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<p>We report long-term clinical and immunologic outcomes from the MM1636 trial (NCT03047928), which evaluated a peptide vaccine targeting IDO and PD-L1 in combination with nivolumab in patients with advanced melanoma. At a five-year follow-up, the combination demonstrated durable clinical efficacy, with a 25.5-month median progression-free survival. Serum proteomic profiling identified vaccine-specific immune signatures, with increase in CCL3, CCL4, and TNFα emerging as biomarkers of long progression-free survival. Increase in these markers were not observed in a matched anti-PD-1 monotherapy cohort, suggesting distinct immune modulation by the vaccine. Functional studies confirmed vaccine-induced targeting of myeloid cells and associated increase in these cytokines. These findings provide evidence for durable benefit from immune modulatory vaccination and nominate CCL3, CCL4, and TNFα as candidate biomarkers for response.</p>

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Five-year clinical outcome and immune biomarkers of durable response from the MM1636 trial on IDO/PD-L1 vaccination and PD-1 blockade in first line metastatic melanoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月14日

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  • Sidsel Pedersen,
  • Mikkel Byrdal,
  • Evelina Martinenaite,
  • Cathrine Lund Lorentzen,
  • Julie Westerlin Kjeldsen,
  • Steffen Ullitz Thorsen,
  • Anders Kverneland,
  • Mai-Britt Zocca,
  • Mads Hald Andersen,
  • Inge Marie Svane

摘要

We report long-term clinical and immunologic outcomes from the MM1636 trial (NCT03047928), which evaluated a peptide vaccine targeting IDO and PD-L1 in combination with nivolumab in patients with advanced melanoma. At a five-year follow-up, the combination demonstrated durable clinical efficacy, with a 25.5-month median progression-free survival. Serum proteomic profiling identified vaccine-specific immune signatures, with increase in CCL3, CCL4, and TNFα emerging as biomarkers of long progression-free survival. Increase in these markers were not observed in a matched anti-PD-1 monotherapy cohort, suggesting distinct immune modulation by the vaccine. Functional studies confirmed vaccine-induced targeting of myeloid cells and associated increase in these cytokines. These findings provide evidence for durable benefit from immune modulatory vaccination and nominate CCL3, CCL4, and TNFα as candidate biomarkers for response.