Division of Hematology and Oncology, UCLA David Geffen School of Medicine, Los Angeles, California.
Barts Cancer Centre, Barts Health NHS Trust, Queen Mary University of London, London, United Kingdom.
Clin Cancer Res. 2023 Nov 1;29(21):4373-4384. doi: 10.1158/1078-0432.CCR-23-0798.
The MORPHEUS platform was designed to identify early efficacy signals and evaluate the safety of novel immunotherapy combinations across cancer types. The phase Ib/II MORPHEUS-UC trial (NCT03869190) is evaluating atezolizumab plus magrolimab, niraparib, or tocilizumab in platinum-refractory locally advanced or metastatic urothelial carcinoma (mUC). Additional treatment combinations were evaluated and will be reported separately.
Patients had locally advanced or mUC that progressed during or following treatment with a platinum-containing regimen. The primary efficacy endpoint was investigator-assessed objective response rate (ORR). Key secondary endpoints included investigator-assessed progression-free survival (PFS) and overall survival (OS). Safety and exploratory biomarker analyses were also conducted.
Seventy-six patients were randomized to receive either atezolizumab plus magrolimab (n = 16), atezolizumab plus niraparib (n = 15), atezolizumab plus tocilizumab (n = 15), or atezolizumab monotherapy (control; n = 30). No additive benefit in ORR, PFS, or OS was seen in the treatment arms versus the control. The best confirmed ORR was 26.7% with atezolizumab plus magrolimab, 6.7% with atezolizumab plus niraparib, 20.0% with atezolizumab plus tocilizumab, and 27.6% with atezolizumab monotherapy. Overall, the treatment combinations were tolerable, and adverse events were consistent with each agent's known safety profile. Trends were observed for shrinkage of programmed death-ligand 1-positive tumors (atezolizumab, atezolizumab plus magrolimab, atezolizumab plus tocilizumab), inflamed tumors, or tumors with high mutational burden (atezolizumab), and immune excluded tumors (atezolizumab plus magrolimab).
The evaluated regimens in MORPHEUS-UC were tolerable. However, response rates for the combinations did not meet the criteria for further development in platinum-experienced locally advanced or mUC.
MORPHEUS 平台旨在识别早期疗效信号，并评估新型免疫疗法组合在多种癌症类型中的安全性。MORPHEUS-UC 试验（NCT03869190）的 Ib/II 期评估了阿替利珠单抗联合马吉妥昔单抗、尼拉帕利或托珠单抗治疗铂类难治性局部晚期或转移性尿路上皮癌（mUC）。其他治疗组合也进行了评估，将分别报告。
患者患有局部晚期或 mUC，在含铂方案治疗期间或之后进展。主要疗效终点为研究者评估的客观缓解率（ORR）。关键次要终点包括研究者评估的无进展生存期（PFS）和总生存期（OS）。还进行了安全性和探索性生物标志物分析。
76 名患者被随机分配接受阿替利珠单抗联合马吉妥昔单抗（n = 16）、阿替利珠单抗联合尼拉帕利（n = 15）、阿替利珠单抗联合托珠单抗（n = 15）或阿替利珠单抗单药治疗（对照组；n = 30）。与对照组相比，治疗组在 ORR、PFS 或 OS 方面没有额外获益。最佳确认 ORR 为阿替利珠单抗联合马吉妥昔单抗为 26.7%，阿替利珠单抗联合尼拉帕利为 6.7%，阿替利珠单抗联合托珠单抗为 20.0%，阿替利珠单抗单药治疗为 27.6%。总的来说，治疗组合是可耐受的，不良反应与每个药物的已知安全性特征一致。观察到程序性死亡配体 1 阳性肿瘤（阿替利珠单抗、阿替利珠单抗联合马吉妥昔单抗、阿替利珠单抗联合托珠单抗）、炎症肿瘤或高突变负担肿瘤（阿替利珠单抗）和免疫排除肿瘤（阿替利珠单抗联合马吉妥昔单抗）的缩小趋势。
MORPHEUS-UC 中评估的方案是可耐受的。然而，组合的缓解率没有达到在铂类经验丰富的局部晚期或 mUC 中进一步开发的标准。
