Tecemotide (L-BLP25) in Rectal Cancer

A Multi-center, Randomized, Open-label, Mechanism of Action Trial on the Biological Effects of the Therapeutic Cancer Vaccine Stimuvax® (L-BLP25) in Rectal Cancer Subjects Undergoing Neoadjuvant Chemoradiotherapy

The objective of this mechanistic study is to determine the impact of tecemotide (L-BLP25) administration on the mucinous glycoprotein 1 - (MUC1) specific immune response in subjects with newly diagnosed rectal cancer who are eligible for neoadjuvant therapy.

Tecemotide (L-BLP25) is designed to induce an immune response that may lead to immune rejection of tumor tissues that aberrantly express MUC1 antigen. MUC1 is highly expressed in all colorectal cancers and since the adaptive immune system plays a role in the prognosis of rectal cancer, it is reasonable to speculate that tecemotide (L-BLP25) administration might boost the tumor-specific immune response and increase the number of tumor-infiltrating lymphocytes (TILs).

Inclusion Criteria:

1. Male and female subjects with histologically documented resectable rectal adenocarcinoma in Stage 2-4
2. Availability of tumor biopsy sufficient for immunological analysis
3. Indication to receive neoadjuvant concomitant chemoradiotherapy consisting of a radiation dose of 45-52 Gy and capecitabine 825 mg/m^2 orally twice daily. The use of an equivalent schedule based on 5-FU is acceptable
4. Magnetic resonance imaging small pelvis / computed tomography thorax/abdomen (or X-ray thorax) to document absence of metastatic disease. Imaging must not be older than 6 weeks prior to randomization
5. Eastern Cooperative Oncology Group performance status of 0 or 1
6. Written informed consent
7. Greater than or equal to (>=) 18 years of age

Exclusion Criteria:

1. Previous chemotherapy and/or previous radiotherapy of the pelvic region
2. Relapsing disease
3. Previous vaccination with any MUC1 vaccine and other therapeutic cancer vaccines
4. Previous organ transplantation (bone marrow or solid organs)
5. Subjects with metastatic disease (except for solitary, resectable liver or lung metastases)
6. Inadequate hematological function (that is, platelet count less than 140*10^9 per liter [/L], or white blood cell less than 2.5*10^9/L, or hemoglobin less than 90 gram per liter). Clinically significant hepatic dysfunction (that is alanine aminotransferase greater than 2.5*upper limit of normal [ULN], or aspartate aminotransferase greater than 2.5*ULN, or bilirubin greater than 1.5*ULN). Inadequate renal function (that is serum creatinine greater than 1.5*ULN)
7. Autoimmune diseases
8. Recognized immunodeficiency disease including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; subjects who have hereditary or congenital immunodeficiencies
9. Clinically significant cardiac disease, for example, New York Heart Association Classes III-IV; uncontrolled angina, uncontrolled arrhythmia or uncontrolled hypertension, myocardial infarction in the previous 6 months as confirmed by medical history and an electrocardiogram
10. Other protocol defined exclusion criteria could apply