Study of Elranatamab for Relapsed or Refractory Myeloma in Patients Previously Exposed to Three-drug Classes
Status: Recruiting

The goal of this phase II, open-label, single-arm, multicenter study is to evaluate i) the efficacy and ii) safety of elranatamab monotherapy at the dose of 76 mg subcutaneously in participants with RRMM after at least one or two prior lines of therapy who have received prior treatment with immunomodulatory drugs, protease inhibitors, and anti-CD38 therapy and were refractory to the last line of therapy, defined as progression while receiving treatment or in the first 60 days after the last dose of treatment.

Efficacy refers to the rate of Undetectable Measurable Residual Disease at 6 and 12 months as per International Myeloma Working Group (IMWG) criteria evaluated by the investigators.

Safety refers to the measurement of:

i) Adverse events (AEs) and serious adverse events (SAEs) according to standard clinical and laboratory tests (hematology and chemistry, physical examination, vital sign measurements, and diagnostic tests).

ii) Incidence and severity of Cytokine Release Syndrome (CRS) and Immune effector cell associated neurotoxicity syndrome (ICANS) according to the American Society for Transplantation and Cellular Therapy (ASTCT) criteria.

iii) Incidence and severity of other neurotoxicities. iv) Incidence of cytopenias and infections

The study consists of a screening/baseline period, a treatment period, and a posttreatment follow-up period. The study includes a periodic review of safety data, that will be independently analyzed by the Data Safety Independent Committee (DSMC) and will recommend how to proceed with the study.

Eligibility:
- EligibilityCriteria: Inclusion Criteria:  Male or female, 18 years or older (at the time consent is obtained). Patient who, in the investigator's opinion, is able to comply with the protocol requirements. Prior diagnosis of MM as defined according to IMWG criteria. Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care. Relapse multiple myeloma patients that have received at least 1 or 2 prior lines of therapy including at least to one proteasome inhibitor (bortezomib, carfilzomib or ixazomib), one immunomodulatory drug (lenalidomide is mandatory and patients can be also have been exposed to pomalidomide) and at least one anti-CD38 monoclonal antibody (daratumumab or isatuximab). Patients must be refractory to the last line of therapy, defined as progression while receiving treatment or in the first 60 days after the last dose of treatment. Patient must have a measurable secretory disease defined as either serum monoclonal protein of ≥ 0,5 g/dl or urine monoclonal (light chain) protein ≥ 200 mg/24 h. For patients in whom disease is only measurable by serum FLC, the involved FLC should be ≥ 10mg/dL (100 mg/L), with an abnormal serum FLC ratio.  Exclusion Criteria:  Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), POEMS syndrome (defined by the presence of peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma-cells proliferative disorder, and skin changes) or plasma cell leukemia. Prior anti-BCMA treatment. Subject has peripheral neuropathy or neuropathic pain grade 2 or higher, as defined by the National Cancer Institute Terminology Criteria for Adverse Events (NCI CTCAE) Version 5. History of Guillain-Barré syndrome (GBS) or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy. Stem cell transplant within 12 weeks prior to enrolment. - HealthyVolunteers: No - Gender: All - MinimumAge: 18 Years - StdAgeList: Adult, Older Adult