美国宾夕法尼亚大学Robert H. Vonderheide研究小组完成sotigalimab和/或nivolumab与化疗用于一线转移性胰腺癌治疗的临床试验。相关论文于2022年6月3日在线发表于国际学术期刊《自然—医学》。

Author: Padrn, Lacey J., Maurer, Deena M., OHara, Mark H., OReilly, Eileen M., Wolff, Robert A., Wainberg, Zev A., Ko, Andrew H., Fisher, George, Rahma, Osama, Lyman, Jaclyn P., Cabanski, Christopher R., Yu, Jia Xin, Pfeiffer, Shannon M., Spasic, Marko, Xu, Jingying, Gherardini, Pier Federico, Karakunnel, Joyson, Mick, Rosemarie, Alanio, Ccile, Byrne, Katelyn T., Hollmann, Travis J., Moore, Jonni S., Jones, Derek D., Tognetti, Marco, Chen, Richard O., Yang, Xiaodong, Salvador, Lisa, Wherry, E. John, Dugan, Ute, ODonnell-Tormey, Jill, Butterfield, Lisa H., Hubbard-Lucey, Vanessa M., Ibrahim, Ramy, Fairchild, Justin, Bucktrout, Samantha, LaVallee, Theresa M., Vonderheide, Robert H.

Issue&Volume: 2022-06-03

Abstract: Chemotherapy combined with immunotherapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for pancreatic ductal adenocarcinoma (PDAC). We conducted a randomized phase 2 trial evaluating the efficacy of nivolumab (nivo; anti-PD-1) and/or sotigalimab (sotiga; CD40 agonistic antibody) with gemcitabine/nab-paclitaxel (chemotherapy) in patients with first-line metastatic PDAC (NCT03214250). In 105 patients analyzed for efficacy, the primary endpoint of 1-year overall survival (OS) was met for nivo/chemo (57.7%, P=0.006 compared to historical 1-year OS of 35%, n=34) but was not met for sotiga/chemo (48.1%, P=0.062, n=36) or sotiga/nivo/chemo (41.3%, P=0.223, n=35). Secondary endpoints were progression-free survival, objective response rate, disease control rate, duration of response and safety. Treatment-related adverse event rates were similar across arms. Multi-omic circulating and tumor biomarker analyses identified distinct immune signatures associated with survival for nivo/chemo and sotiga/chemo. Survival after nivo/chemo correlated with a less suppressive tumor microenvironment and higher numbers of activated, antigen-experienced circulating T cells at baseline. Survival after sotiga/chemo correlated with greater intratumoral CD4 T cell infiltration and circulating differentiated CD4 T cells and antigen-presenting cells. A patient subset benefitting from sotiga/nivo/chemo was not identified. Collectively, these analyses suggest potential treatment-specific correlates of efficacy and may enable biomarker-selected patient populations in subsequent PDAC chemoimmunotherapy trials.

DOI: 10.1038/s41591-022-01829-9

Source: https://www.nature.com/articles/s41591-022-01829-9