Fred Hutchinson Cancer Center, University of Washington, Seattle, WA.
Department of Medical Oncology & Clinical Research Unit, Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse (IUCT-Oncopôle), Toulouse, France.
J Clin Oncol. 2024 Apr 20;42(12):1415-1425. doi: 10.1200/JCO.22.02835. Epub 2024 Jan 23.
Pembrolizumab is standard therapy for patients with metastatic urothelial cancer (mUC) who progress after first-line platinum-based chemotherapy; however, only approximately 21% of patients respond. Sacituzumab govitecan (SG) is a trophoblast cell surface antigen-2-directed antibody-drug conjugate with US Food and Drug Administration-accelerated approval to treat patients with locally advanced or mUC who previously received platinum-based chemotherapy and a checkpoint inhibitor (CPI). Here, we report the primary analysis of TROPHY-U-01 cohort 3.
TROPHY-U-01 (ClinicalTrials.gov identifier: NCT03547973) is a multicohort, open-label phase II study. Patients were CPI-naïve and had mUC progression after platinum-based chemotherapy in the metastatic setting or ≤12 months in the (neo)adjuvant setting. Patients received 10 mg/kg of SG once on days 1 and 8 and 200 mg of pembrolizumab once on day 1 of 21-day cycles. The primary end point was objective response rate (ORR) per central review. Secondary end points included clinical benefit rate (CBR), duration of response (DOR) and progression-free survival (PFS) per central review, and safety.
Cohort 3 included 41 patients (median age 67 years; 83% male; 78% visceral metastases [29% liver]). With a median follow-up of 14.8 months, the ORR was 41% (95% CI, 26.3 to 57.9; 20% complete response rate), CBR was 46% (95% CI, 30.7 to 62.6), median DOR was 11.1 months (95% CI, 4.8 to not estimable [NE]), and median PFS was 5.3 months (95% CI, 3.4 to 10.2). The median overall survival was 12.7 months (range, 10.7-NE). Grade ≥3 treatment-related adverse events occurred in 61% of patients; most common were neutropenia (37%), leukopenia (20%), and diarrhea (20%).
SG plus pembrolizumab demonstrated a high response rate with an overall manageable toxicity profile in patients with mUC who progressed after platinum-based chemotherapy. No new safety signals were detected. These data support further evaluation of SG plus CPI in mUC.
派姆单抗是一线铂类化疗后进展的转移性尿路上皮癌（mUC）患者的标准治疗方法；然而，只有约 21%的患者有反应。Sacituzumab govitecan（SG）是一种滋养细胞表面抗原-2 定向抗体药物偶联物，获得了美国食品和药物管理局的加速批准，用于治疗先前接受过铂类化疗和检查点抑制剂（CPI）治疗的局部晚期或 mUC 患者。在这里，我们报告了 TROPHY-U-01 队列 3 的主要分析结果。
TROPHY-U-01（临床试验标识符：NCT03547973）是一项多队列、开放标签的 2 期研究。患者为 CPI 初治，且在转移性环境中铂类化疗后进展，或在（新）辅助环境中进展≤12 个月。患者接受 10mg/kg 的 SG 一次，在第 1 和 8 天，200mg 的 pembrolizumab 一次，在第 1 天，每 21 天为一个周期。主要终点是中心评估的客观缓解率（ORR）。次要终点包括中心评估的临床获益率（CBR）、缓解持续时间（DOR）和无进展生存期（PFS），以及安全性。
队列 3 包括 41 名患者（中位年龄 67 岁；83%为男性；78%有内脏转移[29%有肝脏转移]）。中位随访 14.8 个月时，ORR 为 41%（95%CI，26.3 至 57.9；20%完全缓解率），CBR 为 46%（95%CI，30.7 至 62.6），中位 DOR 为 11.1 个月（95%CI，4.8 至不可估计[NE]），中位 PFS 为 5.3 个月（95%CI，3.4 至 10.2）。中位总生存期为 12.7 个月（范围，10.7-NE）。61%的患者发生了≥3 级治疗相关不良事件；最常见的是中性粒细胞减少（37%）、白细胞减少（20%）和腹泻（20%）。
在铂类化疗后进展的 mUC 患者中，SG 加 pembrolizumab 显示出高缓解率，总体毒性可管理。未发现新的安全性信号。这些数据支持进一步评估 SG 加 CPI 在 mUC 中的应用。
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