Background: NACR for LARC has been standard for 2 decades. Pathologic complete response (pCR) associates with improved survival and is an outcome surrogate in NACR clinical trials. In modern phase III trials of NACR in LARC, pCR ranges 15-20%. CET improves response rates in KRAS wild-type (KRAS-WT) metastatic colorectal cancer. S0713 was designed to select patients (PTS) by KRAS-WT status to assess improvement in pCR with CET added to ICT and NACR for LARC. Methods: Eligibility: Stage II-III biopsy proven LARC, KRAS-WT, without bowel obstruction or prior therapy, adequate hematologic, hepatic and renal function, and performance status of 0-2. Peripheral neuropathy > grade 2 was exclusionary. Enrollment target was 80 eligible PTS with planned interim analysis after 40 PTS received all therapy; if < 7 pCR were observed at interim, the study was to close. Treatment consisted of ICT then NACR and surgery. Treatment regimen: Cycle 1: OX 50 mg/m2 day (d) 1,8,15,22,29, CET 400mg/m2 d1 then 250 mg/m2 d 8, 15, 22, 29 and CAP 825 mg/m2 p.o. BID Monday through Friday (M-F) d1-35; Rest d 36-49; Cycle 2: OX 50 mg/m2 d 50, 57, 71, 78, CET 250 mg/m2 d 50, 57, 64, 71, 78 and CAP 825 mg/m2 p.o. BID M- F d 50-85 with radiation 180 cGy/d M-F x 5 weeks (4500 cGy) followed by 540 cGy boost x 3 (stage II; 5040cGy) or 5 (stage 3; 5400cGy). Surgery occurred 3-8 weeks after NACR. 80 eligible PTS would give a power of 90% if true pCR > 35% at a significance of 0.04. The regimen would lack future interest if pCR < 20%. Results: From February 2009 to April 2013, 83 PTS registered; 5 were ineligible; 4 not treated. 74 were available for toxicity evaluation (TOX); 72 had available data; 62 PTS (86%) had surgery. 1 grade 5 TOX and 2 grade 4 TOX occurred. 7 PTS withdrew for TOX, 2 for other reasons. 18 of 62 PTS had pCR (25%, 95% CI 16-37%). 19 PTS (26%) had microscopic cancer; 35 PTS (49%) had minor/no response (10 no surgery). Conclusions: ICT and NACR with CET improved pCR over historical and recent rates of ~20%. Toxicity was generally acceptable. This approach can serve as a base for adding additional agents in KRAS-WT LARC. Additional analysis for resistance genes is ongoing. Clinical trial information: NCT00686166