图卡替尼联合曲妥珠单抗治疗既往接受过治疗的人表皮生长因子受体 2 阳性转移性胆道癌（SGNTUC-019）：一项 II 期篮子研究。

Tucatinib and Trastuzumab for Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Metastatic Biliary Tract Cancer (SGNTUC-019): A Phase II Basket Study.

机构信息

National Cancer Center Hospital East, Kashiwa, Japan.

Aichi Cancer Center Hospital, Nagoya, Japan.

出版信息

J Clin Oncol. 2023 Dec 20;41(36):5569-5578. doi: 10.1200/JCO.23.00606. Epub 2023 Sep 26.

PURPOSE

To evaluate the efficacy and safety of tucatinib and trastuzumab in patients with previously treated human epidermal growth factor receptor 2-positive (HER2+) metastatic biliary tract cancer (mBTC).

METHODS

SGNTUC-019 (ClinicalTrials.gov identifier: NCT04579380) is an open-label phase II basket study evaluating the efficacy and safety of tucatinib and trastuzumab in patients with HER2-altered solid tumors. In the biliary tract cancer cohort, patients had previously treated HER2 overexpressing or amplified (HER2+) tumors (identified with local testing) with no prior HER2-directed therapy. The primary end point was confirmed objective response rate (cORR) per investigator assessment. Patients were treated on a 21-day cycle with tucatinib (300 mg orally twice daily) and trastuzumab (8 mg/kg intravenously followed by 6 mg/kg every 3 weeks).

RESULTS

Thirty patients were enrolled. As of data cutoff (January 30, 2023), the median duration of follow-up was 10.8 months. The cORR was 46.7% (90% CI, 30.8 to 63.0), with a disease control rate of 76.7% (90% CI, 60.6 to 88.5). The median duration of response and progression-free survival were 6.0 months (90% CI, 5.5 to 6.9) and 5.5 months (90% CI, 3.9 to 8.1), respectively. At data cutoff, 15 patients (50.0%) had died, and the estimated 12-month overall survival rate was 53.6% (90% CI, 36.8 to 67.8). The two most common treatment-emergent adverse events (TEAEs) were pyrexia (43.3%) and diarrhea (40.0%). Grade ≥3 TEAEs were reported in 18 patients (60.0%), with the most common being cholangitis, decreased appetite, and nausea (all 10.0%), which were generally not treatment related. TEAEs led to treatment regimen discontinuation in one patient, and there were no deaths due to TEAEs.

CONCLUSION

Tucatinib combined with trastuzumab had clinically significant antitumor activity and was well tolerated in patients with previously treated HER2+ mBTC.

目的

评估曲妥珠单抗联合 Tucatinib 治疗既往接受过治疗的人表皮生长因子受体 2 阳性（HER2+）转移性胆道癌（mBTC）患者的疗效和安全性。

方法

SGNTUC-019（ClinicalTrials.gov 标识符：NCT04579380）是一项开放标签的 II 期篮子研究，评估 Tucatinib 联合曲妥珠单抗在 HER2 改变的实体瘤患者中的疗效和安全性。在胆道癌队列中，患者既往接受过局部检测显示过表达或扩增（HER2+）肿瘤（HER2 靶向治疗前）。主要终点为研究者评估的确认客观缓解率（cORR）。患者每 21 天接受一次治疗，方案为 Tucatinib（300 mg，每日口服 2 次）联合曲妥珠单抗（8 mg/kg 静脉注射，随后每 3 周 6 mg/kg）。

结果

共纳入 30 例患者。截至数据截止日期（2023 年 1 月 30 日），中位随访时间为 10.8 个月。cORR 为 46.7%（90%CI，30.8 至 63.0），疾病控制率为 76.7%（90%CI，60.6 至 88.5）。中位缓解持续时间和无进展生存期分别为 6.0 个月（90%CI，5.5 至 6.9）和 5.5 个月（90%CI，3.9 至 8.1）。截至数据截止日期，15 例患者（50.0%）死亡，估计 12 个月总生存率为 53.6%（90%CI，36.8 至 67.8）。最常见的两种治疗相关不良事件（TEAEs）为发热（43.3%）和腹泻（40.0%）。18 例患者（60.0%）报告了≥3 级 TEAEs，最常见的为胆管炎、食欲下降和恶心（均为 10.0%），均与治疗不相关。TEAEs 导致 1 例患者停止治疗方案，无 TEAEs 导致死亡。