Atezolizumab + PEGPH20与化疗治疗晚期胰管腺癌和胃癌：MORPHEUS Ib/II伞式随机研究平台。
Atezolizumab Plus PEGPH20 Versus Chemotherapy in Advanced Pancreatic Ductal Adenocarcinoma and Gastric Cancer: MORPHEUS Phase Ib/II Umbrella Randomized Study Platform.
发表日期：2023 Mar 20
作者：
Andrew H Ko, Kyu-Pyo Kim, Jens T Siveke, Charles D Lopez, Jill Lacy, Eileen M O'Reilly, Teresa Macarulla, Gulam A Manji, Jeeyun Lee, Jaffer Ajani, Maria Alsina Maqueda, Sun-Young Rha, Janet Lau, Nedal Al-Sakaff, Simon Allen, Danny Lu, Colby S Shemesh, Xinxin Gan, Edward Cha, Do-Youn Oh
来源：
Cell Death & Disease
摘要：
MORPHEUS平台包含多个开放标签、随机、Ib/II期试验，旨在确定治疗组合在各种癌症中的早期疗效和安全信号。其中，评估了atezolizumab（抗程序性细胞死亡配体1 [PD-L1]）与PEG化重组人透明质酸酶（PEGPH20）的联合应用。在两个随机的MORPHEUS试验中，符合条件的晚期、曾接受治疗的胰腺导管腺癌（PDAC）或胃癌（GC）患者接受了atezolizumab加PEGPH20或对照治疗（mFOLFOX6或gemcitabine加nab-紫杉醇[MORPHEUS-PDAC];ramucirumab加紫杉醇[MORPHEUS-GC]）。主要终点为RECIST 1.1的客观缓解率（ORR）和安全性。在MORPHEUS-PDAC中，atezolizumab加PEGPH20组（n=66）的ORR为6.1%（95% CI，1.68%-14.80%），化疗组（n=42）的ORR为2.4%（95% CI，0.06%-12.57%）。在各自的组中，65.2%和61.9%的患者出现了3/4级的不良事件（AEs）；4.5%和2.4%的患者出现了5级AEs。在MORPHEUS-GC中，atezolizumab加PEGPH20组的确认ORR（n=13）为0%（95% CI，0%-24.7%），对照组的ORR为16.7%（95% CI，2.1%-48.4%；n=12）。相应的，30.8%和75.0%的患者出现了3/4级的AEs，没有发生5级AEs。在PDAC患者中，atezolizumab加PEGPH20表现出有限的临床活性，在GC患者中则没有临床活性。atezolizumab加PEGPH20的安全性与各自单药的已知安全资料一致。 （ClinicalTrials.gov标识符：NCT03193190和NCT03281369）。©作者（们）2023。由牛津大学出版社出版。
The MORPHEUS platform comprises multiple open-label, randomized, phase Ib/II trials designed to identify early efficacy and safety signals of treatment combinations across cancers. Atezolizumab (anti-programmed cell death 1 ligand 1 [PD-L1]) was evaluated in combination with PEGylated recombinant human hyaluronidase (PEGPH20).In 2 randomized MORPHEUS trials, eligible patients with advanced, previously treated pancreatic ductal adenocarcinoma (PDAC) or gastric cancer (GC) received atezolizumab plus PEGPH20, or control treatment (mFOLFOX6 or gemcitabine plus nab-paclitaxel [MORPHEUS-PDAC]; ramucirumab plus paclitaxel [MORPHEUS-GC]). Primary endpoints were objective response rates (ORR) per RECIST 1.1 and safety.In MORPHEUS-PDAC, ORRs with atezolizumab plus PEGPH20 (n = 66) were 6.1% (95% CI, 1.68%-14.80%) vs. 2.4% (95% CI, 0.06%-12.57%) with chemotherapy (n = 42). In the respective arms, 65.2% and 61.9% had grade 3/4 adverse events (AEs); 4.5% and 2.4% had grade 5 AEs. In MORPHEUS-GC, confirmed ORRs with atezolizumab plus PEGPH20 (n = 13) were 0% (95% CI, 0%-24.7%) vs. 16.7% (95% CI, 2.1%-48.4%) with control (n = 12). Grade 3/4 AEs occurred in 30.8% and 75.0% of patients, respectively; no grade 5 AEs occurred.Atezolizumab plus PEGPH20 showed limited clinical activity in patients with PDAC and none in patients with GC. The safety of atezolizumab plus PEGPH20 was consistent with each agent's known safety profile. (ClinicalTrials.gov Identifier: NCT03193190 and NCT03281369).© The Author(s) 2023. Published by Oxford University Press.