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<p>This single-arm phase II trial (ACTRN12620000918921) evaluated the clinical activity of tremelimumab (10 mg/kg intravenously every 4 weeks for 6 cycles) in advanced cancers with a high tumour mutational burden (TMB), defined as TMB &gt; 10 mutations/megabase (mut/Mb) on standard platforms (TSO500 panel, F1CDx), or &gt;20 mut/Mb on the TST170 panel. The primary objective was 6-month progression-free survival rate (PFS6) by iRECIST. Secondary objectives included objective response; the ratio of time to progression (TTP) on study to TTP on prior therapy (TTP2:TTP1); overall survival (OS); and safety. After minimum followup of 12 months, the PFS6 was 6% (95% CI 0–24%), with a median PFS and OS of 1.9 (95% CI 1.4–2.8) and 6.3 (2.8–10.3) months, respectively. Amongst 19 evaluable patients, two partial responses occurred in an endometrial adenocarcinoma and an undifferentiated pleomorphic sarcoma, maintained for 3.8 and 15.9 months respectively, both with TMB &gt;20 mut/Mb. Adverse events were experienced by 19 patients (90%), with 15 patients (72%) experiencing grade 3–5 adverse events. Seven tremelimumab-related serious adverse events (grade 2–3) occurred in 5 patients. While the primary PFS6 endpoint was not met, there were two durable objective responses in rare cancers and a favourable change in disease trajectory for an additional five patients based on TTP ratio <InlineEquation ID="IEq1"> <EquationSource Format="TEX">\(\ge\)</EquationSource> <EquationSource Format="MATHML"><math> <mo>≥</mo> </math></EquationSource> </InlineEquation>1.3.</p>

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A signal-seeking phase 2 study of tremelimumab in advanced cancers with high tumour mutational burden

  • 期刊论文

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  • 发表日期：

    2025年11月21日

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  • Subotheni Thavaneswaran,
  • Frank Lin,
  • David Espinoza,
  • John Grady,
  • Peey-Sei Kok,
  • Sarah Chinchen,
  • Nick Pavlakis,
  • Vladimir Andelkovic,
  • Michail Charakidis,
  • Paul Craft,
  • Michael Brown,
  • Jayesh Desai,
  • Peter Lau,
  • Maya Kansara,
  • John Simes,
  • David Thomas

摘要

This single-arm phase II trial (ACTRN12620000918921) evaluated the clinical activity of tremelimumab (10 mg/kg intravenously every 4 weeks for 6 cycles) in advanced cancers with a high tumour mutational burden (TMB), defined as TMB > 10 mutations/megabase (mut/Mb) on standard platforms (TSO500 panel, F1CDx), or >20 mut/Mb on the TST170 panel. The primary objective was 6-month progression-free survival rate (PFS6) by iRECIST. Secondary objectives included objective response; the ratio of time to progression (TTP) on study to TTP on prior therapy (TTP2:TTP1); overall survival (OS); and safety. After minimum followup of 12 months, the PFS6 was 6% (95% CI 0–24%), with a median PFS and OS of 1.9 (95% CI 1.4–2.8) and 6.3 (2.8–10.3) months, respectively. Amongst 19 evaluable patients, two partial responses occurred in an endometrial adenocarcinoma and an undifferentiated pleomorphic sarcoma, maintained for 3.8 and 15.9 months respectively, both with TMB >20 mut/Mb. Adverse events were experienced by 19 patients (90%), with 15 patients (72%) experiencing grade 3–5 adverse events. Seven tremelimumab-related serious adverse events (grade 2–3) occurred in 5 patients. While the primary PFS6 endpoint was not met, there were two durable objective responses in rare cancers and a favourable change in disease trajectory for an additional five patients based on TTP ratio \(\ge\) ≥ 1.3.