RecruitingPhase 2NCT07382739

A Phase 2 Study of Radiotherapy-induced Immune Priming to Enhance Elranatamab (Elra) in Relapsed Refractory Multiple Myeloma (RRMM) With Extramedullary Disease (EMD) and Paramedullary Disease (PMD) "PRIME-EMD-PMD"

Sponsor

M.D. Anderson Cancer Center

Enrollment

34 participants

Start Date

Mar 31, 2026

Study Type

INTERVENTIONAL

Conditions

Relapsed Refractory Multiple Myeloma (RRMM)Extramedullary Disease in Multiple Myeloma PMD Phase 2 Radiotherapy-Induced Immune Priming Elranatamab Paramedullary Disease

Summary

To learn if low doses of radiation therapy can help the drug elranatamab enhance the killing effect of the cancer cells.

Eligibility

Inclusion Criteria21

RRMM exposed to IMID, PI, anti-CD38 mAb, relapsed or refractory to at least one prior line of therapy (LOT), progressed on or after the last regimen:
Relapsed disease: progressive disease (PD) >60 days after cessation of prior therapy
Refractory disease: PD <=60 days after cessation of prior therapy, <25% reduction in paraprotein (monoclonal protein \[M-protein\] or serum free light chains \[sFLC\]) or measurements of EMD/PMD
Diagnosis of relapsed or refractory multiple myeloma as indicated by progression by IMWG criteria
At least one locus of EMD or PMD present on imaging (either PET/CT or magnetic resonance imaging \[MRI\]):
EMD: extramedullary plasmacytoma, not a contiguous extension from a bone lesion.
PMD: paraskeletal plasmacytoma, contiguous extension from a bone lesion At least one locus of EMD/PMD that was not previously radiated and can be treated with radiation
Hematology (supportive care is allowed, including transfusions and granulocyte colony stimulating factor (G-CSF), if cytopenia is deemed secondary to myeloma disease burden):
Hemoglobin (Hgb) >=7g/dL
Platelet>=50K/uL
Absolute neutrophil count (ANC) >=0.75K/uL
Chemistry:
Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) <=2.5 x upper
limit of normal (ULN)
Total bilirubin (TBili) <=1.5ULN (except for a known history of Gilbert syndrome)
Creatinine clearance (CrCL) >=30mL/min/1.73m2
Eastern Cooperative Oncology Group Performance Status (ECOG PS) <=2, unless ECOG PS due to pain/morbidity secondary to underlying myeloma disease, with the potential of improved ECOG PS to <=2.
All participants must be either
Not of childbearing potential, or
Practicing at least 1 highly effective method of contraception until 6 months after the last dose of study treatment.
Childbearing age female participantsmust have a negative serum pregnancy test at screening and must agree to further pregnancy tests during the study.

Exclusion Criteria18

Prior or concurrent exposure to any of the following in the specified time frame prior to the first dose of Elra treatment:
Within 14 days or at least 5 half-lives, whichever is less, of any investigational treatment
Within 7 days of IMIDs, PI, anti-CD38 mAb, or cytotoxic systemic myeloma therapies
Within 12 weeks of autologous stem-cell therapy (ASCT) or 6 months of AlloSCT and has to be off immunosuppressive agents >=42 days without signs of graft versus host disease (GVHD)
Within 2 weeks of major surgery
Within 6 months of cerebrovascular accident (CVA) events
Waldenstrom, POEMS, Amyloidosis, ongoing plasma cell leukemia (PCL)
History of Human Immunodeficiency Virus (HIV)
Active, uncontrolled HBV infection despite antiviral therapy.
Uncontrolled cardiac, pulmonary, gastrointestinal (GI), hepatic, renal, central nervous system(CNS) diseases not due to myeloma, at the discretion of investigator, that are not a candidate for T cell engager (TCE) therapy
Uncontrolled or recurrent infections
Autoimmune disease requiring systemic treatment (except for low dose steroids, equivalent to 10mg/day or less of prednisone)
Disabling psychiatric conditions, substance abuse (alcohol, or drug), dementia, altered mental status
Any other active malignancies within 5 years of completing treatment (with the exception of hormonal therapies for breast or prostate cancer) and >minimal risk of recurrence
Myelodysplastic syndromes (MDS)
Any issues that may impair the ability of the participant to receive or tolerate the planned treatment, to understand the informed consent, or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant or that would prevent, limit, or confound the protocol specified assessments.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to Elra or other agents used in study.
History or possible non-compliance with recommended treatments