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Ref Type Journal Article
PMID (26463709)
Authors Meulendijks D, Jacob W, Martinez-Garcia M, Taus A, Lolkema MP, Voest EE, Langenberg MH, Fleitas Kanonnikoff T, Cervantes A, De Jonge MJ, Sleijfer S, Soerensen MM, Thomas M, Ceppi M, Meneses-Lorente G, James I, Adessi C, Michielin F, Abiraj K, Bossenmaier B, Schellens JH, Weisser M, Lassen UN
Title First-in-Human Phase I Study of Lumretuzumab, a Glycoengineered Humanized Anti-HER3 Monoclonal Antibody, in Patients with Metastatic or Advanced HER3-Positive Solid Tumors.
Journal Vol Issue Date Pages Journal Short Title
Clinical cancer research : an official journal of the American Association for Cancer Research 22 4 2016 Feb 15 877-85 Clin Cancer Res
URL
Abstract Text A first-in-human phase I study was conducted to characterize safety, efficacy, and pharmacokinetic (PK) and pharmacodynamic (PD) properties of lumretuzumab, a humanized and glycoengineered anti-HER3 monoclonal antibody, in patients with advanced cancer.Twenty-five patients with histologically confirmed HER3-expressing tumors received lumretuzumab (100, 200, 400, 800, 1,600, and 2,000 mg) every two weeks (q2w) in 3+3 dose-escalation phase. In addition, 22 patients were enrolled into an extension cohort at 2,000 mg q2w.There were no dose-limiting toxicities. Common adverse events (any grade) included diarrhea (22 patients, 46.8%), fatigue (21 patients, 44.7%), decreased appetite (15 patients, 31.9%), infusion-related reactions (13 patients, 27.7%), and constipation (10 patients, 21.3%). The peak concentration (Cmax) and area under the concentration-time curve up to the last measurable concentration (AUClast) of lumretuzumab increased more than dose proportionally from 100 mg up to 400 mg. Linear PK was observed with doses ≥ 400 mg q2w indicating target-mediated drug disposition saturation. Downregulation of HER3 membranous protein was observed in on-treatment tumor biopsies from 200 mg, and was maximal at and above 400 mg. An ex vivo assay demonstrated increased activation potential of peripheral NK lymphocytes with lumretuzumab compared with a non-glycoengineered anti-HER3 antibody. Ten patients (21.3%) had stable disease and remained on study at a median of 111 days (range, 80-225 days).Lumretuzumab was well tolerated and showed evidence of clinical activity. Linear serum PK properties and plateauing of PD effects in serial tumor biopsies indicate optimal biologically active doses of lumretuzumab from 400 mg onwards.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Lumretuzumab Lumretuzumab 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
Lumretuzumab RG7116|RO5479599 HER3 (ERBB3) Antibody 28 Lumretuzumab (RO5479599) is a humanized anti-Her3 (ERBB3) antibody that binds to and inhibits human epidermal growth factor receptor signaling, leading to growth inhibition in tumors (PMID: 26463709, PMID: 31423336).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References