GASTROINTESTINAL CANCER—COLORECTAL AND ANAL 3500 Oral Abstract Session Final overall survival for the phase III KN177 study: Pembrolizumab versus chemotherapy in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). Thierry Andre, Kai-Keen Shiu, Tae Won Kim, Benny Vittrup Jensen, Lars Henrik Jensen, Cornelis J. A. Punt, Denis Michel Smith, Rocio Garcia-Carbonero, Julia Alcaide, Peter Gibbs, Christelle De La Fouchardiere, Fernando Rivera, Elena Elez, Johanna C. Bendell, Dung T. Le, Takayuki Yoshino, Wen Yan Zhong, David R. Fogelman, Patricia Marinello, Luis A. Diaz; Sorbonne Universite� and Ho^pital- Saint Antoine, Paris, France; University College Hospital, NHS Foundation Trust, London, United King- dom; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Herlev and Gentofte Hospital, Herlev, Denmark; University Hospital of Southern Denmark, Vejle, Denmark; Depart- ment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, Netherlands; Bordeaux University Hospital, Bordeaux, France; Hospital Universitario 12 de Octubre, Imas12, CNIO, UCM, Madrid, Spain; Hospital Regional Universitario de Malaga, Ma�laga, Spain; Western Health, St. Al- bans, Australia; Centre Le�on Be�rard, Lyon, France; Hospital Universitario Marque�s de Valdecilla, IDIV- AL, Santander, Spain; Vall dHebron Institute of Oncology, Barcelona, Spain; Sarah Cannon Research Institute/Tennessee Oncology PLLC, Nashville, TN; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; National Cancer Center Hospital East, Kashiwa, Japan; MSD China, Shanghai, China; Merck & Co., Inc., Kenilworth, NJ; Memorial Sloan Kettering Cancer Center, New York, NY Background: In the phase III, randomized open-label KEYNOTE-177 (NCT02563002) study 1L pem- brolizumab (pembro) versus chemotherapy (chemo) provided superior progression-free survival (PFS) at second interim analysis (IA2) in patients (pts) with MSI-H/dMMR mCRC. The study continued to final analysis of overall survival (OS), planned after 190 OS events or 12 months after IA2, whichever oc- curred first. We present results of the final analysis of OS, 12 months after IA2. Methods: A total of 307 pts with MSI-H/dMMR mCRC and ECOG PS 0 or 1 were randomized 1:1 to 1L pembro 200 mg Q3W for up to 2y or investigator’s choice of mFOLFOX6 or FOLFIRI Q2W ± bevacizumab or cetuximab. Treat- ment continued until PD, unacceptable toxicity, pt/investigator decision to withdraw, or completion of 35 cycles (pembro only). Pts receiving chemo could crossover to pembro for up to 35 cycles after con- firmed PD. Primary end points were OS and PFS (RECIST v1.1, central review). Secondary end points included ORR, duration of response (DOR) (RECIST v1.1, central review), and safety. For OS signifi- cance, the p-value had to meet a prespecified a of 0.0246 (one-sided). Sensitivity analyses to adjust for crossover effect were performed. Data cut-off for final analysis was Feb 19, 2021. Results: Median (range) study follow-up was 44.5 mo (36.0-60.3) with pembro vs 44.4 mo (36.2-58.6) with chemo. 56 (36%) pts crossed over from chemo to pembro, with 37 more receiving anti-PD-1/PD-L1 therapies off study (60% effective crossover rate in the ITT). The HR for OS favored pembro vs chemo with a trend to- ward reduction in the risk of death (HR 0.74; 95% CI, 0.53-1.03; P=0.0359; median not reached [NR] vs 36.7 mo); this difference did not reach statistical significance. Sensitivity analysis by the rank- preserving structure failure time model and inverse probability of censoring weighting showed OS HRs of 0.66 (95% CI 0.42-1.04) and 0.77 (95% CI 0.44-1.38), respectively. Pembro vs chemo met the prespecified criteria for PFS superiority at IA2. At final analysis, median PFS was 16.5 mo vs 8.2 mo (HR 0.59; 95% CI, 0.45-0.79), but was not formally tested per analysis plan. Confirmed ORR was 45.1% (20 CR, 49 PR) vs 33.1% (6 CR, 45 PR). Median (range) DOR was NR (2.3+ to 53.5+) vs 10.6 mo (2.8 to 48.3+), respectively. Treatment-related adverse events (TRAEs) occurred in 79.7% vs 98.6% of pts; 21.6% vs 66.4%, respectively, had grade $3 TRAEs. Conclusions: As 1L therapy for pts with MSI-H/dMMR mCRC, pembro vs chemo provides statistically superior PFS with fewer TRAEs, and is associated with a trend toward reduced mortality that did not meet statistical significance likely due to the high crossover rate from chemo to anti-PD1/PD-L1 therapies. Together these data confirm pem- bro as a new standard-of-care in the 1L for pts with MSI-H/dMMR mCRC. Clinical trial information: NCT02563002. Research Sponsor: Merck & Co., Inc. © 2021 by American Society of Clinical Oncology. Visit abstracts.asco.org and search by abstract for disclosure information. GASTROINTESTINAL CANCER—COLORECTAL AND ANAL 3501 Oral Abstract Session The randomized phase II study of FOLFOXIRI plus cetuximab versus FOLFOXIRI plus bevacizumab as the first-line treatment in metastatic colorectal cancer with RAS wild-type tumors: The DEEPER trial (JACCRO CC-13). Akihito Tsuji, Hisatsugu Ohori, Tatsuro Yamaguchi, Masato Matsuura, Atsujiro Nishioka, Akitaka Makiyama, Shingo Noura, Mitsugu Kochi, Tamotsu Sagawa, Masahito Kotaka, Yutaro Kubota, Yu Sunakawa, Takashi Sekikawa, Masato Nakamura, Masahiro Takeuchi, Wataru Ichikawa, Masashi Fujii; Department of Medical Oncology, Kagawa University Hospital, Takamatsu, Japan; Department of Medi- cal Oncology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Japan; Department of Surgery, To- kyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan; Department of Surgery, Kobe City Nishi-Kobe Medical Center, Kobe, Japan; Division of Hematology, Re- spiratory Medicine and Oncology, Saga University Hospital, Saga, Japan; Department of Hematology/ Oncology, Japan Community Healthcare Organization Kyushu Hospital, Kitakyushu, Japan; Department of Surgery, Toyonaka Municipal Hospital, Toyonaka, Japan; Department of Digestive Surgery, Nihon University Itabashi Hospital, Tokyo, Japan; Division of Gastroenterology, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan; Gastrointestinal Cancer Center, Sano Hospital, Kobe, Japan; Division of Medical Oncology, Showa University Hospital, Tokyo, Japan; Department of Clinical Oncolo- gy, St. Marianna University School of Medicine, Kawasaki, CA, Japan; Division of Clinical Oncology, De- partment of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan; Aizawa Comprehensive Cancer Center, Aizawa Hospital, Matsumoto, Japan; Department of Clinical Medicine (Biostatistics), School of Pharmacy, Kitasato University, Tokyo, Japan; Division of Medical Oncology, Showa University Fujigaoka Hospital, Yokohama, Japan; Department of Digestive Surgery, Nihon Uni- versity School of Medicine, Tokyo, Japan Background: Triplet regimens, FOLFOXIRI, combined with bevacizumab (bev) or panitumumab have been shown to be superior in terms of early tumor shrinkage (ETS) and depth of response (DpR) com- pared to doublet combinations in patients with RAS wild-type metastatic colorectal cancer (mCRC), in the TRIBE trial (N Engl J Med 2014) or the VOLFI trial (J Clin Oncol 2019), respectively. There have been few studies which directly compared cetuximab (cet) with bev when combined with triplet regi- men. Therefore, we investigated the efficacy and safety of bev vs. cet in combination with FOLFOXIRI in previously untreated mCRC patients with RAS wild-type tumors. Methods: This trial was a randomized phase II trial to evaluate modified (m)-FOLFOXIRI (irinotecan 150mg/m2, oxaliplatin 85mg/m2, 5-FU 2400mg/m2) plus cet vs. bev as first-line treatment in terms of DpR during the entire course as the pri- mary endpoint in 360 patients with RAS wild-type mCRC. The aim of the trial was to show that median DpR of cet arm was more than 12.5% higher than bev arm, with a power of 85% at a significance level of 0.05. Secondary endpoints included ETS rate at week 8, overall response rate (ORR), progression- free survival (PFS), overall survival (OS), secondary resection rate, and toxicity. Results: A total of 359 patients were enrolled between July 2015 and June 2019. For the full analysis set (median age 65y, 64% male, PS0/1: 91%/9%, left/right primary: 83%/17%), 173 and 175 patients were randomly as- signed to the cet and bev arms, respectively. On the cutoff date of September 2020, the median num- ber of cycles administered was 10 (range, 1-51) for the cet arm and 12 (range, 1-51) for the bev arm. Safety data was already reported at the ASCO GI symposium 2021 (J Clin Oncol 39, 2021 suppl 3; abstr 86). The primary endpoint was met (p =.001); 57.4%（ -15.0~100） for the cet arm versus 46.0% （-0.6~100）for the bev arm. As for primary tumor sidedness, median DpR were 60.3% versus 46.1% (p =.0007) in the left-side and 50.0% versus 41.2% (p =.46) in the right-side. The ETS rate and ORR as the secondary endpoints were 77.8% and 69.1% in the cet arm versus 74.6% and 71.7% in the bev arm, respectively, with no statistical significance. Although the survival data were immature, PFS and OS of both arms were 12.7 months (95%CI 11.5-14.0) and 37.6 months (95%CI 30.8 to 43.0), respectively. Conclusion: The mFOLFOXIRI plus cet has been shown to be significantly superior to the mFOLFOXIRI plus bev in terms of DpR as the primary endpoint in first-line treatment for RAS wild-type mCRC. Clinical trial information: NCT02515734. Clinical trial information: UMIN000018217. Research Sponsor: Merck Biopharma Co., Ltd. © 2021 by American Society of Clinical Oncology. Visit abstracts.asco.org and search by abstract for disclosure information. GASTROINTESTINAL CANCER—COLORECTAL AND ANAL 3502 Oral Abstract Session Randomized study to investigate FOLFOXIRI plus either bevacizumab or cetuximab as first- line treatment of BRAF V600E-mutant mCRC: The phase-II FIRE-4.5 study (AIO KRK-0116).