Faculty Opinions recommendation of First-in-Human Phase I/II Study of NEOD001 in Patients With Light Chain Amyloidosis and Persistent Organ Dysfunction.
Year: 2018
Type: peer-review
Abstract: PurposeLight chain (AL) amyloidosis is caused by the accumulation of misfolded proteins, which induces the dysfunction of vital organs.NEOD001 is a monoclonal antibody targeting these misfolded proteins.We report interim data from a phase I/II dose-escalation/expansion study of NEOD001 in patients with AL amyloidosis and persistent organ dysfunction (NCT01707264). Patients and MethodsPatients who had completed at least one previous anti-plasma cell-directed therapy, had partial hematologic response or better, and had persistent organ dysfunction received NEOD001 intravenously every 28 days.Dose levels of 0.5, 1, 2, 4, 8, 16, and 24 mg/kg were evaluated (3 + 3 study design).Primary objectives were to determine the maximum tolerated dose and the recommended dose for future studies and to evaluate safety/tolerability.Secondary and exploratory objectives included pharmacokinetics, immunogenicity, and organ responses on the basis of published consensus criteria. ResultsTwenty-seven patients were enrolled in seven cohorts (dose-escalation component).No drugrelated serious adverse events (AEs), discontinuations because of drug-related AEs, dose-limiting toxicities, or antidrug antibodies were reported.The most frequent AEs were fatigue, upper respiratory tract infection, cough, and dyspnea.Recommended dosing was 24 mg/kg.Pharmacokinetics support intravenous dosing every 28 days.Of 14 cardiac-evaluable patients, eight (57%) met the criteria for cardiac response and six (43%) had stable disease.Of 15 renal-evaluable patients, nine (60%) met the criteria for renal response and six (40%) had stable disease. ConclusionMonthly infusions of NEOD001 were safe and well tolerated.Recommended future dosing was 24 mg/kg.Organ response rates compared favorably with those reported previously for chemotherapy.A phase II expansion is ongoing.A global phase III study (NCT02312206) has been initiated.Antibody therapy targeting misfolded proteins is a potential new therapy for the management of AL amyloidosis.
Author: Parameswaran Hari
Institution: Medical College of Wisconsin
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4239754945