1. Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial
- Author
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Padrón, Lacey J, Maurer, Deena M, O’Hara, Mark H, O’Reilly, 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, Cécile, 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, O’Donnell-Tormey, Jill, Butterfield, Lisa H, Hubbard-Lucey, Vanessa M, Ibrahim, Ramy, Fairchild, Justin, Bucktrout, Samantha, LaVallee, Theresa M, and Vonderheide, Robert H
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Pancreatic Cancer ,Clinical Trials and Supportive Activities ,Cancer ,Orphan Drug ,Clinical Research ,Rare Diseases ,Digestive Diseases ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Good Health and Well Being ,Albumins ,Antibodies ,Monoclonal ,Antineoplastic Agents ,Antineoplastic Combined Chemotherapy Protocols ,Carcinoma ,Pancreatic Ductal ,Humans ,Nivolumab ,Pancreatic Neoplasms ,Tumor Microenvironment ,Medical and Health Sciences ,Biomedical and clinical sciences ,Health sciences - 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.
- Published
- 2022