Cited by 385Pancreatic and Hepatic Oncology ResearchCancer Immunotherapy and BiomarkersCholangiocarcinoma and Gallbladder Cancer Studies

Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial

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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 +29 more·2022·Nature Medicine

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.

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  • CD40 agonists reprogram macrophages to a less immunosuppressive status, leading to CD8 T cell infiltration and conversion from a cold to a hot tumor.

    “CD40 agonists to reprogram macrophages to a less immunosuppressive status, leading to CD8 T cell infiltration that would drive the conversion from a “cold” to a “hot tumor”183”

    From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [183]

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Authors
Padrón, L. J., Maurer, D. M., O’Hara, M. H., O’Reilly, E. M., Wolff, R. A., Wainberg, Z. A., Ko, A. H., Fisher, G., Rahma, O., Lyman, J. P., Cabanski, C. R., Yu, J. X., Pfeiffer, S. M., Spasic, M., Xu, J., Gherardini, P. F., Karakunnel, J., Mick, R., Alanio, C., Byrne, K. T., Hollmann, T. J., Moore, J. S., Jones, D. D., Tognetti, M., Chen, R. O., Yang, X., Salvador, L., Wherry, E. J., Dugan, U., O’Donnell-Tormey, J., Butterfield, L. H., Hubbard-Lucey, V. M., Ibrahim, R., Fairchild, J., Bucktrout, S., LaVallee, T. M., & Vonderheide, R. H.
Affiliations
  • Parker Institute for Cancer Immunotherapy (US)
  • Abramson Cancer Center (US)
  • The University of Texas MD Anderson Cancer Center (US)
  • University of California, Los Angeles (US)
  • University of California, San Francisco (US)
  • Stanford University (US)
  • Dana-Farber Cancer Institute (US)
  • Memorial Sloan Kettering Cancer Center (US)
  • Biognosys (Switzerland) (CH)
  • Personalis (United States) (US)
  • Apexigen (United States) (US)
  • Bristol-Myers Squibb (United States) (US)
  • Cancer Research Institute (US)
Corresponding author
  • Padrón, Lacey J.
  • Vonderheide, Robert H.
Venue
Nature Medicine
Published
2022-06
Volume
28
Issue
6
Pages
1167-1177
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W4282037063
Cited by
384
References
45
Citations by year
2026: 98 · 2025: 88 · 2024: 109 · 2023: 66 · 2022: 23
FWCI
30.11
Type
journal article
Language
en
Open access
Locations
  • Nature Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion, cc-by)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • Cancer Research Institute
  • Bristol-Myers Squibb
  • University of Pennsylvania
  • Memorial Sloan-Kettering Cancer Center
  • Parker Institute for Cancer Immunotherapy
  • National Cancer Institute (P30CA008748)
Topics
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
Keywords
nivolumab, metastatic pancreatic ductal adenocarcinoma, first-line therapy, chemoimmunotherapy, anti-PD-1, gemcitabine, nab-paclitaxel, overall survival, tumor immune microenvironment, peripheral blood T cells, CD4+ T cell infiltration, treatment response biomarkers
MeSH terms
Nivolumab, Albumins, Antibodies, Monoclonal, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Humans, Pancreatic Neoplasms, Carcinoma, Pancreatic Ductal, Tumor Microenvironment

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