A Trial of a novel agent in participants with previously treated Immunoglobulin Light-Chain (AL) Amyloidosis

Prior treatment

• Previous anti-BCMA targeted therapy (including, but not limited to, bispecifics).
• Intolerance to dexamethasone that would prohibit treatment with trial therapy.

Other illness

• Amyloid-specific syndrome, such as carpal tunnel syndrome or skin purpura, as the only evidence of disease. The finding of isolated vascular amyloid in a bone marrow biopsy specimen or in a plasmacytoma is not indicative of systemic amyloidosis.
• All hematologic malignancies, with the exception of low-risk Philadelphia chromosome negative (Ph-) myeloproliferative neoplasms (MPNs) and low-risk myelodysplastic syndromes (MDS), not requiring treatment.
• Mayo stage IIIB cardiac disease at Screening (see Appendix K for the definition of Mayo stage IIIB of cardiac disease).

Lab values

• MM diagnosed as per the International Myeloma Working Group (IMWG) criteria, with the exception of monoclonal gammopathy of unknown significance (MGUS) or smoldering myeloma, not requiring treatment. Note: A MM diagnosis with a serum FLC ratio >100, as the only myeloma-defining event, does NOT constitute an exclusion.

Other

• Isolated soft-tissue involvement.
• Presence of non-AL amyloidosis.

• Must have a histologic diagnosis of AL amyloidosis and typed with immunohistochemistry/ immunofluorescence, immunoelectron microscopy, or mass spectrometry. In patients with biopsy-confirmed amyloidosis, ambiguous amyloid typing results, and cardiac involvement alone, a negative pyrophosphate (PYP) or technetium-99m (99mTc) and 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD-Tc99m) bone scan is required to distinguish cardiac involvement due to AL amyloidosis from amyloid transthyretin (ATTR) amyloidosis. Data from the initial diagnosis are accepted.
• Genetic testing must be negative for transthyretin mutations associated with hereditary amyloidosis, or immunohistochemistry/ immunofluorescence/ immunoelectron microscopy/ mass spectrometry of amyloid deposits must provide clear evidence of κ or λ light chains in patients who present with peripheral neuropathy or heart as the dominant organ involvement. Data from the initial diagnosis are accepted.
  • 3.Criterion modified per Amendment 1. 3.1 Age ≥18 years (and the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent.
• .Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 at screening and at C1D1 immediately prior to the start of administration of study treatment
• Must have Mayo stage I–IIIA cardiac disease at Screening (see Appendix K for the definition of Mayo stages of cardiac disease).
  • 6.Criterion modified per Amendment 1. 6.1 Patients must be relapsed and / or refractory and must have received at least 1 line of treatment, including Daratumumab/ Isatuximab/ other anti CD38 monoclonal antibodies and bortezomib either in the same regimen or in separate treatment lines administered sequentially. Patients must have received at least two cycles in the last line of therapy. Note: Refractory is defined as patients failing to achieve a VGPR with organ response in a regimen/line of therapy.
  • 7.Criterion modified per Amendment 1. 7.1 Must have measurable hematologic disease: a dFLC >20 mg/L with an abnormal κ/λ ratio (with Freelite® test kits, The Binding Site ) or presence of a monoclonal spike ≥0.5 g/dL.
• Criterion modified per Amendment 1.8.1 Must have at least one symptomatic organ involvement (heart, kidney, liver, lung, gastrointestinal [GI] tract or peripheral nervous system) at the time of AL-diagnosis (see Appendix B for the definition of symptomatic organ involvement).
  • 9.Criterion modified per Amendment 1.9.1 A wash-out period of at least 14 days from the date of the last administration of any previous antitumor therapy or investigational treatment, meaning that the patient must not have received any non-Amyloidosis, anticancer therapy or investigational treatment for at least 14 days prior to Cycle 1 Day 1 (C1D1) of this trial and must have completed all previous treatment prior to screening.