Multicenter, open label, phase II clinical trial evaluating the combination of elranatamab with mezigdomide and dexamethasone in patients with relapsed/refractory multiple myeloma

Prior treatment

• Use of any antimyeloma therapy within 14 days prior to day 1 of cycle 1
• Stem cell transplant within 12 weeks prior to enrolment, active GVHD or active immunosuppressive therapy for GVHD
• Radiation therapy, other than local palliative therapy, for myeloma associated bone lesions within 14 days prior to day 1 of cycle 1
• Major surgery 14 days prior to initiating study therapy / prior to day 1 of cycle 1
• Prior therapy with mezigdomide or any BCMA bispecific agent. Prior therapy with a BCMA-targeted CAR T-cell therapy or ADC are allowed if >6 months have elapsed from the last dose
• Administration of live or live-attenuated vaccines within 30 days prior to the day 1 of cycle 1
• Prior history of neoplastic disease/malignancies other than MM in the last 5 years (except for basal cell carcinoma, skin epithelioma or carcinoma in situ of any site [i.e., breast, cervix])

Other illness

• Any serious medical condition or psychiatric illness that would interfere in understanding of the informed consent form
• Patient has a known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to mezigdomide or drugs chemically related to mezigdomide, or any of the excipients contained in the formulation of the study treatment
• Participant has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to other bispecific antibodies
• Any serious medical condition that places the subject at an unacceptable risk if he or she participates in this study
• Subjects with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis and lupus, that likely need additional steroid or immunosuppressive treatments in addition to the study treatment
• Other plasma cell disorders/associated syndromes, e.g. plasma cell leukemia, POEMS, amyloidosis
• Relevant diseases or adverse clinical conditions as defined in the study protocol
• Patient is known to be positive for human immunodeficiency virus (HIV), chronic or active hepatitis B, active hepatitis A, or active hepatitis C. In case of doubt, viral load must be negative

Lab values

• Left ventricular ejection fraction (LVEF) <50%

Other

• Women who are pregnant or breastfeeding, or who intends to become pregnant during participation in the study, and men and women of reproductive potential who are not using effective contraceptive methods (double barrier method, intrauterine device, oral contraception)
• Patient is simultaneously enrolled in other interventional clinical trial
• Patients with non-adequate hematological and/or non-hematological parameters defined in the study protocol

• Patient is, in the investigator’s opinion, willing and able to adhere/comply with visit schedule and other protocol requirements
• All prior relevant treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0 must be ≤grade 1 at the time of enrolment
• Reproductive status as per protocol requirements
• Patient must be able to understand the study procedures
• Patients aged 18 years at the time of signing the informed consent form
• Patients have documented diagnosis of MM according to the IMWG criteria (Lancet Oncol 2014)
• Patients have a relapsed MM who have previously received treatment with at least one line of antimyeloma therapy
• Patients must have documented disease progression during or after their last antimyeloma regimen
• Patients must have received prior treatment with a lenalidomide-containing regimen and must be intolerant or refractory to it, defined as occurrence of disease progression on lenalidomide or within 60 days after the last dose of treatment to lenalidomide
• Patient must have a measurable disease
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2