卡博替尼和纳武单抗单独或与伊匹单抗联合治疗晚期/转移性泌尿生殖肿瘤的 I 期试验和扩展队列的最终结果。
Final Results From a Phase I Trial and Expansion Cohorts of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced/Metastatic Genitourinary Tumors.
发表日期：2024 Jul 02
作者：
Andrea B Apolo, Daniel M Girardi, Scot A Niglio, Rosa Nadal, Andre R Kydd, Nicholas Simon, Lisa Ley, Lisa M Cordes, Elias Chandran, Seth M Steinberg, Sunmin Lee, Min-Jung Lee, Shraddha Rastogi, Nahoko Sato, Liang Cao, A Rouf Banday, Salah Boudjadi, Maria J Merino, Antoun Toubaji, Dilara Akbulut, Bernadette Redd, Hadi Bagheri, Rene Costello, Sandeep Gurram, Piyush K Agarwal, Heather J Chalfin, Vladimir Valera, Howard Streicher, John Joseph Wright, Elad Sharon, William D Figg, Howard L Parnes, James L Gulley, Biren Saraiya, Sumanta K Pal, David Quinn, Mark N Stein, Primo N Lara, Donald P Bottaro, Amir Mortazavi
来源：
MOLECULAR & CELLULAR PROTEOMICS
摘要：
卡博替尼和纳武单抗 (CaboNivo) 单独使用或联合伊匹单抗 (CaboNivoIpi) 在剂量递增阶段对转移性尿路上皮癌 (mUC)、转移性肾细胞癌 (mRCC) 和罕见泌尿生殖 (GU) 肿瘤患者显示出良好的疗效和安全性我学习。我们报告了 I 期患者和七个扩展队列的安全性、总体缓解率 (ORR)、无进展生存期 (PFS) 和总体生存期 (OS) 的最终数据分析。这是一项由研究者发起的、多中心、第一阶段试验。 CaboNivo 双峰扩展队列包括 (1) mUC、(2) mRCC 和 (3) 膀胱/脐尿管腺癌； CaboNivoIpi 三联体扩展队列包括 (1) mUC、(2) mRCC、(3) 阴茎癌和 (4) 膀胱鳞状细胞癌和其他罕见 GU 肿瘤（ClinicalTrials.gov 标识符：NCT02496208）。该研究招募了 120 名患者使用 CaboNivo (n = 64) 或 CaboNivoIpi (n = 56) 治疗，中位随访时间为 49.2 个月。在 108 名可评估患者（CaboNivo n = 59；CaboNivoIpi n = 49）中，ORR 为 38%（完全缓解率为 11%），中位缓解持续时间为 20 个月。 mUC 的 ORR 为 42.4%，mRCC (n = 16) 为 62.5%，膀胱鳞状细胞癌 (n = 7) 为 85.7%，阴茎癌 (n = 9) 为 44.4%，肾髓质为 50.0%癌 (n = 2)。 84% 的 CaboNivo 患者和 80% 的 CaboNivoIpi 患者发生≥ 3 级治疗相关不良事件。CaboNivo 和 CaboNivoIpi 在多种 GU 恶性肿瘤患者中表现出临床活性和安全性，特别是透明细胞肾细胞癌、尿路上皮癌和罕见 GU 肿瘤，如如膀胱鳞状细胞癌、膀胱小细胞癌、膀胱腺癌、肾髓质癌和阴茎癌。
Cabozantinib and nivolumab (CaboNivo) alone or with ipilimumab (CaboNivoIpi) have shown promising efficacy and safety in patients with metastatic urothelial carcinoma (mUC), metastatic renal cell carcinoma (mRCC), and rare genitourinary (GU) tumors in a dose-escalation phase I study. We report the final data analysis of the safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the phase I patients and seven expansion cohorts.This is an investigator-initiated, multicenter, phase I trial. CaboNivo doublet expansion cohorts included (1) mUC, (2) mRCC, and (3) adenocarcinoma of the bladder/urachal; CaboNivoIpi triplet expansion cohorts included (1) mUC, (2) mRCC, (3) penile cancer, and (4) squamous cell carcinoma of the bladder and other rare GU tumors (ClinicalTrials.gov identifier: NCT02496208).The study enrolled 120 patients treated with CaboNivo (n = 64) or CaboNivoIpi (n = 56), with a median follow-up of 49.2 months. In 108 evaluable patients (CaboNivo n = 59; CaboNivoIpi n = 49), the ORR was 38% (complete response rate 11%) and the median duration of response was 20 months. The ORR was 42.4% for mUC, 62.5% for mRCC (n = 16), 85.7% for squamous cell carcinoma of the bladder (n = 7), 44.4% for penile cancer (n = 9), and 50.0% for renal medullary carcinoma (n = 2). Grade ≥ 3 treatment-related adverse events occurred in 84% of CaboNivo patients and 80% of CaboNivoIpi patients.CaboNivo and CaboNivoIpi demonstrated clinical activity and safety in patients with multiple GU malignancies, especially clear cell RCC, urothelial carcinoma, and rare GU tumors such as squamous cell carcinoma of the bladder, small cell carcinoma of the bladder, adenocarcinoma of the bladder, renal medullary carcinoma, and penile cancer.