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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04126200




Registration number
NCT04126200
Ethics application status
Date submitted
11/10/2019
Date registered
15/10/2019
Date last updated
20/07/2021

Titles & IDs
Public title
Platform Study of Belantamab Mafodotin as Monotherapy and in Combination With Anti-cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) (DREAMM 5)
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) - DREAMM 5
Secondary ID [1] 0 0
208887
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
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Belantamab mafodotin
Treatment: Drugs - GSK3174998
Treatment: Drugs - Feladilimab
Treatment: Drugs - Nirogacestat
Treatment: Drugs - Dostarlimab
Treatment: Drugs - Isatuximab

Experimental: Belantamab mafodotin+GSK3174998 dose exploration (Sub-study 1) -

Experimental: Belantamab mafodotin+feladilimab dose exploration (Sub-study 2) -

Experimental: Belantamab mafodotin+nirogacestat dose exploration(Sub-study 3) -

Experimental: Belantamab mafodotin+dostarlimab dose exploration(Sub-study 4) -

Experimental: Belantamab mafodotin+isatuximab dose exploration (Sub-study 5) -

Active Comparator: Belantamab mafodotin monotherapy cohort expansion -

Experimental: Belantamab mafodotin+GSK3174998 cohort expansion (Sub-study 1) -

Experimental: Belantamab mafodotin+ feladilimab cohort expansion (Sub-study 2) -

Experimental: Belantamab mafodotin+ nirogacestat cohort expansion(Sub-study 3) -

Experimental: Belantamab mafodotin+ dostarlimab cohort expansion(Sub-study 4) -

Experimental: Belantamab mafodotin+ isatuximab cohort expansion(Sub-study 5) -


Treatment: Drugs: Belantamab mafodotin
Belantamab mafodotin will be administered

Treatment: Drugs: GSK3174998
GSK3174998 will be administered

Treatment: Drugs: Feladilimab
feladilimab will be administered.

Treatment: Drugs: Nirogacestat
Nirogacestat will be administered

Treatment: Drugs: Dostarlimab
Dostarlimab will be administered.

Treatment: Drugs: Isatuximab
Isatuximab will be administered

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
DE Phase: Number of participants achieving dose limiting toxicities (DLT) - An event is considered to be a dose DLT if the event occurs within the first 21 days of treatment and meets the dose limiting toxicity criteria.
Timepoint [1] 0 0
Up to 36 months
Primary outcome [2] 0 0
DE Phase: Number of participants with adverse events (AEs) and serious adverse events (SAEs) - AEs and SAEs will be collected.
Timepoint [2] 0 0
Up to 36 months
Primary outcome [3] 0 0
DE Phase: Number of participants with abnormality in vital signs - Vital sign measurements will include systolic and diastolic blood pressure, temperature, respiratory rate and pulse rate.
Timepoint [3] 0 0
Up to 36 months
Primary outcome [4] 0 0
DE Phase: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters - Blood and urine samples will be collected to evaluate hematology, clinical chemistry and urinalysis lab parameters.
Timepoint [4] 0 0
Up to 36 months
Primary outcome [5] 0 0
CE Phase: Number of participants achieving Overall Response Rate (ORR) - ORR is defined as the percentage of participants with a Partial response (PR) or better, according to the International Myeloma Working Group (IMWG) Response Criteria.
Timepoint [5] 0 0
Up to 36 months
Secondary outcome [1] 0 0
DE Phase: Number of participants achieving ORR - ORR is defined as the percentage of participants with PR or better, according to the IMWG Response Criteria.
Timepoint [1] 0 0
Up to 36 months
Secondary outcome [2] 0 0
CE Phase: Number of participants achieving Clinical Benefit Rate (CBR) - CBR is defined as the percentage of participants with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to a therapeutic intervention in clinical trials of anticancer agents.
Timepoint [2] 0 0
Up to 36 months
Secondary outcome [3] 0 0
DE Phase and CE Phase: Number of participants achieving Partial Response - Number of participants with PR according to IMWG criteria will be analyzed.
Timepoint [3] 0 0
Up to 36 months
Secondary outcome [4] 0 0
DE Phase and CE Phase: Number of participants achieving Very Good Partial Response (VGPR) - Number of participants with VGPR according to IMWG criteria will be analyzed.
Timepoint [4] 0 0
Up to 36 months
Secondary outcome [5] 0 0
DE Phase and CE Phase: Number of participants achieving Complete Response (CR) - Participants with CR according to IMWG criteria will be analyzed.
Timepoint [5] 0 0
Up to 36 months
Secondary outcome [6] 0 0
DE Phase and CE Phase: Number of participants achieving stringent Complete Response (sCR) - Participants with sCR according to IMWG criteria will be analyzed.
Timepoint [6] 0 0
Up to 36 months
Secondary outcome [7] 0 0
DE Phase and CE Phase: Belantamab mafodotin concentrations when administered in combination with anti-cancer treatments - Blood samples will be collected for concentrations of belantamab mafodotin.
Timepoint [7] 0 0
Up to 36 months
Secondary outcome [8] 0 0
DE Phase and CE Phase: GSK3174998 concentration when administered in combination with belantamab mafodotin - Blood samples will be collected for concentrations of GSK3174998.
Timepoint [8] 0 0
Up to 36 months
Secondary outcome [9] 0 0
DE Phase and CE Phase: feladilimab concentration when administered in combination with belantamab mafodotin - Blood samples will be collected for concentrations of feladilimab.
Timepoint [9] 0 0
Up to 36 months
Secondary outcome [10] 0 0
DE Phase and CE Phase: Nirogacestat concentration when administered in combination with belantamab mafodotin - Blood samples will be collected for concentrations of nirogacestat.
Timepoint [10] 0 0
Up to 36 months
Secondary outcome [11] 0 0
DE Phase and CE Phase: Dostarlimab concentration when administered in combination with belantamab mafodotin - Blood samples will be collected for concentrations of dostarlimab.
Timepoint [11] 0 0
Up to 36 months
Secondary outcome [12] 0 0
DE Phase and CE Phase: Isatuximab concentration when administered in combination with belantamab mafodotin - Blood samples will be collected for concentrations of isatuximab.
Timepoint [12] 0 0
Up to 36 months
Secondary outcome [13] 0 0
DE Phase and CE Phase: Concentration of anti-drug antibodies (ADAs) against belantamab mafodotin when administered in combination with anti-cancer treatments - Blood samples for concentrations for ADAs will be collected.
Timepoint [13] 0 0
Up to 36 months
Secondary outcome [14] 0 0
DE Phase and CE Phase: Concentration of ADAs against GSK3174998 when administered in combination with belantamab mafodotin - Blood samples for concentrations for ADAs will be collected.
Timepoint [14] 0 0
Up to 36 months
Secondary outcome [15] 0 0
DE Phase and CE Phase: Concentration of ADAs against feladilimab when administered in combination with belantamab mafodotin - Blood samples for concentrations for ADAs will be collected.
Timepoint [15] 0 0
Up to 36 months
Secondary outcome [16] 0 0
DE Phase and CE Phase: Concentration of ADAs against dostarlimab when administered in combination with belantamab mafodotin - Blood samples for concentrations for ADAs will be collected.
Timepoint [16] 0 0
Up to 36 months
Secondary outcome [17] 0 0
DE Phase and CE Phase: Concentration of ADAs against isatuximab when administered in combination with belantamab mafodotin - Blood samples for concentrations for ADAs will be collected.
Timepoint [17] 0 0
Up to 36 months
Secondary outcome [18] 0 0
DE Phase and CE Phase: Number of participants with adverse events of special interest (AESI) - AESIs will be collected.
Timepoint [18] 0 0
Up to 36 months
Secondary outcome [19] 0 0
DE Phase and CE Phase: Number of participants with abnormal ocular findings on ophthalmic examination - Ophthalmic examination will assess abnormal findings.
Timepoint [19] 0 0
Up to 36 months
Secondary outcome [20] 0 0
CE Phase: Number of participants achieving Progression-free survival (PFS) - PFS is defined as the time from randomization until the earliest date of confirmed progressive disease (PD) per IMWG, or death due to any cause.
Timepoint [20] 0 0
Up to 36 months
Secondary outcome [21] 0 0
CE Phase: Duration of response (DoR) - DoR is defined as the time from first documented evidence or PR or better until progressive disease per IMWG or death due to progressive disease among participants who achieve confirmed partial response or better.
Timepoint [21] 0 0
Up to 36 months
Secondary outcome [22] 0 0
CE Phase: Time to response (TTR) - TTR is 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 (confirmed PR or better).
Timepoint [22] 0 0
Up to 36 months
Secondary outcome [23] 0 0
CE Phase: Number of participants achieving Overall survival (OS) - OS is defined as the time from randomization until death due to any cause.
Timepoint [23] 0 0
Up to 36 months
Secondary outcome [24] 0 0
CE Phase: Number of participants with AEs and SAEs - AEs and SAEs will be collected.
Timepoint [24] 0 0
Up to 36 months
Secondary outcome [25] 0 0
CE Phase: Number of participants with AEs leading to discontinuation - Number of participants with AEs leading to discontinuation will be evaluated.
Timepoint [25] 0 0
Up to 36 months
Secondary outcome [26] 0 0
CE Phase: Number of participants with dose reduction or delay - Number of participants with dose reduction or delay will be evaluated.
Timepoint [26] 0 0
Up to 36 months
Secondary outcome [27] 0 0
CE Phase: Number of participants with abnormality in vital signs - Vital sign measurements will include systolic and diastolic blood pressure, temperature, respiratory rate and pulse rate.
Timepoint [27] 0 0
Up to 36 months
Secondary outcome [28] 0 0
CE Phase: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters - Blood and urine samples will be collected to evaluate hematology, clinical chemistry and urinalysis lab parameters.
Timepoint [28] 0 0
Up to 36 months

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 immunodilating 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 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).
Minimum age
18 Years
Maximum age
No limit
Gender
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.

Additional Exclusion Criteria for Sub-study 1 and Sub-study 2:

- Participants with autoimmune disease (current or history) or syndrome that required
systemic treatment within the past 2 years.

- Exclusion for a recent (within the past 6 months) history of symptomatic pericarditis.

Additional Exclusion Criteria for Sub-study 3:

- 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 or moderate CYP3A4 inhibitor
or inducer.

Additional Exclusion Criteria for Sub-study 4:

- Participant has an active autoimmune disease that has required systemic treatment in
the past 2 years (i.e. with use of disease-modifying agents, corticosteroids, or
immunosuppressive drugs).

- Participants who have received prior therapy with an anti-programmed death-1
(anti-PD-1), anti-PD-1-ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD-L2)
agent.

- Participant has a diagnosis of immunodeficiency or is receiving systemic steroid
therapy or any other form of immunosuppressive therapy within 7 days prior to the
first dose of study treatment. Use of inhaled steroids, local injection of steroids,
and steroid eye drops are allowed.

Additional Exclusion Criteria for Sub-study 5:

- Participants with Severe hypersensitivity to Isatuximab-irfc or to any of its
excipients.

- Participants with prior treatment with other anti-CD38 monoclonal antibody within 6
months of the first dose of study drug treatment.

- Participants with known intolerance or hypersensitivity to infused proteins products,
sucrose, histidine, and polysorbate 80.

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/Phase 2
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Fitzroy
Recruitment hospital [2] 0 0
GSK Investigational Site - Melbourne
Recruitment postcode(s) [1] 0 0
3065 - Fitzroy
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
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
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
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
Ontario
Country [7] 0 0
France
State/province [7] 0 0
Lille Cedex
Country [8] 0 0
France
State/province [8] 0 0
Villejuif Cedex
Country [9] 0 0
Germany
State/province [9] 0 0
Hamburg
Country [10] 0 0
Korea, Republic of
State/province [10] 0 0
Seoul
Country [11] 0 0
Korea, Republic of
State/province [11] 0 0
Ulsan
Country [12] 0 0
Netherlands
State/province [12] 0 0
Amsterdam
Country [13] 0 0
Netherlands
State/province [13] 0 0
Utrecht
Country [14] 0 0
Spain
State/province [14] 0 0
Madrid
Country [15] 0 0
Spain
State/province [15] 0 0
Pamplona
Country [16] 0 0
Sweden
State/province [16] 0 0
Stockholm

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

Ethics approval
Ethics application status

Summary
Brief summary
B-cell maturation antigen (BCMA) is a target present on tumor cells in participants with
multiple myeloma. Belantamab mafodotin (GSK2857916); is an antibody-drug conjugate (ADC)
containing humanized anti-BCMA monoclonal antibody (mAb). This is a phase I/II, randomized,
open-label, platform study designed to evaluate the effects of belantamab mafodotin in
combination with other anti-cancer drugs in participants with relapsed/refractory multiple
myeloma. The Platform design incorporates a single master protocol, where multiple treatment
combinations, as sub-studies, will be evaluated simultaneously.
Trial website
https://clinicaltrials.gov/show/NCT04126200
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US GSK Clinical Trials Call Center
Address 0 0
Country 0 0
Phone 0 0
877-379-3718
Fax 0 0
Email 0 0
GSKClinicalSupportHD@gsk.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04126200