sweden
State/province [25] 0 0
Falun
Country [26] 0 0
Sweden
State/province [26] 0 0
Stockholm

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
GSK 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.


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT07084896