Scholarlink

Purpose <p>Survival is poor for patients with recurrent glioblastoma. We prospectively investigated the use of tremelimumab (CTLA-4 inhibitor) and durvalumab (PD-L1 inhibitor) given pre- and post-surgery to assess clinical activity and safety, and to understand the intratumoral immunologic changes. This report focuses on clinical outcomes.</p> Methods <p>Recurrent glioblastoma patients were randomized to either: Arm 1, tremelimumab (75&#xa0;mg every 4 weeks IV); Arm 2, durvalumab (750&#xa0;mg every 2 weeks); or Arm 3, combination (tremelimumab 75&#xa0;mg every 4 weeks for 7 doses then every 12 weeks along with durvalumab 750&#xa0;mg every 2 weeks). Eligible patients received treatment 14 days prior to surgery, then underwent clinically indicated resection, followed by adjuvant treatment starting within 28 days after surgery.</p> Results <p>Thirty-one patients were evaluable. Median OS and PFS for the entire cohort was 8.9 months (95% CI, 7.5–14.2) and 3.2 months (95% CI, 3.0-4.1), respectively. Median OS for Arm 1 was 7.5 months (95% CI, 2.3–14.7), 13.2 for Arm 2 (95% CI, 2.6–28.0), and 7.9 (95% CI, 4.8–14.2; <i>P</i> = 0.33) for Arm 3. Treatment was well tolerated. One patient developed grade 3 colitis while 2 patients had grade 2 dermatitis. Ten patients had grade 3 hypertension, 4 patients had grade 3 hyperglycemia, and 2 patients had wound complications. There were no treatment related deaths or severe immune related toxicities.</p> Conclusion <p>The combination of tremelimumab and durvalumab is safe in recurrent glioblastoma though there was no statistical improvement in survival. This data aligns with prior studies showing a lack of benefit with checkpoint inhibitors.</p> Trail registration <p>ClinicalTrials.Gov Registration NCT02794883. Registration Date 6/9/2016.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A phase 2, open label, clinical trial of pre-surgical and adjuvant treatment of recurrent glioblastoma with tremelimumab and durvalumab alone and in combination

  • 期刊论文

  • 发表日期：

    2026年1月28日

查看全文
  • Karan S. Dixit,
  • Priya Kumthekar,
  • Rimas V. Lukas,
  • Andrew Williams,
  • Matthew C. Tate,
  • James P. Chandler,
  • Pouya Jamshidi,
  • Irene Helenowski,
  • Hui Zhang,
  • Orin Bloch,
  • Jeffrey J. Raizer

摘要

Purpose

Survival is poor for patients with recurrent glioblastoma. We prospectively investigated the use of tremelimumab (CTLA-4 inhibitor) and durvalumab (PD-L1 inhibitor) given pre- and post-surgery to assess clinical activity and safety, and to understand the intratumoral immunologic changes. This report focuses on clinical outcomes.

Methods

Recurrent glioblastoma patients were randomized to either: Arm 1, tremelimumab (75 mg every 4 weeks IV); Arm 2, durvalumab (750 mg every 2 weeks); or Arm 3, combination (tremelimumab 75 mg every 4 weeks for 7 doses then every 12 weeks along with durvalumab 750 mg every 2 weeks). Eligible patients received treatment 14 days prior to surgery, then underwent clinically indicated resection, followed by adjuvant treatment starting within 28 days after surgery.

Results

Thirty-one patients were evaluable. Median OS and PFS for the entire cohort was 8.9 months (95% CI, 7.5–14.2) and 3.2 months (95% CI, 3.0-4.1), respectively. Median OS for Arm 1 was 7.5 months (95% CI, 2.3–14.7), 13.2 for Arm 2 (95% CI, 2.6–28.0), and 7.9 (95% CI, 4.8–14.2; P = 0.33) for Arm 3. Treatment was well tolerated. One patient developed grade 3 colitis while 2 patients had grade 2 dermatitis. Ten patients had grade 3 hypertension, 4 patients had grade 3 hyperglycemia, and 2 patients had wound complications. There were no treatment related deaths or severe immune related toxicities.

Conclusion

The combination of tremelimumab and durvalumab is safe in recurrent glioblastoma though there was no statistical improvement in survival. This data aligns with prior studies showing a lack of benefit with checkpoint inhibitors.

Trail registration

ClinicalTrials.Gov Registration NCT02794883. Registration Date 6/9/2016.