Originally published as JCO Early Release 10.1200/JCO.2008.20.2515 on July 27 2009

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Phase I Dose Escalation, Pharmacokinetic and Pharmacodynamic Study of Naptumomab Estafenatox Alone in Patients With Advanced Cancer and With Docetaxel in Patients With Advanced Non–Small-Cell Lung Cancer

From the Department of Medical Oncology, and the Protocol Supportive Laboratory, Fox Chase Cancer Center, Philadelphia, PA; Active Biotech, Lund, Sweden; Christie Research Centre, Manchester, United Kingdom; the Department of Clinical Cancer Research, Norwegian Radium Hospital, Oslo, Norway; and the Department of Oncology, Rikshospitalet University Hospital, Copenhagen, Denmark.

Corresponding author: Hossein Borghaei, DO, MS, Department of Medical Oncology, Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111; hossein.borghaei{at}fccc.edu.

Purpose Two phase I studies were conducted of ABR-217620 alone or in combination with docetaxel. This is a recombinant fusion protein consisting of a mutated variant of the superantigen staphylococcal enterotoxin E (SEA/E-120) linked to fragment antigen binding moiety of a monoclonal antibody recognizing the tumor-associated antigen 5T4.

Patients and Methods Patients with non–small-cell lung cancer (NSCLC), pancreatic cancer (PC), and renal cell cancer (RCC) received 5 daily boluses of ABR-217620 (3-month cycles) in escalating doses to determine the maximum-tolerated dose (MTD; ABR-217620 dose escalation monotherapy [MONO] study). Doses were selected based on individual patient anti–SEA/E-120 titers pretreatment. Patients with NSCLC received 4 daily, escalating doses of ABR-217620 followed by docetaxel in 21-day cycles (ABR-217620 dose escalation combination with docetaxel [COMBO] study).

Results Thirty-nine patients were enrolled in the MONO study and 13 were enrolled in the COMBO study. The monotherapy MTD was 26 µg/kg (NSCLC and PC) and 15 µg/kg (RCC). Dose-limiting toxicities (DLTs) in the MONO study were fever, hypotension, acute liver toxicity, and vascular leak syndrome. In the COMBO study, the MTD was 22 µg/kg (neutropenic sepsis). Adverse events included grade 1 to 2 fever, hypotension, nausea, and chills. Treatment caused a systemic increase of inflammatory cytokines and selective expansion of SEA/E-120 reactive T-cells. Tumor biopsies demonstrated T-cell infiltration after therapy. Fourteen patients (36%) had stable disease (SD) on day 56 of the MONO study. Two patients (15%) in the COMBO study had partial responses, one in a patient with progressive disease on prior docetaxel, and five patients (38%) had SD on day 56.

Conclusion ABR-217620 was well tolerated with evidence of immunological activity and antitumor activity.

Supported in part by Grant No. P30 CA006927 from the National Cancer Institute, Bethesda, MD.

Presented in part at 2007 American Association for Cancer Research National Cancer Institute European Organisation for the Research and Treatment of Cancer International Conference on Molecular Targets and Cancer Therapeutics, October 22-26, 2007, San Francisco, CA.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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