Primary Objectives: * To evaluate the safety and tolerability of isatuximab administered subcutaneously (SC) versus intravenously (IV) * To assess the safety and tolerability (including local injection site tolerability) of isatuximab using the (investigational) isatuximab injector device * To evaluate the pharmacokinetics (PK) of SC and IV isatuximab Secondary Objectives: * To estimate absolute bioavailability of SC and IV isatuximab * To measure receptor occupancy (RO) after isatuximab SC versus IV administration * To assess efficacy of isatuximab after SC and IV administration * To assess patient expectations prior to and patient experience and satisfaction after SC administration * To evaluate potential immunogenicity of SC or IV isatuximab
Total study duration is variable depending on treatment and follow-up periods, including 21 days of screening, and treatment period until disease progression, unacceptable adverse reaction or other reason for discontinuation. End of treatment will be 30 days after last administration of investigational medicinal product, or before further anti-myeloma therapy, whichever comes first; approximately 14 months after first study treatment administration.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
56
Pharmaceutical form: solution Route of administration: intravenous
Pharmaceutical form: tablet Route of administration: oral
Pharmaceutical form: tablet Route of administration: oral
Pharmaceutical form: solution Route of administration: subcutaneous
Subcutaneous administration
~Banner MD Anderson Cancer Center Site Number : 8400005
Gilbert, Arizona, United States
City of Hope Site Number : 8400002
Duarte, California, United States
Gabrail Cancer Center Site Number : 8400001
Canton, Ohio, United States
Investigational Site Number : 0360002
Blacktown, New South Wales, Australia
Investigational Site Number : 0360001
Wollongong, New South Wales, Australia
Investigational Site Number : 0360004
Fitzroy, Victoria, Australia
Investigational Site Number : 0360003
Richmond, Victoria, Australia
Investigational Site Number : 0560001
Leuven, Belgium
Investigational Site Number : 2500001
Nantes, France
Investigational Site Number : 2500002
Toulouse, France
...and 4 more locations
Assessment of adverse events (AEs)
Number of participants with adverse events
Time frame: Baseline to 30 days after last study treatment administration (up to approximately 14 months after first study treatment administration)
Pharmacokinetic (PK) assessment: Ceoi
Concentration observed at the end of infusion (Ceoi)
Time frame: Baseline to end of treatment (EOT) after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
PK assessment: Cmax
Maximum concentration observed after the first infusion (Cmax)
Time frame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
PK assessment: tmax
Time to reach Cmax (tmax)
Time frame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
PK assessment: Clast
Last concentration observed above the lower limit of quantification after the first infusion (Clast)
Time frame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
PK assessment: tlast
Time of Clast (tlast)
Time frame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
PK assessment: Ctrough
Concentration observed just before treatment administration during repeated dosing (Ctrough)
Time frame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
PK assessment: AUClast
Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to time of the last concentration observed above the lower limit of quantification (ie, Clast) (AUClast)
Time frame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
PK assessment: AUC0 T
Area under the plasma concentration versus time curve calculated over the dosing interval T (168h or 336h) (AUC0 T)
Time frame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Estimation of absolute bioavailability of isatuximab
Absolute bioavailability of isatuximab SC, expressed as a percentage, estimated from AUC0-168h obtained after intravenous (IV) and extravascular (EV) administration
Time frame: Day 8
Overall response rate (ORR)
ORR is the proportion of patients with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) using the IMWG response criteria
Time frame: From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Duration of response (DOR)
Time from the date of the first response to the date of first progressive disease (PD) or death, whichever happens first
Time frame: From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Time to response (TTR)
Time from the date of first study treatment to the first response
Time frame: From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Time to progression (TTP)
Time from date of first study treatment to date of first documentation of progressive disease
Time frame: From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Overall survival (OS)
Time from the date of first study treatment to date of death from any cause
Time frame: From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Clinical benefit rate (CBR)
Proportion of patients with sCR, CR, VGPR, PR or minimal response (MR) according to IMWG criteria
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Time frame: From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Progression free survival (PFS)
Time from date of first study treatment to date of first documentation of progressive disease or death
Time frame: From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Comparison of patient expectations and satisfaction: Patient Expectations and Satisfaction Questionnaires
Comparison of patient expectations and satisfaction will be assessed using Patient Expectations and Satisfaction Questionnaires before and after subcutaneous (SC) administration, where a score of 1 = not satisfied and a score of 5 = extremely satisfied
Time frame: Cycles 1 and 2 (28 days per Cycle), and 30 days after last isatuximab administration (up to approximately 14 months after first study treatment administration)
Immunogenicity: Anti drug antibody levels
Incidence of patients with anti drug antibodies against isatuximab
Time frame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Biomarker: Change in CD38 receptor occupancy
Change in CD38 receptor occupancy from baseline
Time frame: At screening and at Day 1 of Cycle 2 (28 days per Cycle) (predose); to be stopped once the isatuximab SC dose has been selected.