Trastuzumab Deruxtecan With Nivolumab in HER2-Expressing Metastatic Breast or Urothelial Cancer: Analysis of the Phase Ib DS8201-A-U105 Study

IF 10 1区医学 Q1 ONCOLOGY

Clinical Cancer Research Pub Date : 2024-10-15 DOI:10.1158/1078-0432.ccr-24-1513

Erika Hamilton, Matthew D. Galsky, Sebastian Ochsenreither, Gianluca Del Conte, Miguel Martín, Maria José. de Miguel, Evan Y. Yu, Anja Williams, Maria Gion, Antoinette R. Tan, Laila Agrawal, Annemie Rutten, Jean-Pascal Machiels, Sara Cresta, Philip R. Debruyne, Audrey Hennequin, Victor Moreno, Anna Minchom, Frances Valdes-Albini, Daniel Petrylak, Li Li, Zenta Tsuchihashi, Fumitaka Suto, Fu-Chih Cheng, Maha Kandil, Daniel Barrios, Sara Hurvitz

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引用次数: 0

Abstract

Purpose: This multicenter phase Ib study investigated trastuzumab deruxtecan (T-DXd) plus nivolumab in patients with HER2-expressing metastatic breast cancer (mBC) and metastatic urothelial cancer (mUC). Patients and Methods: Part 1 determined the recommended dose for expansion (RDE) of T-DXd plus nivolumab. Part 2 evaluated efficacy and safety; the primary endpoint was confirmed objective response rate (cORR) by independent central review. Results: Seven patients with mBC were enrolled in part 1 and received T-DXd 3.2 mg/kg (4 patients) or 5.4 mg/kg (3 patients) plus nivolumab. The RDE for T-DXd was 5.4 mg/kg plus nivolumab 360 mg intravenously/3 weeks. In part 2, 32 patients with HER2-positive mBC (cohort 1; inclusive of 3 administered 5.4 mg/kg in part 1), 16 with HER2-low mBC (cohort 2), 30 with HER2-high mUC (cohort 3), and 4 with HER2-low mUC (cohort 4) were enrolled. At data cutoff (July 22, 2021), the cORR (95% CI) for cohorts 1-4 was 65.6% (46.8%-81.4%), 50.0% (24.7%-75.3%), 36.7% (19.9%-56.1%), and not assessed due to small sample size, respectively. Median treatment duration (range) with T-DXd in cohorts 1-4 was 8.9 (1-23), 6.9 (1-21), 3.9 (1-21) months, and not assessed; most common treatment-emergent adverse event was nausea (55.2%, 62.5%, 73.3%, 75.0%). Adjudicated drug-related ILD/pneumonitis rates (cohorts 1-3) were 20.7%, 0%, and 20.0% (1 grade 5 each, cohorts 1 and 3). Conclusion: T-DXd plus nivolumab demonstrated promising antitumor activity in HER2-expressing mBC or mUC and safety consistent with the known profile of T‑DXd. ILD/pneumonitis is an important risk and requires careful monitoring and prompt intervention.

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曲妥珠单抗德鲁司坦联合尼妥珠单抗治疗 HER2 表达的转移性乳腺癌或泌尿道癌：Ib期DS8201-A-U105研究分析

目的：这项多中心Ib期研究探讨了曲妥珠单抗德鲁司坦（T-DXd）联合尼妥珠单抗治疗HER2表达的转移性乳腺癌（mBC）和转移性尿路上皮癌（mUC）患者。患者和方法：第一部分确定了T-DXd加尼夫单抗的推荐扩大剂量（RDE）。第二部分评估疗效和安全性；主要终点是经独立中央审查确认的客观反应率（cORR）。研究结果第1部分共纳入了7名mBC患者，他们接受了T-DXd 3.2 mg/kg（4名患者）或5.4 mg/kg（3名患者）加nivolumab治疗。T-DXd 的 RDE 为 5.4 mg/kg 加 nivolumab 360 mg 静脉注射/3 周。在第 2 部分中，共招募了 32 名 HER2 阳性 mBC 患者（第 1 组；包括在第 1 部分中接受 5.4 mg/kg 治疗的 3 名患者）、16 名 HER2 低的 mBC 患者（第 2 组）、30 名 HER2 高的 mUC 患者（第 3 组）和 4 名 HER2 低的 mUC 患者（第 4 组）。在数据截止日（2021 年 7 月 22 日），队列 1-4 的 cORR（95% CI）分别为 65.6% (46.8%-81.4%)、50.0% (24.7%-75.3%)、36.7% (19.9%-56.1%)，由于样本量较小，未进行评估。1-4组患者使用T-DXd的中位治疗时间（范围）分别为8.9（1-23）、6.9（1-21）、3.9（1-21）个月和未评估；最常见的治疗突发不良事件是恶心（55.2%、62.5%、73.3%、75.0%）。裁定的药物相关 ILD/肺炎发生率（1-3 组）分别为 20.7%、0% 和 20.0%（1 组和 3 组各有 1 例 5 级）。结论T-DXd 加 nivolumab 对表达 HER2 的 mBC 或 mUC 具有良好的抗肿瘤活性，其安全性与 T-DXd 的已知特征一致。ILD/肺炎是一个重要风险，需要仔细监测和及时干预。

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来源期刊

Clinical Cancer Research 医学-肿瘤学

CiteScore

20.10

自引率

1.70%

发文量

1207

审稿时长

2.1 months

期刊介绍： Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.