一项评估PF-07209960在晚期或转移性实体瘤患者中的安全性、耐受性、药代动力学、药效学、免疫原性和抗肿瘤活性的首次人体I期研究。

First-in-human phase I study to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity of PF-07209960 in patients with advanced or metastatic solid tumors.

作者信息

Naing A, McKean M, Rosen L S, Sommerhalder D, Shaik N M, Wang I-M, Le Corre C, Kern K A, Mishra N H, Pal S K

机构信息

Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, USA.

Sarah Cannon Research Institute (SCRI), Nashville, USA.

出版信息

ESMO Open. 2025 Mar;10(3):104291. doi: 10.1016/j.esmoop.2025.104291. Epub 2025 Feb 17.

DOI:10.1016/j.esmoop.2025.104291

PMID:39965362

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11876874/

Abstract

BACKGROUND

PF-07209960 is an antibody-cytokine fusion molecule that consists of a single potency-reduced interleukin-15 (IL-15) mutein and a bivalent high-affinity anti-programmed cell death protein 1 (PD-1) full-length IgG. This phase I study (NCT04628780) evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and potential clinical benefits of PF-07209960 in patients with selected locally advanced or metastatic solid tumors for whom no standard therapy was available.

MATERIALS AND METHODS

Escalating doses (1-30 mg) of PF-07209960 were administered subcutaneously once every 2 weeks in 28-day cycles. The primary endpoints included dose-limiting toxicities (DLTs), adverse events (AEs), and laboratory abnormalities. The secondary endpoints included PK, anti-drug antibodies (ADA) and neutralizing antibodies (NAb) against PF-07209960, and tumor response assessed using RECIST version 1.1.

RESULTS

Thirty-seven patients received treatment with PF-07209960 (1-, 3-, and 10-mg groups, n = 4 each; 15 mg, n = 3; 20 mg, n = 16; 30 mg, n = 6). The median age was 59.0 years (range 31-88 years). Six (22.2%) patients had DLTs. The most frequently reported treatment-related AEs (TRAEs) (≥50%) were general disorders and administration site condition [21 (56.8%)] and skin and subcutaneous tissue disorders [20 (54.1%)]. The most frequently reported grade ≥3 TRAE was anemia [5 (13.5%)]. Two patients with microsatellite-stable colorectal cancer had confirmed partial response, one each from the PF-07209960 20-mg and 30-mg cohorts, with a duration of response of 9.5 and 3 months, respectively. The rate of ADA was 93.9% (31/33), of which 63.6% (21/33) was treatment induced and 30.3% (10/33) was treatment boosted.

CONCLUSION

PF-07209960 was generally manageable, with potential antitumor activity in some patients.

摘要

背景

PF-07209960是一种抗体-细胞因子融合分子，由单一效力降低的白细胞介素-15（IL-15）突变体和二价高亲和力抗程序性细胞死亡蛋白1（PD-1）全长IgG组成。这项I期研究（NCT04628780）评估了PF-07209960在无可用标准治疗的局部晚期或转移性实体瘤患者中的安全性、耐受性、药代动力学（PK）、药效学及潜在临床益处。

材料与方法

以28天为一个周期，每2周皮下注射一次递增剂量（1-30毫克）的PF-07209960。主要终点包括剂量限制性毒性（DLT）、不良事件（AE）和实验室异常。次要终点包括PK、针对PF-07209960的抗药抗体（ADA）和中和抗体（NAb），以及使用实体瘤疗效评价标准（RECIST）1.1版评估的肿瘤反应。

结果

37例患者接受了PF-07209960治疗（1毫克、3毫克和10毫克组各4例；15毫克组3例；20毫克组16例；30毫克组6例）。中位年龄为59.0岁（范围31-88岁）。6例（22.2%）患者出现DLT。最常报告的治疗相关不良事件（TRAE）（≥50%）为全身疾病和给药部位情况[21例（56.8%）]以及皮肤和皮下组织疾病[20例（54.1%）]。最常报告的≥3级TRAE为贫血[5例（13.5%）]。2例微卫星稳定的结直肠癌患者确认部分缓解，分别来自PF-07209960 20毫克和30毫克队列，缓解持续时间分别为9.5个月和3个月。ADA发生率为93.9%（31/33），其中63.6%（21/33）是治疗诱导的，30.3%（10/33）是治疗增强的。