Elsevier

Annals of Oncology

Volume 21, Issue 2, February 2010, Pages 376-381
Annals of Oncology

original articles
phase I and pharmacolinetics
Phase I and pharmacokinetic study of lexatumumab (HGS-ETR2) given every 2 weeks in patients with advanced solid tumors

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Abstract

Background

Lexatumumab (HGS-ETR2) is a fully human agonistic mAb to the tumor necrosis factor-related apoptosis-inducing ligand receptor 2 that activates the extrinsic apoptosis pathway and has potent preclinical antitumor activity.

Materials and methods

This phase 1, dose escalation study assessed the safety, tolerability, pharmacokinetics (PKs) and immunogenicity of lexatumumab administered i.v. every 14 days in patients with advanced solid tumors.

Results

Thirty-one patients received lexatumumab over five dose levels (0.1–10 mg/kg). Most (26 of 31) received four or more cycles of treatment. One patient at 10 mg/kg experienced a possibly related dose-limiting toxicity of grade 3 hyperamylasemia. Nine patients achieved stable disease. One patient with chemotherapy-refractive Hodgkin's disease experienced a mixed response. Lexatumumab PKs were linear up to 10 mg/kg. At the 10 mg/kg dose, the mean (±standard deviation) t1/2b was 13.67 ± 4.07 days, clearance was 4.95 ± 1.93 ml/day/kg, V1 was 45.55 ml/kg and Vss was 79.08 ml/kg, indicating that lexatumumab distributes outside the plasma compartment. No human antihuman antibodies were detected.

Conclusions

Lexatumumab can be safely administered every 14 days at 10 mg/kg. The PK profile supports this schedule. Further evaluation of lexatumumab at this dose schedule is warranted, including combination trials with other agents.

Keywords

apoptosis
HGS-ETR2
lexatumumab
pharmacokinetics
phase I
TRAIL-R2

Cited by (0)

Present address: Department of Clinical Research, South Texas Accelerated Research Therapeutics, San Antonio, TX, USA.