This is an open-label phase 2 study of elranatamab in combination with isatuximab administered subcutaneously in patients with relapsed and refractory multiple myeloma (RRMM) who have received at least one prior line of therapy and who have had previous treatment with both immunomodulatory drugs (IMiDs) and a proteasome inhibitor (PI). The subcutaneous injection method of isatuximab administration, including the device used to administer isatuximab, is investigational.
This phase 2, single center, open-label study will enroll 30 patients with relapsed and refractory multiple myeloma (RRMM) who have received at least one prior line of therapy and who have had previous treatment with both immunomodulatory drugs (IMiDs) and a proteasome inhibitor (PI). Participants with prior therapy with anti-CD38 and anti-B cell maturation antigen (BCMA) target except an anti-BCMA T cell engager (TCE) may be eligible. This research is being done to see if the study drugs, elranatamab and isatuximab-irfc, reduce the risk of worsening disease and to evaluate the possible risks of the study drugs. Elranatamab is an FDA approved treatment for RRMM. Isatuximab is FDA approved as a treatment option for RRMM when administered intravenously (IV), however isatuximab will be administered as a subcutaneous (SC) infusion (injected under the skin) in this study which is not FDA approved and is investigational. Isatuximab will be administered subcutaneously using an investigational device called the on-body delivery system. The first six patients who complete Cycles 1 and 2 will be assessed for safety and adverse events prior to enrolling all other patients. The research involves screening for eligibility, study treatment and study visits, and follow-up visits. In the beginning (Day 1) of Cycle 1, there may be a 2-8 day inpatient visit so participants can be monitored during their first dose of isatuximab + elranatamab. Participants will receive study treatment until disease progression, unacceptable toxicity, or withdrawal for a maximum of 24 cycles, and will be followed every 3 months for up to 5 years after their final dose.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
Subcutaneously injected study drug, usually into the abdomen or lower stomach. Each vial of elranatamab contains a sufficient amount of product to ensure an extractable volume of 1.9 mL at a concentration of 40 mg/mL. The dosing is as follows: * Cycle 1 Day 1: 12 mg/0.3 mL; * Cycle 1 Day 4: 32 mg/0.8 mL; * Cycle 1 Day 8, 15, 22: 76 mg/1.9 mL; * Cycles 2-6, Day 1 and 15: 76 mg/1.9 mL; * Cycles 7-12, Day 1: 76 mg/1.9 mL; * Cycles 13-24, Day 1 of Cycles 13, 16, 19, 22 (every 12 weeks): 76 mg/1.9 mL
Isatuximab (SAR650984) is an IgG1 derived monoclonal antibody binding selectively the human CD38 membrane protein. Subcutaneously (SC) injected study drug with each vial containing 140 mg/mL (1400 mg/10mL) isatuximab. Isatuximab SC will be injected using the investigational OBDS and in the following doses: * Cycles 2-6, Day 1 and 15: 1400 mg/10 mL * Cycles 7-12, Day 1: 1400 mg/10 mL * Cycles 13-24, Day 1 of Cycles 13, 16, 19, 22 (every 12 weeks): 1400 mg/10 mL
Massachusetts General Hospital
Boston, Massachusetts, United States
RECRUITINGBeth Israel Deaconess Medical Center
Boston, Massachusetts, United States
RECRUITINGDana Farber Cancer Institute
Boston, Massachusetts, United States
NOT_YET_RECRUITINGObjective response rate (ORR)
Objective Response will be classified using the International Myeloma Working Group (IMWG) Uniform Response criteria. The rate (ORR) will be calculated using a Simon's two-stage design to test the null hypothesis that the ORR ≤ 0.40 versus the alternative that ORR ≥ 0.60. All patients who receive at least one complete cycle of treatment will be included in a response evaluation. Participants who do not complete cycle 1 (i.e., due to disease progression or who die prior to the end of cycle 1) will not be considered evaluable for response; these participants may be replaced. In the first stage, 22 patients will be accrued. If there are 10 or fewer responses in these 22 patients, the study will be stopped. Otherwise, study will continue to enroll to a total of 30. The null hypothesis will be rejected if 16 or more responses are observed in 30 patients.
Time frame: Day 1 to 2 years post-treatment.
Incidence of Drug Related Toxicities
All participants who receive at least one dose of study treatment will be evaluable for toxicity. CTCAE v5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) CRS and ICANS grading criteria will be used. Adverse events will be summarized on all patients treated. The number of drug related toxicities, and details (categorization and grading) will be described.
Time frame: Day 1 to 30 days post-treatment (30 days post last dose). Participants can receive treatment until disease progression, unacceptable toxicity, or withdrawal.
Median Progression Free Survival (PFS)
PFS is defined as the time from start of treatment to disease progression or death from any cause. Patients who have not progressed or died are censored at the date last known progression-free. PFS will be determined according to Kaplan-Meier methodology.
Time frame: Day 1 through end of follow-up, up to 5 years.
Median Overall Survival (OS)
OS is defined as the time from registration to death due to any cause, or censored at date last known alive. Median OS will be determined according to Kaplan-Meier methodology.
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NONE
Enrollment
30
The On Body Delivery System (OBDS) also called Isatuximab SC Wearable Injection System, is a sterile, single-use, disposable, elastomeric, user-filled investigational medical device. The OBDD has a reservoir for the drug product (isatuximab). A self-contained, integrated needle (with manual insertion and automatic retraction mechanism) is provided within the OBDS. The OBDS will be used to inject isatuximab each time the participant receives isatuximab in this study. Study drug administration will be done by trained medical professionals in the clinic. The OBDS device will be prepared by the medical professional, placed on the abdomen using the adhesive (sticky) pads that are on the device, the study drug (isatuximab) will be injected, and then the device will be removed.
Time frame: Day 1 through end of follow-up, up to 5 years.
Rate of Minimal Residual Disease (MRD) status in participants who have achieved very good partial response (VGPR) or complete response (CR)
MRD assessment will be assessed by next generation sequencing via bone marrow aspirate whenever a bone marrow sample is obtained. Those with VGPR or CR (per IMWG) will be included in this assessment. The rate is number of MRD-negative compared to MRD-positive and will be reported at various time points (time of VGPR/CR/sCR (variable, 3-6 months on treatment) and after 12 and 24 months on treatment).
Time frame: Screening through 24 months on treatment.
Sustained minimal residual disease (MRD) negative status
Rate and number of participants with MRD negative status who have achieved VGPR or CR by IMWG response criteria and have sustained MRD negative status for ≥6 and ≥12 months. MRD assessment will be assessed by next generation sequencing via bone marrow aspirate whenever a bone marrow sample is obtained. Those with VGPR or CR (per IMWG) will be included in this assessment. For patients where CR has been sustained for ≥6 and ≥12 months, MRD evaluation will be repeated to confirm sustained MRD. For patients who are MRD-negative at time of VGPR with persistent VGPR or achieve a CR, MRD evaluation will be repeated to confirm sustained MRD ≥6 and ≥12 months apart. The rate is number of these participants with sustained MRD negative status compared to number without sustained MRD negative status.
Time frame: Day 1 through 24 months on treatment.