Final Analysis Of The Phase 1a/B Study Of Chimeric Fibril-Reactive Monoclonal Antibody 11-1f4 In Patients With Relapsed Or Refractory Al Amyloidosis

Background: AL amyloidosis has a very poor prognosis with a variable median survival of 12 to 18 months depending largely on the severity of organ involvement. Current treatment focusing on eliminating the plasma cell clone that produces amyloidogenic light chains have improved overall survival in these patients [ Kumar 2011]. However, the risk of early mortality remains high due to multi-organ dysfunction caused by persistent, insoluble amyloid fibril deposits. To address this, amyloid fibril-reactive monoclonal antibody (mAb) 11-1F4 was designed to target amyloid deposits by directly binding to a conformational epitope present on human light-chain amyloid fibrils. The mAb was tested in a murine (Mu) and later a chimeric (Ch) form in mice with induced human AL amyloidomas; to which there was rapid destruction of amyloid fibrils without any evidence of toxicity in the animals [ Hrncic 2000; Solomon 2003 ]. Confirmation of the mAb's specificity for amyloid fibrils was further demonstrated when the I-124 labeled Mu mAb was visualized in amyloid-laden organs on PET/CT imaging in human subjects [ Wall 2010 ]. These promising results led to the development of GMP-grade amyloid fibril-reactive chimeric IgG1 mAb 11-1F4 by NCI's Biological Resource Branch. Here we report the final data from the open-label, dose-escalation phase 1a/b study of Ch IgG1 mAb 11-1F4 (NCT02245867).