CANCERS OF THE ESOPHAGUS AND STOMACH 2 Oral Abstract Session, Thu, 2:15 PM-3:45 PM and Poster Session (Board #D12), Thu, 11:30 AM-1:00 PM and 5:30 PM-6:30 PM Pembrolizumab versus chemotherapy as second-line therapy for advanced esophageal cancer: Phase III KEYNOTE-181 study. Takashi Kojima, Kei Muro, Eric Francois, Chih-Hung Hsu, Toshikazu Moriwaki, Sung-Bae Kim, Se-Hoon Lee, Jaafar Bennouna, Ken Kato, Shen Lin, Shi-Qui Qin, Paula Ferreira, Toshihiko Doi, Antoine Adenis, Peter C. Enzinger, Manish A. Shah, Ruixue Wang, Pooja Bhagia, S. Peter Kang, Jean-Philippe Metges; Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan; Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan; Lacassagne Anticancer Center, Nice, France; National Taiwan University Hospital, Taipei, Taiwan; University of Tsukuba, Tsukuba, Japan; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; University Hospital of Nantes, Nantes, France; Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan; Beijing Cancer Hospital, Beijing, China; PLA Cancer Centre of Nanjing Bayi Hospital, Nanjing, China; Instituto Portuguesˆ de Oncologia Porto, Porto, Portugal; National Cancer Center Hospital East, Chiba, Japan; Centre Oscar Lambret, Lille, France; Dana-Farber Cancer Institute, Boston, MA; Weill Cornell Medicine/ New York Presbyterian Hospital, New York, NY; MSD China, Beijing, China; Merck, Kenilworth, NJ; Merck & Co., Inc., Kenilworth, NJ; Oncology & Haematology Institute, Brest University Hospital, Brest, France Background: Patients with advanced esophageal cancer after first-line chemotherapy (chemo) have a poor prognosis and limited treatment options. We present results of the phase 3 KEYNOTE- 181 study of pembrolizumab vs investigator’s choice chemo as second-line therapy for patients (pts) with advanced/metastatic squamous cell carcinoma (SCC) and adenocarcinoma of the esophagus or Siewert type I adenocarcinoma of the EGJ (NCT02564263). Methods: Eligible pts were randomized 1:1 to pembrolizumab 200 mg Q3W for up to 2 years or investigator’s choice chemo of paclitaxel, docetaxel, or irinotecan. Randomization was stratified by histology (SCC vs adenocarcinoma) and region (Asia vs rest of world). Primary end points were OS in the SCC, PD-L1 combined positive score (CPS) $10, and ITT populations. Results: 628 pts were randomized including 401 with SCC, and 222 with CPS $10. As of October 15, 2018, the median follow-up was 7.1 mo (pembrolizumab) vs 6.9 mo (chemo). Pembrolizumab was superior to chemo for OS in CPS $10 (N=222; median 9.3 vs 6.7 mo; HR 0.69; 95% CI 0.52-0.93; P=0.0074). The 12-mo OS rate in pts with CPS $10 was 43% vs 20%. There was clinically meaningful improvement in OS with pembrolizumab vs chemo in pts with SCC, but this was not statistically significant per prespecified boundaries (N=401; 8.2 mo vs 7.1 mo; HR 0.78; 95% CI 0.63-0.96; P=0.0095). In the ITT population, while directionally favorable, the difference in OS was not statistically significant (N=628; 7.1 mo vs 7.1 mo; HR 0.89; 95% CI 0.75-1.05; P=0.0560). Fewer pts had any-grade (64% vs 86%) or grade 3-5 (18% vs 41%) drug-related AEs with pembrolizumab vs chemo. Conclusion: Pembrolizumab significantly improved OS compared with chemo as second-line therapy for advanced esophageal cancer with PD-L1 CPS $10, with a more favorable safety profile. These data support pembroli- zumab as a new second-line standard of care for esophageal cancer with PD-L1 CPS $10. The phase 3 KEYNOTE-590 study of pembrolizumab plus chemo as first-line therapy for advanced esoph- ageal cancer is ongoing (NCT03189719). Clinical trial information: NCT02564263. © 2019 American Society of Clinical Oncology. Visit gicasym.org and search by abstract for disclosure information. CANCERS OF THE ESOPHAGUS AND STOMACH 3 Oral Abstract Session, Thu, 2:15 PM-3:45 PM and Poster Session (Board #D13), Thu, 11:30 AM-1:00 PM and 5:30 PM-6:30 PM Efficacy and safety of trifluridine/tipiracil (FTD/TPI) in patients (pts) with metastatic gastric cancer (mGC) with or without prior gastrectomy: Results from a phase III study (TAGS). David H. Ilson, Aliaksandr Prokharau, Hendrik-Tobias Arkenau, Michele Ghidini, Kazumasa Fujitani, Eric Van Cutsem, Peter C. Thuss-Patience, Giordano D. Beretta, Wasat Mansoor, Edvard Zhavrid, Maria Alsina, Ben George, Daniel V.T. Catenacci, Robert E. Winkler, Lukas Makris, Toshihiko Doi, Kohei Shitara; Memorial Sloan Kettering Cancer Center, New York, NY; Minsk City Clinical Oncology Dispensary, Minsk, Belarus; Sarah Cannon Research Institute and University College London, London, United Kingdom; Azienda Ospedaliera di Cremona, Cremona, Italy; Osaka General Medical Center, Osaka, Japan; University Hospitals and KU Leuven, Leuven, Belgium; Charit´e – Universit¨atsmedizin Berlin, Berlin, Germany; Humanitas Gavazzeni, Bergamo, Italy; The Christie NHS Foundation Trust Hospital, Manchester, United Kingdom; Alexandrov National Cancer Centre of Belarus, Minsk, Belarus; Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology, Barcelona, Spain; Medical College of Wisconsin, Milwaukee, WI; University of Chicago Medical Center and Biological Sciences, Chicago, IL; Taiho Oncology, Inc., Princeton, NJ; Stathmi, Inc., New Hope, PA; National Cancer Center Hospital East, Chiba, Japan Background: The phase 3 study TAGS demonstrated that the novel oral therapy FTD/TPI (TAS-102) represents an effective treatment option with a manageable safety profile for pts with heavily pretreated mGC. In an earlier single-arm Japanese phase 2 trial in mGC, no differences were found in the pharmacokinetics of either FTD or TPI in pts with or without prior gastrectomy. We evaluated the efficacy and safety of FTD/TPI in pts with or without prior gastrectomy within the TAGS study. Methods: In this global phase 3 study of adult pts with mGC who had received $ 2 prior regimens of chemotherapy, pts were randomized 2:1 to receive FTD/TPI (35 mg/m2 BID on days 1–5 and 8–12 of each 28-day cycle) or placebo, plus best supportive care. We performed a preplanned analysis of efficacy and safety endpoints in pt subgroups with or without prior gastrectomy. Results: Of 507 randomized pts, 221 (44%) had a prior gastrectomy (FTD/TPI, 147/337; placebo, 74/170). Baseline pt characteristics were balanced across pt subgroups. FTD/TPI prolonged survival versus placebo regardless of gastrectomy (table). The frequency of neutropenia/leukopenia appeared to be higher among FTD/TPI-treated pts with vs without gastrectomy, but this did not result in more treatment discontinuations (table). Conclusions: In the TAGS study, subgroup analysis demonstrated that FTD/TPI is an effective treatment option with a manageable safety profile for pts with heavily pretreated mGC, regardless of prior gastrectomy. Clinical trial information: NCT02500043. Gastrectomy No gastrectomy FTD/TPI Placebo FTD/TPI Placebo ITT population, n 147 74 190 96 Median OS (95% CI), mo 6.0 (4.6–7.0) 3.4 (2.7–3.8) 5.6 (4.6–6.2) 3.8 (3.1–5.9) HR (95% CI) 0.57 (0.41–0.79) 0.80 (0.60–1.06) OS rate (95% CI), % 6mo 50 (41–58) 24 (15–35) 44 (37–52) 39 (30–49) 12 mo 20 (12–28) 9 (3–19) 22 (16–30) 16 (8–26) Safety population, n 145 73 190 95 Grade ‡3 AEs of any cause, % Any 84 60 76 56 Most commona Neutropenia 28 0 19 0 Anemia 21 4 17 11 Decreased neutrophil count 17 0 7 0 Leukopenia 10 0 4 0 Fatigue 2 5 11 6 AEs of any grade or cause, % Leading to dosing modification 65 21 53 23 Leading to treatment discontinuation 10 16 15 17 aOccurring in $10% of pts in any group © 2019 American Society of Clinical Oncology. Visit gicasym.org and search by abstract for disclosure information. CANCERS OF THE ESOPHAGUS AND STOMACH 4 Oral Abstract Session, Thu, 2:15 PM-3:45 PM and Poster Session (Board #D14), Thu, 11:30 AM-1:00 PM and 5:30 PM-6:30 PM A phase III, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of andecaliximab combined with mFOLFOX6 as first-line treatment in patients with advanced gastric or gastroesophageal junction adenocarcinoma (GAMMA-1). Manish A. Shah, Eduardo Patricio Yanez Ruiz, Gyorgy Bodoky, Alexander Starodub, David Cunningham, Desmond Yip, Zev A. Wainberg, Johanna C. Bendell, Dung Thai, Pankaj Bhargava, Jaffer A. Ajani; Weill Cornell Medicine/New York Presbyterian Hospital, New York, NY; University de la Frontera, Temuco, Chile; Szent L´aszl´o Teaching Hospital, Budapest, Hungary; Parkview Comprehensive Cancer Institute/Parkview Health, Fort Wayne, IN; The Royal Marsden NHS Foundation Trust, Sutton and London Hospital, Sutton, United Kingdom; ANU Medical School, Australian National University, Canberra, Australia; University of California Los Angeles School of Medicine, Los Angeles, CA; Sarah Cannon Research Institute/ Tennessee Oncology, Nashville, TN; Gilead Sciences, Inc., Foster City, CA; University of Texas MD Anderson Cancer Center, Houston, TX Background: Andecaliximab (ADX) is a monoclonal antibody that inhibits matrix metalloproteinase 9, an extracellular enzyme involved in matrix remodeling, tumor growth, and metastasis. A phase I/Ib study of mFOLFOX6 + ADX revealed encouraging antitumor activity in patients (pts) with gastric or gastroesophageal junction (GEJ) adenocarcinoma (median first-line, progression-free survival [PFS] of 9.9 months). Methods: This phase 3, randomized, double-blind, multicenter study investigated the efficacy and safety of mFOLFOX6 with/without ADX in pts with untreated HER2-negative gastric or GEJ adenocarcinoma. Randomization was 1:1 to mFOLFOX6 + ADX or mFOLFOX6 + placebo (PBO).