This is a Phase II, open-label, nonrandomized, single-arm study of elranatamab that will be administered in the outpatient setting in 2 sequential cohorts of participants with relapsed or refractory multiple myeloma (RRMM). The primary objective of this study is to evaluate the overall incidence of cytokine release syndrome (CRS) during Cycle 1 of elranatamab treatment following a single prophylactic dose of tocilizumab.
This is a Phase II, open-label, nonrandomized, single-arm study of elranatamab that will be administered in the outpatient setting in 2 sequential cohorts of participants with relapsed or refractory multiple myeloma (RRMM) who have received ≥1 prior line of therapy and are double class exposed (lenalidomide and an anti-CD38). A safety-lead in will be employed for the first 6 evaluable participants (participants who have completed Cycle 1) (Cohort 1), followed by an expansion cohort (Cohort 2) of 40 participants. Eligible participants will receive a single prophylactic dose of tocilizumab followed by treatment with elranatamab. Tocilizumab, an interleukin-6 (IL-6) receptor antagonist, is approved for the treatment of Chimeric Antigen Receptor T-Cell (CAR-T)-associated CRS, and has shown promise in reducing CRS incidence when used prophylactically in bispecific antibody trials. Elranatamab is a bispecific antibody targeting B-cell maturation antigen (BCMA) and CD3, designed to redirect T cells to eliminate malignant plasma cells in multiple myeloma (MM).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
46
Elranatamab will be administered subcutaneously (SC) in step-up doses on Day 1 (12 mg) and Day 4 (32 mg) followed by dosing of 76 mg on Day 8, Day 15, and Day 22 during Cycle 1, then 76 mg every other week for Cycle 2 and 3. For Cycles 4- 12, elranatamab 76 mg dose will be given once a cycle. Participants will receive a maximum of 12 cycles of elranatamab. Cycles will be 28 days.
A single (one time) intravenous (IV) dose of tocilizumab 8 mg/kg will be administered 1-4 hours prior to the first step-up dose (SUD) of elranatamab in Cycle 1. Cycles will be 28 days.
Incidence of Cytokine Release Syndrome (CRS) in Cycle 1
Evaluate the number of participants with events of CRS during Cycle 1 of study treatment. CRS events will be graded per the American Society for Transplantation and Cellular Therapy grading (ASTCT 2019).
Time frame: From Cycle 1 Day 1 to Cycle 1 Day 28 for all participants. Each cycle is 28 days.
Incidence of ≥ Grade 2 CRS during Cycle 1
Evaluate the number of participants with Grade 2 or greater events of CRS during Cycle 1 of study treatment. CRS events will be graded per the American Society for Transplantation and Cellular Therapy grading (ASTCT 2019).
Time frame: From Cycle 1 Day 1 to Cycle 1 Day 28 for all participants. Each cycle is 28 days.
Incidence of all-grade CRS
Evaluate the number of participants with any grade of events of CRS during any time on study treatment. CRS events will be graded per the American Society for Transplantation and Cellular Therapy grading (ASTCT 2019).
Time frame: Every cycle from Cycle 1 Day 1 to 30 days after last dose of elranatamab, up to approximately 13 months (12 cycles, 28-day cycle length plus 30 days of follow-up).
Incidence of recurrent CRS
Evaluate the number of participants with multiple events of CRS during any time on study treatment. CRS events will be graded per the American Society for Transplantation and Cellular Therapy grading (ASTCT 2019).
Time frame: Every cycle from Cycle 1 Day 1 to 30 days after last dose of elranatamab, up to approximately 13 months (12 cycles, 28-day cycle length plus 30 days of follow-up).
Timing of CRS relative to the first dose of elranatamab
Evaluate the the frequency of any events of CRS occurring at different intervals of time following administration of the first dose of elranatamab. CRS events will be graded per the American Society for Transplantation and Cellular Therapy grading (ASTCT 2019).
Time frame: From Cycle 1 Day 1 to 30 days after last dose of elranatamab, up to approximately 13 months (12 cycles, 28-day cycle length plus 30 days of follow-up).
Incidence of ≥ Grade 3 infections
Evaluate the number of participants with Grade 3 or greater infections during any time on study treatment. All infections will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 6.0.
Time frame: Every cycle from Cycle 1 Day 1 to 30 days after last dose of elranatamab, up to approximately 13 months (12 cycles, 28-day cycle length plus 30 days of follow-up).
Incidence of all-grade infections
Evaluate the number of participants with any grade of infections during any time on study treatment. All infections will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 6.0.
Time frame: Every cycle from Cycle 1 Day 1 to 30 days after last dose of elranatamab, up to approximately 13 months (12 cycles, 28-day cycle length plus 30 days of follow-up).
Incidence of neurotoxicity (Immune effector cell-associated neurotoxicity syndrome)
Evaluate the number of participants with any grade of events of Immune effector cell-associated neurotoxicity syndrome (ICANS) during any time on study treatment. ICANS events will be graded per the American Society for Transplantation and Cellular Therapy grading (ASTCT 2019).
Time frame: Every cycle from Cycle 1 Day 1 to 30 days after last dose of elranatamab, up to approximately 13 months (12 cycles, 28-day cycle length plus 30 days of follow-up).
Time to resolution of CRS
The median time from the date of the first dose of elranatamab to the date of first documented resolution of CRS for all participants who experienced CRS.
Time frame: From Cycle 1 Day 1 to 30 days after last dose of elranatamab, up to approximately 13 months (12 cycles, 28-day cycle length plus 30 days of follow-up).
Time to resolution of ICANS
The median time from the date of the first dose of elranatamab to the date of first documented resolution of ICANS for all participants who experienced ICANS.
Time frame: From Cycle 1 Day 1 to 30 days after last dose of elranatamab, up to approximately 13 months (12 cycles, 28-day cycle length plus 30 days of follow-up).
Overall response rate
Overall response rate (ORR) will be defined as the percentage of participants who achieve a PR or better response according to the International Myeloma Working Group (IMWG) 2016 response criteria.
Time frame: Every cycle from Cycle 1 Day 1 to end of Cycle 12 (end of study treatment), up to approximately 12 months (12 cycles, 28-day cycle length).
Duration of response
Duration of response (DOR) will be calculated among responders only (i.e. participants who achieve a PR or better response according to the International Myeloma Working Group (IMWG) 2016 response criteria). DOR is defined as the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG response criteria.
Time frame: Every cycle from Cycle 1 Day 1 to end of Cycle 12 (end of study treatment), up to approximately 12 months (12 cycles, 28-day cycle length).
Progression-free survival (PFS)
PFS is defined as the time from the date of the first dose of elranatamab to the date of first documented disease progression, as defined in the IMWG response criteria, or death due to any cause, whichever occurs first.
Time frame: Every cycle from Cycle 1 Day 1 to end of Cycle 12 (end of study treatment), up to approximately 12 months (12 cycles, 28-day cycle length).
Overall survival (OS)
OS is defined as the time from the date of the first dose of elranatamab to the date of death, regardless of the actual cause of the participant's death.
Time frame: Every cycle from Cycle 1 Day 1 to end of 1 year survival follow-up, up to approximately 2 years (12 cycles, 28-day cycle length plus 1 year of survival follow-up).
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