Short-course Radiation Followed by mFOLFOX-6 Plus COMPOUND 2055269 for Locally-advanced Rectal Adenocarcinoma

Inclusion Criteria:

1. Patients aged ≥18 years.
2. Locally-advanced rectal cancer (cT2 N1-3, cT3 N0-3, evidence of extramural vascular ormesorectal fascia involvement).
3. <12 cm from anal verge.
4. Histologically proven rectal adenocarcinoma.
5. ECOG performance score ≤ 1.
6. 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 withdocumented metastatic disease to the liver);
• Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft- Gaultformula (or local institutional standard method).

7. Negative serum or urine pregnancy test at screening for women of childbearingpotential.
8. Highly effective contraception for both male and female subjects throughout the studyand for at least 30 days after last COMPOUND 2055269 treatment administration if therisk of conception exists.

Exclusion Criteria:

1. Distant metastasis (M1).
2. Patients with T2 N0 or T4.
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.,intraarticular injection);
• Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone orequivalent;
• Steroids as premedication for hypersensitivity reactions (e.g., CT scanpremedication).

7. Active autoimmune disease that might deteriorate when receiving an immunostimulatoryagent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroiddiseases not requiring immunosuppressive treatment are eligible.
8. Vaccination within 4 weeks of the first dose of COMPOUND 2055269 and while on trialsis prohibited except for administration of inactivated vaccines.
9. Active infection requiring systemic therapy.
10. Known history of testing positive for the human immunodeficiency virus or knownacquired immunodeficiency syndrome.
11. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positiveHBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).
12. Known prior severe hypersensitivity to investigational product or any component in itsformulations, including known severe hypersensitivity reactions to monoclonalantibodies (NCI CTCAE v4.03 Grade ≥ 3).
13. Clinically significant (i.e., active) cardiovascular disease: cerebral vascularaccident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 monthsprior to enrollment), unstable angina, congestive heart failure (≥ New York HeartAssociation Classification Class II), or serious cardiac arrhythmia requiringmedication.
14. 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 safetyrisk based on investigator's judgment are acceptable.
15. Prior organ transplantation including allogenic stem-cell transplantation.
16. Other severe acute or chronic medical conditions including immune colitis,inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatricconditions including recent (within the past year) or active suicidal ideation orbehavior; or laboratory abnormalities that may increase the risk associated with studyparticipation or study treatment administration or may interfere with theinterpretation of study results and, in the judgment of the investigator, would makethe patient inappropriate for entry into this study.
17. Concurrent treatment with a non-permitted drug.
18. Patients suspected by the physician that he/she will not compliant to the protocolconduct.
19. Pregnant or breastfeeding patients.
20. Patient participating in another clinical trial.
21. Patient who is not willing to sign the consent form.
22. Any psychiatric condition that would prohibit the understanding or rendering ofinformed consent.
23. Legal incapacity or limited legal capacity patients receiving other oncology specificmedication not authorized in the protocol.