622 - Randomized, open-label study of the biological effects of BLP25 liposome (L-BLP25) immunotherapy in rectal cancer patients undergoing neoadjuvant ch...

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Cancer Immunology and Immunotherapy
Rectal Cancer
Surgery and/or Radiotherapy of Cancer
Presenter Theo Ruers
Authors T. Ruers1, D. Aust2, M. van den Eynde3, G. Folprecht4, J. Carrasco5, M. Fuchs6, J. Smit7, A. Victor8, S. Quaratino9
  • 1Department Of Surgical Oncology, Nederlands Kanker Instituut - Antoni van Leeuwenhoek Ziekenhuis, 1066CX - Amsterdam/NL
  • 2Institute Of Pathology, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden/DE
  • 3Medical Oncology, Cliniques universitaires St-Luc, 1200 - Brussels/BE
  • 4Department Of Internal Medicine I, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden/DE
  • 5Medical Oncology, Grand Hopital de Charleroi, 6000 - Charleroi/BE
  • 6Klinikum Bogenhausen, München/DE
  • 7Internal Medicine, Gelre Ziekenhuizen, Apeldoorn/NL
  • 8Global Biostatistics/oncology, Merck KGaA, Darmstadt/DE
  • 9Global Clinical Development, Merck KGaA, Darmstadt/DE

Abstract

Background

Neoadjuvant chemoradiotherapy (NCR) followed by radical resection is the standard of care for patients with stage II-III rectal cancer. L-BLP25 (Stimuvax®) is an antigen-specific cancer immunotherapeutic agent targeting the mucin 1 (MUC1) antigen. It may act by inducing the proliferation of interferon (IFN)-γ secreting MUC1-specific CD4+ T-cells and the generation of cytotoxic T lymphocytes capable of killing MUC1-expressing tumours. In the SPRINT (Stimuvax® [L-BLP25] in Rectal cancer In Neoadjuvant chemoradioTherapy) study, we will evaluate immune responses to L-BLP25 in patients with rectal cancer undergoing NCR.

Study design

SPRINT is a phase II, multi-centre, open-label study in which patients (n = 24/arm) with resectable stage II-III rectal cancer are randomized to NCR (capecitabine 825 mg/m2 twice-daily for 5–7 d/wk; 45–52 Gy in fractions of 1.8/2 Gy for ≥5 wk) alone, NCR + L-BLP25, or NCR + L-BLP25 + cyclophosphamide (CPA). L-BLP25 is administered as 8 consecutive weekly subcutaneous doses (930 µg) beginning on the first day of NCR, followed by a final injection 7–9 d before surgery. CPA (300 mg/m2; maximum 600 mg) is given as a single intravenous infusion 3 d before the first L-BLP25 dose. Surgery will be performed 6–8 wk after the end of NCR.

The primary objective is to assess L-BLP25-induced changes in immune response profile. The intra-tumoural response will be evaluated based on analysis of tumour-infiltrating lymphocytes (especially CD8+ and CD45RO+). Peripheral antigen-specific response will be assessed by measuring IFN-γ secretion by peripheral blood mononuclear cells (ELIspot assay) in response to MUC1 and carcinoembryonic antigen (CEA) as a test for ‘antigen spreading’. Secondary objectives include the assessment of additional immunological changes and correlation of intratumoural, peripheral and skin delayed-type hypersensitivity responses. Safety and pathological anti-tumour responses in resection specimens will be evaluated.

Disclosure

A. Victor: Anja Victor is an employee of Merck KGaA Germany.

S. Quaratino: Sonia Quaratino is an employee of Merck KGaA.

All other authors have declared no conflicts of interest.