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Clinical Trial
. 2011 Jul 26;105(3):346-52.
doi: 10.1038/bjc.2011.183. Epub 2011 Jul 12.

A randomised, phase II study of intetumumab, an anti-αv-integrin mAb, alone and with dacarbazine in stage IV melanoma

S O'Day  1 , 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; CNTO 95 Investigators
Collaborators, Affiliations
Clinical Trial

A randomised, phase II study of intetumumab, an anti-αv-integrin mAb, alone and with dacarbazine in stage IV melanoma

S O'Day et al. Br J Cancer. .

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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Conflict of interest statement

O’Day, Pavlick, Loquai, Lawson, Gutzmer, Richards, Schadendorf, Thompson, Gonzalez, Trefzer, Mohr, Ottensmeier, Chao, and Gore received institutional research grants from Centocor for conducting the study. Zhong, de Boer, Uhlar, Marshall, Lang, Hait, and Ho were employees of Centocor during the conduct of the study.

Figures

Figure 1
Figure 1
Patient flow. Twenty (15.5%) randomised patients did not meet the protocol-defined entry criteria, the majority (n=12, 9.3%) because of laboratory criteria violations. The most significant protocol violation was reported for one patient in the 10 mg kg−1 intetumumab+dacarbazine arm who had stage III melanoma at baseline and was excluded from analysis.
Figure 2
Figure 2
(A) Progression-free survival using Kaplan–Meier estimates, randomised patients. (B) Overall survival using Kaplan–Meier estimates, randomised patients.
Figure 3
Figure 3
Scatter plot of 1-year overall survival rates from this study and of historical data from the meta-analysis by Korn et al (2008). The dotted line at y=0.25 represents the mean 1-year overall survival rate and the curved lines represent the 95% confidence bounds of all agents included in the meta-analysis. Reproduced with the kind permission of the American Society of Clinical Oncology from Korn et al (2008).
See this image and copyright information in PMC

References

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