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A Phase I First-in-Human Study of Nesvacumab (REGN910), a Fully Human Anti–Angiopoietin-2 (Ang2) Monoclonal Antibody, in Patients with Advanced Solid Tumors
- Source :
- Clinical Cancer Research. 22:1348-1355
- Publication Year :
- 2016
- Publisher :
- American Association for Cancer Research (AACR), 2016.
-
Abstract
- Purpose: Nesvacumab (REGN910) is a fully human immunoglobulin G1 (IgG1) monoclonal antibody that specifically binds and inactivates the Tie2 receptor ligand Ang2 with high affinity, but shows no binding to Ang1. The main objectives of this trial were to determine the safety, tolerability, dose-limiting toxicities (DLT), and recommended phase II dose (RP2D) of nesvacumab. Experimental Design: Nesvacumab was administered intravenously every two weeks with dose escalations from 1 to 20 mg/kg in patients with advanced solid tumors. Results: A total of 47 patients were treated with nesvacumab. No patients in the dose escalation phase experienced DLTs, therefore a maximum tolerated dose (MTD) was not reached. The most common nesvacumab-related adverse events were fatigue (23.4%), peripheral edema (21.3%), decreased appetite, and diarrhea (each 10.6%; all grade ≤ 2). Nesvacumab was characterized by linear kinetics and had a terminal half-life of 6.35 to 9.66 days in a dose-independent manner. Best response by RECIST 1.1 in 43 evaluable patients included 1 partial response (adrenocortical carcinoma) of 24 weeks duration. Two patients with hepatocellular carcinoma had stable disease (SD) > 16 weeks, with tumor regression and >50% decrease in α-fetoprotein. Analyses of putative angiogenesis biomarkers in serum and tumor biopsies were uninformative for treatment duration. Conclusions: Nesvacumab safety profile was acceptable at all dose levels tested. Preliminary antitumor activity was observed in patients with treatment-refractory advanced solid tumors. On the basis of cumulative safety, antitumor activity, pharmacokinetic and pharmacodynamic data, the 20 mg/kg dose was determined to be the RP2D. Clin Cancer Res; 22(6); 1348–55. ©2015 AACR.
- Subjects :
- Adult
Male
0301 basic medicine
Nesvacumab
Cancer Research
medicine.medical_specialty
Maximum Tolerated Dose
Peripheral edema
Antineoplastic Agents
Pharmacology
Antibodies, Monoclonal, Humanized
Gastroenterology
Angiopoietin-2
Young Adult
03 medical and health sciences
0302 clinical medicine
Pharmacokinetics
Neoplasms
Internal medicine
medicine
Humans
Aged
Neoplasm Staging
Aged, 80 and over
Dose-Response Relationship, Drug
business.industry
Cancer
Middle Aged
medicine.disease
Treatment Outcome
030104 developmental biology
Oncology
Tolerability
030220 oncology & carcinogenesis
Hepatocellular carcinoma
Pharmacodynamics
Monoclonal
Female
medicine.symptom
business
Biomarkers
Subjects
Details
- ISSN :
- 15573265 and 10780432
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....daffec72601e53d9f4772a4e480a3591