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Background <p>This study assessed the safety, preliminary antitumor activity, and pharmacokinetics of HR070803 (a novel liposomal irinotecan) in combination with 5-FU/LV and oxaliplatin for treatment-naive patients with unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC).</p> Methods <p>This multicenter, open-label, single-arm, dose-escalation phase 1 study recruited treatment-naive patients aged 18–70 years with unresectable locally advanced or metastatic PDAC. Treatment doses were escalated from 40/60 (HR070803 40 mg/m<sup>2</sup> plus 5-FU/LV and oxaliplatin 60 mg/m<sup>2</sup>) to 60/60 and 60/85. The primary endpoints were maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D). Secondary endpoints included safety, preliminary antitumor activity, and pharmacokinetics.</p> Results <p>A total of 41 patients were enrolled, including 6, 17, and 18 patients in the 40/60, 60/60, and 60/85 group, respectively. Only one patient in the 60/60 group experienced dose-limiting toxicities of grade 3 increased alanine aminotransferase and grade 3 increased aspartate aminotransferase, and the MTD was not reached. Adverse events of grade ≥ 3 were reported in 31 (75.6%) patients, with the most common being decreased neutrophil count and increased gamma-glutamyltransferase. No treatment discontinuation occurred owing to adverse events, and there were no treatment-related deaths. The overall response (complete or partial response) rate was 29.3% in the total population. Pharmacokinetic results demonstrated prolonged circulation and slow release of free irinotecan.</p> Conclusions <p>HR070803 plus 5-FU/LV and oxaliplatin demonstrated an acceptable toxicity, good antitumor activity, and favorable pharmacokinetic profile as a first-line treatment for patients with unresectable locally advanced or metastatic PDAC. Based on the comprehensive data obtained during the dose escalation and dose expansion stages, HR070803 60 mg/m<sup>2</sup> plus 5-FU/LV and oxaliplatin 85 mg/m<sup>2</sup> was chosen as the RP2D.</p> Trial registration <p>Clinical trials.gov NCT04796948; registered March 15, 2021.</p>

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Phase 1 trial of HR070803 (an Irinotecan liposome) in combination with 5-fluorouracil, leucovorin, and oxaliplatin for untreated advanced or metastatic pancreatic ductal adenocarcinoma

  • 期刊论文

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  • 发表日期：

    2025年7月7日

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  • Qiang Xu,
  • Xue Zhao,
  • Xianze Wang,
  • Ruizhe Zhu,
  • Yuejuan Cheng,
  • Tao Xia,
  • Heshui Wu,
  • He Tian,
  • Yuping Sun,
  • Mingjun Zhang,
  • Chuntao Gao,
  • Deliang Fu,
  • Xiaojie Wu,
  • Tongsen Zheng,
  • Xiaoyu Yin,
  • Yili Chen,
  • Xiaobing Chen,
  • Zhihua Li,
  • Rufu Chen,
  • Xue Yang,
  • Huan Wang,
  • Quanren Wang,
  • Xiaohong Han,
  • Wenming Wu

摘要

Background

This study assessed the safety, preliminary antitumor activity, and pharmacokinetics of HR070803 (a novel liposomal irinotecan) in combination with 5-FU/LV and oxaliplatin for treatment-naive patients with unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC).

Methods

This multicenter, open-label, single-arm, dose-escalation phase 1 study recruited treatment-naive patients aged 18–70 years with unresectable locally advanced or metastatic PDAC. Treatment doses were escalated from 40/60 (HR070803 40 mg/m2 plus 5-FU/LV and oxaliplatin 60 mg/m2) to 60/60 and 60/85. The primary endpoints were maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D). Secondary endpoints included safety, preliminary antitumor activity, and pharmacokinetics.

Results

A total of 41 patients were enrolled, including 6, 17, and 18 patients in the 40/60, 60/60, and 60/85 group, respectively. Only one patient in the 60/60 group experienced dose-limiting toxicities of grade 3 increased alanine aminotransferase and grade 3 increased aspartate aminotransferase, and the MTD was not reached. Adverse events of grade ≥ 3 were reported in 31 (75.6%) patients, with the most common being decreased neutrophil count and increased gamma-glutamyltransferase. No treatment discontinuation occurred owing to adverse events, and there were no treatment-related deaths. The overall response (complete or partial response) rate was 29.3% in the total population. Pharmacokinetic results demonstrated prolonged circulation and slow release of free irinotecan.

Conclusions

HR070803 plus 5-FU/LV and oxaliplatin demonstrated an acceptable toxicity, good antitumor activity, and favorable pharmacokinetic profile as a first-line treatment for patients with unresectable locally advanced or metastatic PDAC. Based on the comprehensive data obtained during the dose escalation and dose expansion stages, HR070803 60 mg/m2 plus 5-FU/LV and oxaliplatin 85 mg/m2 was chosen as the RP2D.

Trial registration

Clinical trials.gov NCT04796948; registered March 15, 2021.