A Randomised, Phase II Study of Intetumumab, an Anti-αv-integrin MAb, Alone and with Dacarbazine in Stage IV Melanoma

Overview

Journal Br J Cancer

Specialty Oncology

Date 2011 Jul 14

PMID 21750555

Citations 60

Authors

S ODay

A Pavlick

C Loquai

D Lawson

R Gutzmer

J Richards

D Schadendorf

J A Thompson

R Gonzalez

U Trefzer

P Mohr

C Ottensmeier

D Chao

B Zhong

C J de Boer

C Uhlar

D Marshall

M E Gore

Z Lang

W Hait

P Ho

Affiliations

Soon will be listed here.

Abstract

Background: α(v) integrins are involved in angiogenesis and melanoma tumourigenesis. Intetumumab (CNTO 95) is a fully human anti-α(v)-integrin monoclonal antibody.

Methods: In a multicentre, randomised, phase II study, stage IV melanoma patients were randomised 1:1:1:1 to 1000 mg m(-2) dacarbazine+placebo (n=32), 1000 mg m(-2) dacarbazine+10 mg kg(-1) intetumumab (n=32), 10 mg kg(-1) intetumumab (n=33), or 5 mg kg(-1) intetumumab (n=32) q3w. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), adverse events, and pharmacokinetics.

Results: No statistically significant differences in efficacy were observed between groups. In the dacarbazine+placebo, dacarbazine+intetumumab, 10 mg kg(-1) intetumumab, and 5 mg kg(-1) intetumumab groups, median PFS was 1.8, 2.5, 1.4, and 1.4 months; median OS was 8, 11, 15, and 9.8 months; and ORR of complete+partial response was 10, 3, 6, and 0%. Nonlinear intetumumab pharmacokinetics and potential intetumumab-dacarbazine interactions were observed. Transient, asymptomatic, nonrecurring, grade 1-2, uveitic reactions that resolved spontaneously or with topical steroids were seen in 22-30% of intetumumab-treated patients. Low-grade infusion-reaction symptoms (headache, fatigue, nausea, vomiting, fever, chills) were observed, as expected, in 16-73% of dacarbazine-treated patients. No intetumumab-related myelosuppression, laboratory/electrocardiogram abnormalities, or deaths occurred.

Conclusion: With its favourable safety profile and a nonsignificant trend towards improved OS, intetumumab merits further investigation in advanced melanoma.

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