Atezolizumab Plus PEGPH20 Versus Chemotherapy in Advanced Pancreatic Ductal Adenocarcinoma and Gastric Cancer: MORPHEUS Phase Ib/II Umbrella Randomized Study Platform.
| Title: | Atezolizumab Plus PEGPH20 Versus Chemotherapy in Advanced Pancreatic Ductal Adenocarcinoma and Gastric Cancer: MORPHEUS Phase Ib/II Umbrella Randomized Study Platform. |
|---|---|
| Authors: | Ko AH; Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.; Kim KP; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.; Siveke JT; Department of Medical Oncology and Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK/DKFZ, partner site Essen), West German Cancer Center, University Hospital Essen, Essen, Germany.; Lopez CD; Division of Hematology Oncology, Oregon Health & Science University, Knight Cancer Institute, Portland, OR, USA.; Lacy J; Department of Medicine, Section of Medical Oncology, Yale School of Medicine, Yale University, New Haven, CT, USA.; O'Reilly EM; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Macarulla T; Gastrointestinal Cancer Unit, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.; Manji GA; Division of Hematology and Oncology, Columbia University Irving Medical Center, New York, NY, USA.; Lee J; Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.; Ajani J; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Alsina Maqueda M; Gastrointestinal Cancer Unit, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.; Rha SY; Department of Internal Medicine, Yonsei Cancer Center, Yonsei University Health System, Seoul, Republic of Korea.; Lau J; Genentech, Inc., South San Francisco, CA, USA.; Al-Sakaff N; F. Hoffmann-La Roche, Ltd, Basel, Switzerland.; Allen S; Genentech, Inc., South San Francisco, CA, USA.; Lu D; Hoffmann-La Roche Limited, Mississauga, ON, Canada.; Shemesh CS; Genentech, Inc., South San Francisco, CA, USA.; Gan X; Product Development Safety, Roche (China) Holding Ltd, Shanghai, People's Republic of China.; Cha E; Genentech, Inc., South San Francisco, CA, USA.; Oh DY; Department of Internal Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.; Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.; Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, Republic of Korea. |
| Source: | The oncologist [Oncologist] 2023 Jun 02; Vol. 28 (6), pp. 553-e472. |
| Publication Type: | Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Oxford University Press Country of Publication: England NLM ID: 9607837 Publication Model: Print Cited Medium: Internet ISSN: 1549-490X (Electronic) Linking ISSN: 10837159 NLM ISO Abbreviation: Oncologist Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2022- : Oxford : Oxford University Press; Original Publication: Dayton, Ohio : AlphaMed Press, c1996- |
| MeSH Terms: | Adenocarcinoma*/drug therapy ; Carcinoma, Pancreatic Ductal*/drug therapy ; Pancreatic Neoplasms*/drug therapy ; Pancreatic Neoplasms*/pathology ; Stomach Neoplasms*/drug therapy; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Hyaluronoglucosaminidase/adverse effects ; Paclitaxel/adverse effects ; Humans ; Antibodies, Monoclonal, Humanized |
| Abstract: | 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).; (© The Author(s) 2023. Published by Oxford University Press.) |
| References: | J Natl Compr Canc Netw. 2022 Feb;20(2):167-192. (PMID: 35130500); J Natl Compr Canc Netw. 2021 Apr 1;19(4):439-457. (PMID: 33845462); J Clin Oncol. 2018 Feb 1;36(4):359-366. (PMID: 29232172); J Clin Oncol. 2020 Sep 20;38(27):3185-3194. (PMID: 32706635); J Exp Clin Cancer Res. 2021 Sep 10;40(1):286. (PMID: 34507591); Clin Cancer Res. 2015 Aug 1;21(15):3561-8. (PMID: 25695692); Clin Transl Sci. 2022 Jan;15(1):130-140. (PMID: 34432389); Front Oncol. 2021 Jul 15;11:688377. (PMID: 34336673); J Hematol Oncol. 2019 Sep 5;12(1):92. (PMID: 31488176); CA Cancer J Clin. 2020 Sep;70(5):375-403. (PMID: 32683683) |
| Grant Information: | P30 CA008748 United States CA NCI NIH HHS; UL1 TR001863 United States TR NCATS NIH HHS |
| Contributed Indexing: | Keywords: PD-L1; basket study; combination therapy; gastric cancer; hyaluronan; immunotherapy; pancreatic cancer; proof of concept |
| Molecular Sequence: | ClinicalTrials.gov NCT03281369; NCT03193190 |
| Substance Nomenclature: | EC 3.2.1.35 (Hyaluronoglucosaminidase); P88XT4IS4D (Paclitaxel); 52CMI0WC3Y (atezolizumab); 0 (Antibodies, Monoclonal, Humanized); EC 3.2.1.35 (PEGPH20) |
| Entry Date(s): | Date Created: 20230320 Date Completed: 20230608 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10243783 |
| DOI: | 10.1093/oncolo/oyad022 |
| PMID: | 36940261 |
| Database: | MEDLINE |
Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't