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 Immunotherapy
Surgical oncology
Colon and Rectal Cancer
Therapy
Radiation oncology
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.