阿替利珠单抗联合 PEGPH20 与化疗治疗晚期胰腺导管腺癌和胃癌：MORPHEUS 期 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.

机构信息

Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

出版信息

Oncologist. 2023 Jun 2;28(6):553-e472. doi: 10.1093/oncolo/oyad022.

BACKGROUND

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).

METHODS

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.

RESULTS

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.

CONCLUSION

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).

背景

MORPHEUS 平台由多个开放性、随机、Ib/II 期试验组成，旨在确定癌症治疗组合的早期疗效和安全性信号。阿替利珠单抗（抗程序性细胞死亡配体 1 [PD-L1]）与聚乙二醇化重组人透明质酸酶（PEGPH20）联合评估。

方法

在 2 项随机 MORPHEUS 试验中，符合条件的晚期、既往治疗的胰腺导管腺癌（PDAC）或胃癌（GC）患者接受阿替利珠单抗加 PEGPH20 或对照治疗（mFOLFOX6 或吉西他滨加 nab-紫杉醇[MORPHEUS-PDAC]；雷莫芦单抗加紫杉醇 [MORPHEUS-GC]）。主要终点为根据 RECIST 1.1 评估的客观缓解率（ORR）和安全性。

结果

在 MORPHEUS-PDAC 中，阿替利珠单抗加 PEGPH20 组（n=66）的 ORR 为 6.1%（95%CI，1.68%-14.80%），而化疗组（n=42）为 2.4%（95%CI，0.06%-12.57%）。在相应的臂中，65.2%和 61.9%的患者发生 3/4 级不良事件（AE）；4.5%和 2.4%的患者发生 5 级 AE。在 MORPHEUS-GC 中，阿替利珠单抗加 PEGPH20 组（n=13）的确认 ORR 为 0%（95%CI，0%-24.7%），而对照组（n=12）为 16.7%（95%CI，2.1%-48.4%）。分别有 30.8%和 75.0%的患者发生 3/4 级 AE，均无 5 级 AE。