A phase II study of a 5T4 oncofoetal antigen tumour-targeted superantigen (ABR-214936) therapy in patients with advanced renal cell carcinoma.
AuthorsShaw, David M
Connolly, Noel B
Patel, P M
Stern, Peter L
Hawkins, Robert E
AffiliationPaterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, UK. firstname.lastname@example.org
MetadataShow full item record
AbstractIn a phase II study, 43 renal cell carcinoma patients were treated with individualised doses of ABR-214936; a fusion of a Fab recognising the antigen 5T4, and Staphylococcal enterotoxin A. Drug was given intravenously on 4 consecutive days, treatment was repeated 1 month later. Treatment was associated with moderate fever and nausea, but well tolerated. Of 40 evaluable patients, 28 had disease control at 2 months, and at 4 months, one patient showed partial response (PR) and 16 patients stable disease. Median survival, with minimum follow-up of 26 months was 19.7 months with 13 patients alive to date. Stratification by the Motzer's prognostic criteria highlights prolonged survival compared to published expectation. Patients receiving higher drug exposure had greater disease control and lived almost twice as long as expected, whereas the low-exposure patients survived as expected. Sustained interleukin-2 (IL-2) production after a repeated injection appears to be a biomarker for clinical effect, as the induced-IL-2 level on the day 2 of treatment correlated with survival. The high degree of disease control and the prolonged survival suggest that this treatment can be effective. These findings will be used in the trial design for the next generation of drug, with reduced antigenicity and toxicity.
CitationA phase II study of a 5T4 oncofoetal antigen tumour-targeted superantigen (ABR-214936) therapy in patients with advanced renal cell carcinoma. 2007, 96 (4):567-74 Br. J. Cancer
JournalBritish Journal of Cancer
- 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.
- Authors: Borghaei H, Alpaugh K, Hedlund G, Forsberg G, Langer C, Rogatko A, Hawkins R, Dueland S, Lassen U, Cohen RB
- Issue date: 2009 Sep 1
- Phase II trial of Modified Vaccinia Ankara (MVA) virus expressing 5T4 and high dose Interleukin-2 (IL-2) in patients with metastatic renal cell carcinoma.
- Authors: Kaufman HL, Taback B, Sherman W, Kim DW, Shingler WH, Moroziewicz D, DeRaffele G, Mitcham J, Carroll MW, Harrop R, Naylor S, Kim-Schulze S
- Issue date: 2009 Jan 7
- Naptumomab estafenatox, an engineered antibody-superantigen fusion protein with low toxicity and reduced antigenicity.
- Authors: Forsberg G, Skartved NJ, Wallén-Ohman M, Nyhlén HC, Behm K, Hedlund G, Nederman T
- Issue date: 2010 Jun
- A prospective open-label single-arm phase II study of chimeric monoclonal antibody cG250 in advanced renal cell carcinoma patients.
- Authors: Varga Z, de Mulder P, Kruit W, Hegele A, Hofmann R, Lamers C, Warnaar S, Mala C, Ullrich S, Mulders P
- Issue date: 2003
- Superantigen-based immunotherapy: a phase I trial of PNU-214565, a monoclonal antibody-staphylococcal enterotoxin A recombinant fusion protein, in advanced pancreatic and colorectal cancer.
- Authors: Giantonio BJ, Alpaugh RK, Schultz J, McAleer C, Newton DW, Shannon B, Guedez Y, Kotb M, Vitek L, Persson R, Gunnarsson PO, Kalland T, Dohlsten M, Persson B, Weiner LM
- Issue date: 1997 May