Clinical and pharmacologic evaluation of two dose levels of intetumumab (CNTO 95) in patients with melanoma or angiosarcoma.

Abstract

PURPOSE:

In this Phase 1, multicenter, open-label study, intetumumab (CNTO 95), a fully human anti-αv integrin monoclonal antibody was evaluated for safety, pharmacokinetics, and pharmacodynamic activity in patients with melanoma or angiosarcoma.

PATIENTS AND METHODS:

Patients with histologically-confirmed inoperable melanoma or angiosarcoma refractory to standard treatment were allocated to treatment with 10 mg/kg or 20 mg/kg intetumumab, administered once every 3 weeks for up to four cycles unless unacceptable toxicity or disease progression occurred. Extended dosing was available for patients who responded with stable disease or better.

RESULTS:

Eight patients received 10 mg/kg and 11 received 20 mg/kg intetumumab. Baseline patient characteristics were comparable between treatment groups; 18 patients had metastatic malignant melanoma and one had angiosarcoma. No dose-limiting toxicities were observed. Headache was the most common adverse event across both dose groups. Vomiting, nausea and chills were more common, and uveitic reactions lasted longer, in patients treated with 20 mg/kg compared with 10 mg/kg intetumumab. No patient developed antibodies to intetumumab. Intetumumab drug exposure as assessed by area under the curve and maximum serum concentration appeared to increase approximately dose-proportionally from 10 to 20 mg/kg, while volume of distribution remained constant for both doses. Stable disease was observed in two patients with metastatic malignant melanoma (one in each dose group) for at least 6 weeks.

CONCLUSIONS:

In patients with metastatic malignant melanoma and angiosarcoma in this study, intetumumab demonstrated manageable toxicity, was well tolerated, and presented approximately dose-proportional pharmacokinetics for the 10 mg/kg and 20 mg/kg doses.

• Authors: Steven J O'Day, Anna C Pavlick, Mark R Albertini, Omid Hamid, Heidi Schalch, Zhihui Lang, Jie Ling, Marielena Mata, Manjula Reddy, Brenda Foster
• Journal: Investigational new drugs (Invest New Drugs) Vol. 30 Issue 3 Pg. 1074-81 (Jun 2012) ISSN: 1573-0646 [Electronic] United States
• PMID: 21331745 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Biomarkers, Tumor
• Integrins
• BRAF protein, human
• Proto-Oncogene Proteins B-raf
• intetumumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (administration & dosage, adverse effects, pharmacokinetics)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents (administration & dosage, adverse effects, pharmacokinetics)
• Area Under Curve
• Biomarkers, Tumor (blood)
• Female
• Genes, ras (genetics)
• Hemangiosarcoma (drug therapy, genetics, metabolism)
• Humans
• Integrins (blood)
• Male
• Melanoma (drug therapy, genetics, metabolism)
• Middle Aged
• Proto-Oncogene Proteins B-raf (genetics)
• Skin Neoplasms (drug therapy, genetics, metabolism)
• Soft Tissue Neoplasms (drug therapy, genetics, metabolism)