This study will evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of belantamab mafodotin in combination with Velcade (bortezomib), Revlimid (lenalidomide), dexamethasone (VRd) and will determine recommended phase 3 dose (RP3D) in adult participants with newly diagnosed multiple myeloma (NDMM). Participants will receive the combination of bortezomib, lenalidomide and dexamethasone (VRd) on a 3-week cycle until cycle 8, followed by the combination of lenalidomide and dexamethasone (Rd) on a 4-week cycle thereafter as per dosing schedule. Participants will receive belantamab mafodotin on a schedule that is dependent on the cohort to which they are assigned. Belantamab mafodotin will be administered in combination with VRd every 3 weeks (Q3W), every 6 weeks (Q6W), or every 9 weeks (Q9W) to Cycle 8, and then in combination with Rd every 4 weeks (Q4W), every 8 weeks (Q8W), or every 12 weeks (Q12W) thereafter. Participants will complete an End of Treatment (EOT) visit at the point of study treatment discontinuation, followed by a Safety Follow-up visit 70 days after EOT.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
118
Selected doses of belantamab mafodotin will be administered as intravenous infusion.
Bortezomib will be administered subcutaneously or intravenously approximately 1 hour after the belantamab mafodotin infusion until Cycle 8.
Lenalidomide will be administered as 25 or 10 mg orally, depending upon renal function.
Dexamethasone will be administered orally as 20 mg in cycles 1-8 and 40 mg in Cycle 9 onwards.
GSK Investigational Site
Westwood, Kansas, United States
GSK Investigational Site
Charlotte, North Carolina, United States
GSK Investigational Site
Madison, Wisconsin, United States
GSK Investigational Site
Newcastle, New South Wales, Australia
GSK Investigational Site
Clayton, Victoria, Australia
GSK Investigational Site
Fitzroy, Victoria, Australia
GSK Investigational Site
Edmonton, Alberta, Canada
GSK Investigational Site
London, Ontario, Canada
GSK Investigational Site
Poitiers, France
GSK Investigational Site
Dresden, Germany
...and 20 more locations
Number of participants with dose-limiting toxicities (DLTs)
The number of participants with DLTs will be reported.
Time frame: Treatment cycle 1 to 3 (each cycle of 21 days)
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
AEs and SAEs will be collected.
Time frame: Up to an average of 54 months
Lenalidomide relative dose intensity (RDI ) of treatment with belantamab mafodotin in combination with VRd
RDI of treatment with belantamab mafodotin in combination with VRd will be analyzed.
Time frame: 4 treatment cycles (each cycle of 21 days)
Bortezomib RDI of treatment with belantamab mafodotin in combination with VRd
RDI of treatment with belantamab mafodotin in combination with VRd will be analyzed.
Time frame: 4 treatment cycles (each cycle of 21 days)
Cumulative administered dose of belantamab mafodotin treatment in combination with VRd
Cumulative administered dose of belantamab mafodotin in treatment in combination with VRd will be analyzed.
Time frame: 4 treatment cycles (each cycle of 21 days)
Maximum plasma concentration (Cmax) of belantamab mafodotin
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to an average of 52 months
Cmax of microtubule inhibitor monomethyl auristatin-F with a cysteine linker (cys-mcMMAF)
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to an average of 52 months
Area under the concentration time curve (AUC) of belantamab mafodotin
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to an average of 52 months
AUC of cys-mcMMAF
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to an average of 52 months
Number of participants with positive anti-drug antibodies (ADAs) against belantamab mafodotin
Serum samples for the analysis of anti-belantamab mafodotin antibodies will be collected. The samples will be tested for anti-belantamab mafodotin antibodies using a tiered-testing scheme consisting of validated screening, confirmation, and titration assays.
Time frame: Up to an average of 52 months
Titers of ADAs against belantamab mafodotin
Serum samples for the analysis of anti-belantamab mafodotin antibodies will be collected. The samples will be tested for anti-belantamab mafodotin antibodies using a tiered-testing scheme consisting of validated screening, confirmation, and titration assays.
Time frame: Up to an average of 52 months
Overall Response Rate (ORR)
ORR is defined as the percentage of participants with a confirmed partial response (PR) or better based on the response assessed by the investigator using International Myeloma Working Group (IMWG) criteria.
Time frame: Up to 52 months
Complete Response Rate (CRR)
CRR is defined as the percentage of participants with a confirmed complete response (CR) or better based on the response assessed by the investigator using IMWG criteria.
Time frame: Up to 52 months
Rate of Very Good Partial Response (VGPR) or better
Rate of VGPR or better is defined as the percentage of participants with a confirmed VGPR or better based on the response assessed by the investigator using IMWG criteria.
Time frame: Up to 52 months
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