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<p>Lymphocyte activation gene 3 (LAG-3) is an immune checkpoint implicated in T cell exhaustion and a potential therapeutic target in glioblastoma (GBM). We conducted a multicenter, open-label, phase 1 study with sequential allocation to evaluate the safety and preliminary activity of the anti-LAG-3 antibody relatlimab, administered alone or with the anti-programmed cell death protein 1 (PD-1) antibody nivolumab, in patients with recurrent GBM. Forty-six patients were treated (23 per cohort). The primary endpoint of safety was met, with maximum tolerated doses of 800 mg relatlimab for monotherapy and 160 mg relatlimab/240 mg nivolumab for combination therapy. Treatment-related grade 3–4 adverse events occurred in 6 of 23 patients receiving combination therapy and were not observed with monotherapy. Neoadjuvant administration was associated with increased intratumoral CD8<sup>+</sup> T cell infiltration for both monotherapy and combination therapy. Exploratory analyses suggested that tumors with elevated baseline interferon signaling and increased T cell clonality were enriched among patients with durable responses to combination therapy. Twelve-month overall survival was 34.8% with relatlimab alone and 52.2% with combination therapy; however, this study was not designed to assess efficacy. These findings demonstrate an acceptable safety profile and provide preliminary immunologic and clinical signals supporting further evaluation of LAG-3 blockade in GBM. ClinicalTrials.gov identifier: <a href="http://clinicaltrials.gov/study/NCT02658981">NCT02658981</a>.</p>

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Anti-LAG-3 with or without anti-PD-1 in recurrent glioblastoma: a phase 1 trial

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月10日

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  • Michael Lim,
  • Xiaobu Ye,
  • Anna F. Piotrowski,
  • Arati Desai,
  • Manmeet S. Ahluwalia,
  • Tobias Walbert,
  • Glenn Lesser,
  • Benjamin M. Ellingson,
  • David M. Peereboom,
  • Joy D. Fisher,
  • Serena Desideri,
  • Christina Jackson,
  • Ayush Pant,
  • Aanchal Jain,
  • Rohit Verma,
  • Benjamin Oberlton,
  • Hadeesha Piyadasa,
  • Chetan Bettegowda,
  • Logan Engle,
  • Janis Taube,
  • Sean C. Bendall,
  • John Choi,
  • Jan Drappatz,
  • Frank S. Lieberman,
  • Lawrence R. Kleinberg,
  • Drew M. Pardoll,
  • Louis B. Nabors,
  • Patrick Y. Wen,
  • Stuart A. Grossman

摘要

Lymphocyte activation gene 3 (LAG-3) is an immune checkpoint implicated in T cell exhaustion and a potential therapeutic target in glioblastoma (GBM). We conducted a multicenter, open-label, phase 1 study with sequential allocation to evaluate the safety and preliminary activity of the anti-LAG-3 antibody relatlimab, administered alone or with the anti-programmed cell death protein 1 (PD-1) antibody nivolumab, in patients with recurrent GBM. Forty-six patients were treated (23 per cohort). The primary endpoint of safety was met, with maximum tolerated doses of 800 mg relatlimab for monotherapy and 160 mg relatlimab/240 mg nivolumab for combination therapy. Treatment-related grade 3–4 adverse events occurred in 6 of 23 patients receiving combination therapy and were not observed with monotherapy. Neoadjuvant administration was associated with increased intratumoral CD8+ T cell infiltration for both monotherapy and combination therapy. Exploratory analyses suggested that tumors with elevated baseline interferon signaling and increased T cell clonality were enriched among patients with durable responses to combination therapy. Twelve-month overall survival was 34.8% with relatlimab alone and 52.2% with combination therapy; however, this study was not designed to assess efficacy. These findings demonstrate an acceptable safety profile and provide preliminary immunologic and clinical signals supporting further evaluation of LAG-3 blockade in GBM. ClinicalTrials.gov identifier: NCT02658981.