BMC Cancer (Feb 2023)

Safety and efficacy of Pucotenlimab (HX008) - a humanized immunoglobulin G4 monoclonal antibody in patients with locally advanced or metastatic melanoma: a single-arm, multicenter, phase II study

  • Chuanliang Cui,
  • Yu Chen,
  • Zhiguo Luo,
  • Zhengyun Zou,
  • Yu Jiang,
  • Hongming Pan,
  • Qingxia Fan,
  • Jianfu Zhao,
  • Qing Xu,
  • Renbing Jiang,
  • Xuan Wang,
  • Taiyang Ma,
  • Zhen Guo,
  • Lu Si,
  • Zhihong Chi,
  • Xinan Sheng,
  • Yiwei Dou,
  • Qian Tan,
  • Di Wu,
  • Jun Guo

DOI
https://doi.org/10.1186/s12885-022-10473-y
Journal volume & issue
Vol. 23, no. 1
pp. 1 – 11

Abstract

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Abstract Background Pucotenlimab is a novel recombinant humanized anti-PD-1 (Programmed death-1) monoclonal antibody, which belongs to the human IgG4/kappa subtype, and can selectively block the binding of PD-1 with its ligands PD-L1 and PD-L2. Methods In this phase 2 trial, patients with locally advanced or metastatic melanoma who had failed conventional treatment (chemotherapy, targeted therapy, interferon, IL-2, et al.) were recruited. The patients were administrated with Pucotenlimab of 3 mg/kg every 3 weeks until disease progression, intolerable toxicity, or treatment discontinuation for any other reasons. The primary endpoint was the overall response rate (ORR). The secondary endpoints were disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and toxicity. Results One-hundred and nineteen patients were enrolled and followed up for 19.32 (ranging from 15.901 to 24.608) months by the cutoff date of July 30th, 2021. The ORR was 20.17% (24/119, 95% CI, 13.370%-28.506%) based on both independent review committee (IRC) and the investigator’s assessment per RECIST v1.1. The median PFS were 2.89 (95% CI, 2.037–4.074) months and 2.46 (95% CI, 2.004–4.008) months based on IRC and investigator’s assessment, respectively, per RECIST v1.1. The median OS was 16.59 (95% CI, 13.963–26.973) months. Treatment-related adverse events (TRAEs) occurred in 77.3% (92/119) of the patients. The incidence of Grade ≥ 3 TRAEs was 15.1% (18/119). In addition, none of the patients died because of TRAEs. As for biomarker analysis, Eotaxin (CCL11) and MCP-1 (CCL2) were related to treatment response, while TNF-α and VEGF were related to treatment failure. Conclusions Pucotenlimab as a ≥ 2nd line therapy showed promising efficacy and tolerable toxicity for patients with locally advanced or metastatic melanoma. Trial registration Clinicaltrials.gov Identifier: NCT04749485 (registered retrospectively on 11/02/2021).

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