Trial of Nivolumab With FOLFOX After Chemoradiation in Rectal Cancer Patients

Phase II Trial to Evaluate the Addition of Nivolumab to Neoadjuvant Chemoradiation With FOLFOX for Locally Advanced Rectal Cancer

This is a phase II, prospective, open label, one-center study for evaluation of the addition of nivolumab to the chemotherapy phase of the neoadjuvant treatment for locally advanced rectal cancer patients. Subjects must have received no prior treatment for rectal cancer (chemotherapy, radiotherapy or surgery) and no prior treatment with checkpoint inhibitors.

Eligible subjects will receive chemoradiation for a period of 5 weeks, 6 cycles of chemo-immunotherapy (mFOLFOX6 + nivolumab) for a period of 12 weeks, once every 2 weeks, and will undergo surgery after 4 weeks.

Patients with cCR will be offered the alternative strategy of WW. Post-study systemic treatment, up to 4 cycles of mFOLFOX6, will be left to the discretion of the treating physician. This will be started 4-8 weeks post-operatively, or immediately after the demonstration of cCR in patients determined to undergo WW.

Inclusion Criteria:

• Signed written IRB approved informed consent
• Age ≥ 18 years
• ECOG PS 0-1
• Subjects with histologically confirmed primary (non-recurrent) locally advanced rectal adenocarcinoma
• Stage T3-4 N0 or TX N+ according to baseline rectal EUS and PET-CT
• Patients who are planned for neoadjuvant chemoradiation and are surgical candidates
• No prior chemotherapy, radiotherapy or surgery for rectal cancer
• No prior radiotherapy to the pelvis, for any reason
• Presence of adequate contraception in fertile patients
• Women of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug
• Women must not be breastfeeding
• Ability to swallow tablets
• No previous (within the last 5 years) or concurrent malignancies, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix or basal cell carcinoma of the skin

Exclusion Criteria:

• Active autoimmune disease. [Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll]
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Pregnancy or breastfeeding