Efficacy and Safety of Serplulimab Combined With Chemotherapy as Neoadjuvant Treatment for Locally Advanced Gastric Cancer or Adenocarcinoma of Esophagogastric Junction

Summary

This is a multicenter, double-blind, randomized, phase 2 trial to investigate the efficacy and safety of serlulimab combined with nab-paclitaxel plus SOX versus nab-paclitaxel plus SOX alone as neoadjuvant treatment for locally advanced GC or AEG. The goal of this clinical trial is to learn if serlulimab combined with nab-paclitaxel plus SOX as neoadjuvant treatment for locally advanced AEG/GC. It will also learn about the safety of serlulimab combined with nab-paclitaxel plus SOX. The main questions it aims to answer are: Does serlulimab increase the pCR of participants with locally advanced AEG/GC ? What medical problems do participants have when taking serlulimab? Researchers will compare to a placebo (a look-alike substance that contains no drug) to see if serlulimab combined with nab-paclitaxel plus SOX as neoadjuvant treatment for locally advanced AEG/GC. Participants will: Eligible patients were randomly assigned to receive serlulimab (4.5 mg intravenously on day 1) combined with chemotherapy (nap-paclitaxel 260 mg/m2 intravenously on days 1, OXA 130mg/ /m2, intravenously on days 1, and S-1 40 to 60 mg orally twice daily depending on BSA on days 1 to 14) or chemotherapy alone every 3 weeks for 3 preoperative cycles followed by 3 postoperative cycles. All patients will be followed for survival.

Timeline

Start

2024-11-15

Primary completion

2026-05-31

Completion

2026-09-30

Publications

• Results Van Cutsem E, Sagaert X, Topal B, Haustermans K, Prenen H. Gastric cancer. Lancet. 2016 Nov 26;388(10060):2654-2664. doi: 10.1016/S0140-6736(16)30354-3. Epub 2016 May 5.
• Results Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32. doi: 10.3322/caac.21338. Epub 2016 Jan 25.
• Results Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev. 2014 May;23(5):700-13. doi: 10.1158/1055-9965.EPI-13-1057. Epub 2014 Mar 11.
• Results Murakami TT, Scranton RA, Brown HE, Harris RB, Chen Z, Musuku S, Oren E. Management of Helicobacter Pylori in the United States: Results from a national survey of gastroenterology physicians. Prev Med. 2017 Jul;100:216-222. doi: 10.1016/j.ypmed.2017.04.021. Epub 2017 Apr 27.
• Results Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N, Schlemper RJ. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001 Sep 13;345(11):784-9. doi: 10.1056/NEJMoa001999.
• Results Plummer M, Franceschi S, Vignat J, Forman D, de Martel C. Global burden of gastric cancer attributable to Helicobacter pylori. Int J Cancer. 2015 Jan 15;136(2):487-90. doi: 10.1002/ijc.28999. Epub 2014 Jun 11.
• Results Brar S, Law C, McLeod R, Helyer L, Swallow C, Paszat L, Seevaratnam R, Cardoso R, Dixon M, Mahar A, Lourenco LG, Yohanathan L, Bocicariu A, Bekaii-Saab T, Chau I, Church N, Coit D, Crane CH, Earle C, Mansfield P, Marcon N, Miner T, Noh SH, Porter G, Posner MC, Prachand V, Sano T, van de Velde C, Wong S, Coburn N; International multidisciplinary expert panel. Defining surgical quality in gastric cancer: a RAND/UCLA appropriateness study. J Am Coll Surg. 2013 Aug;217(2):347-57.e1. doi: 10.1016/j.jamcollsurg.2013.01.067. Epub 2013 May 8. No abstract available.
• Results Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. Lancet. 2020 Aug 29;396(10251):635-648. doi: 10.1016/S0140-6736(20)31288-5.
• Results Li Z, Shan F, Wang Y, Zhang Y, Zhang L, Li S, Jia Y, Xue K, Miao R, Li Z, Ji J. Correlation of pathological complete response with survival after neoadjuvant chemotherapy in gastric or gastroesophageal junction cancer treated with radical surgery: A meta-analysis. PLoS One. 2018 Jan 25;13(1):e0189294. doi: 10.1371/journal.pone.0189294. eCollection 2018.
• Results Ychou M, Boige V, Pignon JP, Conroy T, Bouche O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Geneve J, Lasser P, Rougier P. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. doi: 10.1200/JCO.2010.33.0597. Epub 2011 Mar 28.
• Results Sumpter K, Harper-Wynne C, Cunningham D, Rao S, Tebbutt N, Norman AR, Ward C, Iveson T, Nicolson M, Hickish T, Hill M, Oates J. Report of two protocol planned interim analyses in a randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer receiving ECF. Br J Cancer. 2005 Jun 6;92(11):1976-83. doi: 10.1038/sj.bjc.6602572.
• Results Li ZY, Koh CE, Bu ZD, Wu AW, Zhang LH, Wu XJ, Wu Q, Zong XL, Ren H, Tang L, Zhang XP, Li JY, Hu Y, Shen L, Ji JF. Neoadjuvant chemotherapy with FOLFOX: improved outcomes in Chinese patients with locally advanced gastric cancer. J Surg Oncol. 2012 Jun 15;105(8):793-9. doi: 10.1002/jso.23009. Epub 2011 Dec 20.
• Results Kochi M, Fujii M, Kanamori N, Mihara Y, Funada T, Tamegai H, Watanabe M, Takayama Y, Suda H, Takayama T. Phase II Study of Neoadjuvant Chemotherapy With S-1 and CDDP in Patients With Lymph Node Metastatic Stage II or III Gastric Cancer. Am J Clin Oncol. 2017 Feb;40(1):17-21. doi: 10.1097/COC.0000000000000058.
• Results Li T, Chen L. [Efficacy and safety of SOX regimen as neoadjuvant chemotherapy for advanced gastric cancer]. Zhonghua Wei Chang Wai Ke Za Zhi. 2011 Feb;14(2):104-6. Chinese.
• Results Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999 Dec;5(12):1365-9. doi: 10.1038/70932.
• Results Lote H, Cafferkey C, Chau I. PD-1 and PD-L1 blockade in gastrointestinal malignancies. Cancer Treat Rev. 2015 Dec;41(10):893-903. doi: 10.1016/j.ctrv.2015.09.004. Epub 2015 Sep 21.
• Results Sun S, Fei X, Mao Y, Wang X, Garfield DH, Huang O, Wang J, Yuan F, Sun L, Yu Q, Jin X, Wang J, Shen K. PD-1(+) immune cell infiltration inversely correlates with survival of operable breast cancer patients. Cancer Immunol Immunother. 2014 Apr;63(4):395-406. doi: 10.1007/s00262-014-1519-x. Epub 2014 Feb 11.
• Results Hawkes EA, Grigg A, Chong G. Programmed cell death-1 inhibition in lymphoma. Lancet Oncol. 2015 May;16(5):e234-45. doi: 10.1016/S1470-2045(15)70103-8.
• Results Boku N, Ryu MH, Kato K, Chung HC, Minashi K, Lee KW, Cho H, Kang WK, Komatsu Y, Tsuda M, Yamaguchi K, Hara H, Fumita S, Azuma M, Chen LT, Kang YK. Safety and efficacy of nivolumab in combination with S-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: interim results of a randomized, phase II trial (ATTRACTION-4). Ann Oncol. 2019 Feb 1;30(2):250-258. doi: 10.1093/annonc/mdy540.
• Results Bang YJ, Kang YK, Catenacci DV, Muro K, Fuchs CS, Geva R, Hara H, Golan T, Garrido M, Jalal SI, Borg C, Doi T, Yoon HH, Savage MJ, Wang J, Dalal RP, Shah S, Wainberg ZA, Chung HC. Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study. Gastric Cancer. 2019 Jul;22(4):828-837. doi: 10.1007/s10120-018-00909-5. Epub 2019 Mar 25.
• Results Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017 Jan 18;541(7637):321-330. doi: 10.1038/nature21349.
• Results Zheng C, Zheng L, Yoo JK, Guo H, Zhang Y, Guo X, Kang B, Hu R, Huang JY, Zhang Q, Liu Z, Dong M, Hu X, Ouyang W, Peng J, Zhang Z. Landscape of Infiltrating T Cells in Liver Cancer Revealed by Single-Cell Sequencing. Cell. 2017 Jun 15;169(7):1342-1356.e16. doi: 10.1016/j.cell.2017.05.035.
• Results Azizi E, Carr AJ, Plitas G, Cornish AE, Konopacki C, Prabhakaran S, Nainys J, Wu K, Kiseliovas V, Setty M, Choi K, Fromme RM, Dao P, McKenney PT, Wasti RC, Kadaveru K, Mazutis L, Rudensky AY, Pe'er D. Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment. Cell. 2018 Aug 23;174(5):1293-1308.e36. doi: 10.1016/j.cell.2018.05.060. Epub 2018 Jun 28.
• Results Zhang L, Yu X, Zheng L, Zhang Y, Li Y, Fang Q, Gao R, Kang B, Zhang Q, Huang JY, Konno H, Guo X, Ye Y, Gao S, Wang S, Hu X, Ren X, Shen Z, Ouyang W, Zhang Z. Lineage tracking reveals dynamic relationships of T cells in colorectal cancer. Nature. 2018 Dec;564(7735):268-272. doi: 10.1038/s41586-018-0694-x. Epub 2018 Oct 29.

Drugs

Indications