A. Naing , M. McKean , L.S. Rosen , D. Sommerhalder , N.M. Shaik , I.-M. Wang , C. Le Corre , K.A. Kern , N.H. Mishra , S.K. Pal
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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.</div></div><div><h3>Results</h3><div>Thirty-seven patients received treatment with PF-07209960 (1-, 3-, and 10-mg groups, <em>n</em> = 4 each; 15 mg, <em>n</em> = 3; 20 mg, <em>n</em> = 16; 30 mg, <em>n</em> = 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.</div></div><div><h3>Conclusion</h3><div>PF-07209960 was generally manageable, with potential antitumor activity in some patients.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 3","pages":"Article 104291"},"PeriodicalIF":8.3000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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\",\"authors\":\"A. Naing , M. McKean , L.S. Rosen , D. Sommerhalder , N.M. Shaik , I.-M. Wang , C. Le Corre , K.A. Kern , N.H. Mishra , S.K. Pal\",\"doi\":\"10.1016/j.esmoop.2025.104291\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>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.</div></div><div><h3>Materials and methods</h3><div>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.</div></div><div><h3>Results</h3><div>Thirty-seven patients received treatment with PF-07209960 (1-, 3-, and 10-mg groups, <em>n</em> = 4 each; 15 mg, <em>n</em> = 3; 20 mg, <em>n</em> = 16; 30 mg, <em>n</em> = 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. 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引用次数: 0
摘要
pf -07209960是一种抗体-细胞因子融合分子，由单效降低的白介素-15 （IL-15）突变蛋白和二价高亲和力的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）、药效学和潜在临床益处。材料和方法逐步递增剂量（1- 30mg）的PF-07209960皮下注射，每2周1次，28天为一个周期。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、抗PF-07209960的抗药物抗体（ADA）和中和抗体（NAb），以及使用RECIST 1.1版评估的肿瘤反应。结果37例患者接受PF-07209960（1、3、10 mg组）治疗，每组n = 4；15 mg, n = 3；20 mg, n = 16；30 mg, n = 6)。中位年龄为59.0岁（31-88岁）。6例（22.2%）患者有dlt。最常见的治疗相关ae (TRAEs)（≥50%）是一般疾病和给药部位状况[21例（56.8%）]和皮肤和皮下组织疾病[20例（54.1%）]。最常报道的≥3级TRAE是贫血[5(13.5%)]。两名微卫星稳定型结直肠癌患者证实部分缓解，分别来自PF-07209960 20 mg和30 mg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)，其中诱导组63.6%(21/33)，增强组30.3%（10/33）。结论pf -07209960总体可控，在部分患者中具有潜在的抗肿瘤活性。
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
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.
期刊介绍：
ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research.
ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO.
Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.
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