Table 1 Inclusion and Exclusion Criteria

1) Signed informed consent form.

2) Patients aged ≥18 years.

3) Locally-advanced rectal cancer cT2 N1–3, cT3/T4a N0–3

4) <  12 cm from anal verge.

5) Histologically proven rectal adenocarcinoma.

6) ECOG performance score ≤ 1.

7) Have adequate organ function by meeting the following:

 • Absolute neutrophil count (ANC) ≥ 1.5 × 109/L;

 • Platelet count ≥100 × 109/L;

 • Hemoglobin ≥9 g/dL;

 • Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range;

 • AST and ALT levels ≤2.5 × ULN or AST and ALT levels ≤5 x ULN (for subjects with documented metastatic disease to the liver);

 • Estimated creatinine clearance ≥30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method).

8) Negative serum or urine pregnancy test at screening for women of childbearing potential.

1) Distant metastasis (M1).

2) Patients with T2 N0 or T4b.

3) Recurrent rectal cancer.

4) Symptoms or history of peripheral neuropathy.

5) Prior radiotherapy or chemotherapy.

6) Current use of immunosuppressive medication except for the following:

 - Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);

 - Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or equivalent;

 - Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).

7) Concurrent treatment with a non-permitted drug.

8) Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent.

9) Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines.

10) Active infection requiring systemic therapy.

11) Known history of testing positive for the human immunodeficiency virus or known acquired immunodeficiency syndrome.

12) Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).

13) Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3).

14) Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (<  6 months prior to enrollment), myocardial infarction (<  6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.

15) Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator’s judgment are acceptable.

16) Prior organ transplantation including allogenic stem-cell transplantation.

17) Any psychiatric condition that would prohibit the understanding or rendering of informed consent.