Scholarlink

Background <p>This first-in-human phase 1 study (NCT04432597) evaluated the safety and recommended phase 2 dose (RP2D) of PRGN-2009, a gorilla adenoviral-vector targeting oncoproteins E6, E7 (human papillomavirus (HPV)16/18) and E5 (HPV16), as monotherapy (Arm 1A) and combined with the bifunctional TGF-β “trap”/anti-PD-L1 fusion protein bintrafusp alfa (BA; Arm 1B), in patients with recurrent/metastatic HPV-associated cancer.</p> Methods <p>Patients with ≥ 1 prior treatment (immunotherapy allowed) received PRGN-2009 (1 × 10<sup>11</sup> particle units or 5 × 10<sup>11</sup> particle units, subcutaneously) every 2&#xa0;weeks for 3 doses, then every 4&#xa0;weeks (Arm 1A), or PRGN-2009 (RP2D, schedule per Arm 1A) and BA (1200&#xa0;mg, intravenously) every 2&#xa0;weeks (Arm 1B). Primary endpoints were safety and RP2D of PRGN-2009; secondary objectives included overall response rate (ORR) and overall survival (OS).</p> Results <p>Seventeen patients were treated. In Arm 1A (n = 6) there were no dose limiting toxicities or grade 3/4 treatment-related adverse events (TRAEs), 5 × 10<sup>11</sup> PU was selected as RP2D, no responses were observed, and median OS (mOS) was 7.4&#xa0;months (95% CI 2.9–26.8). In Arm 1B (n = 11), grade 3/4 TRAEs occurred in 27% of patients, ORR was 20% for all patients (22% in checkpoint-resistant patients), and mOS was 24.6&#xa0;months (95% CI 9.6-not reached). Multifunctional HPV-specific T cells were increased or induced de novo in 80% of patients and not impacted by anti-vector antibodies. Higher serum IL-8 at baseline associated with shorter OS.</p> Conclusions <p>PRGN-2009 was well tolerated, and immune responses were observed to PRGN-2009. Encouraging anti-tumor activity and OS were noted in the combination with BA arm, consisting mainly of checkpoint-resistant patients.</p> <p><i>Trial Registration</i> ClinicalTrials.gov Identifier: NCT04432597.</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

PRGN-2009 and bintrafusp alfa for patients with advanced or metastatic human papillomavirus-associated cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月21日

查看全文
  • Charalampos S. Floudas,
  • Meghali Goswami,
  • Renee N. Donahue,
  • Julius Strauss,
  • Danielle M. Pastor,
  • Jason M. Redman,
  • Isaac Brownell,
  • Evrim B. Turkbey,
  • Seth M. Steinberg,
  • Lisa M. Cordes,
  • Jennifer L. Marté,
  • Maheen H. Khan,
  • Sheri McMahon,
  • Elizabeth Lamping,
  • Michell Manu,
  • Manuk Manukyan,
  • Douglas E. Brough,
  • Amy Lankford,
  • Caroline Jochems,
  • Jeffrey Schlom,
  • James L. Gulley

摘要

Background

This first-in-human phase 1 study (NCT04432597) evaluated the safety and recommended phase 2 dose (RP2D) of PRGN-2009, a gorilla adenoviral-vector targeting oncoproteins E6, E7 (human papillomavirus (HPV)16/18) and E5 (HPV16), as monotherapy (Arm 1A) and combined with the bifunctional TGF-β “trap”/anti-PD-L1 fusion protein bintrafusp alfa (BA; Arm 1B), in patients with recurrent/metastatic HPV-associated cancer.

Methods

Patients with ≥ 1 prior treatment (immunotherapy allowed) received PRGN-2009 (1 × 1011 particle units or 5 × 1011 particle units, subcutaneously) every 2 weeks for 3 doses, then every 4 weeks (Arm 1A), or PRGN-2009 (RP2D, schedule per Arm 1A) and BA (1200 mg, intravenously) every 2 weeks (Arm 1B). Primary endpoints were safety and RP2D of PRGN-2009; secondary objectives included overall response rate (ORR) and overall survival (OS).

Results

Seventeen patients were treated. In Arm 1A (n = 6) there were no dose limiting toxicities or grade 3/4 treatment-related adverse events (TRAEs), 5 × 1011 PU was selected as RP2D, no responses were observed, and median OS (mOS) was 7.4 months (95% CI 2.9–26.8). In Arm 1B (n = 11), grade 3/4 TRAEs occurred in 27% of patients, ORR was 20% for all patients (22% in checkpoint-resistant patients), and mOS was 24.6 months (95% CI 9.6-not reached). Multifunctional HPV-specific T cells were increased or induced de novo in 80% of patients and not impacted by anti-vector antibodies. Higher serum IL-8 at baseline associated with shorter OS.

Conclusions

PRGN-2009 was well tolerated, and immune responses were observed to PRGN-2009. Encouraging anti-tumor activity and OS were noted in the combination with BA arm, consisting mainly of checkpoint-resistant patients.

Trial Registration ClinicalTrials.gov Identifier: NCT04432597.